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  • 1.
    Schwartz, Gregory G.
    et al.
    Vet Affairs Med Ctr, CO 80220 USA; Univ Colorado, CO USA.
    Ballantyne, Christie M.
    Baylor Coll Med, TX 77030 USA.
    Barter, Philip J.
    Univ New South Wales, Australia.
    Kallend, David
    Medicines Co, Switzerland.
    Leiter, Lawrence A.
    Univ Toronto, Canada.
    Leitersdorf, Eran
    Hadassah Hebrew Univ, Israel.
    McMurray, John J. V.
    Univ Glasgow, Scotland.
    Nicholls, Stephen J.
    Univ Adelaide, Australia.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Shah, Prediman K.
    Cedars Sinai Heart Inst, CA USA.
    Tardif, Jean-Claude
    Univ Montreal, Canada.
    Kittelson, John
    Univ Colorado, CO USA.
    Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following Acute Coronary Syndrome Analysis of the dal-Outcomes Randomized Clinical Trial2018Ingår i: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 3, nr 2, s. 164-168Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IMPORTANCE It is uncertain whether lipoprotein(a) [Lp(a)], which is associated with incident cardiovascular disease, is an independent risk factor for recurrent cardiovascular events after acute coronary syndrome (ACS). OBJECTIVE To determine the association of Lp(a) concentration measured after ACS with the subsequent risk of ischemic cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS This nested case-cohort analysis was performed as an ad hoc analysis of the dal-Outcomes randomized clinical trial. This trial compared dalcetrapib, the cholesteryl ester transfer protein inhibitor, with placebo in patients with recent ACS and was performed between April 2008 and September 2012 at 935 sites in 27 countries. There were 969 case patients who experienced a primary cardiovascular outcome, and there were 3170 control patients who were event free at the time of a case event and had the same type of index ACS (unstable angina ormyocardial infarction) as that of the respective case patients. Concentration of Lp(a) was measured by immunoturbidimetric assay. Data analysis for this present study was conducted from June 8, 2016, to April 21, 2017. INTERVENTIONS Patients were randomly assigned to receive treatment with dalcetrapib, 600 mg daily, or matching placebo, beginning 4 to 12 weeks after ACS. MAIN OUTCOMES AND MEASURES Death due to coronary heart disease, a major nonfatal coronary event (myocardial infarction, hospitalization for unstable angina, or resuscitated cardiac arrest), or fatal or nonfatal ischemic stroke. RESULTS The mean (SD) age was 63 (10) years for the 969 case patients and 60 (9) years for the 3170 control patients, and both cohorts were composed of predominantly male (770 case patients [79%] and 2558 control patients [81%]; P = .40) and white patients (858 case patients [89%] and 2825 control patients [89%]; P = .62). At baseline, the median (interquartile range) Lp(a) level was 12.3 (4.7-50.9) mg/dL. There was broad application of evidence-based secondary prevention strategies after ACS, including use of statins in 4030 patients (97%). The cumulative distribution of baseline Lp(a) levels did not differ between cases and controls at P = .16. Case-cohort regression analysis showed no association of baseline Lp(a) level with risk of cardiovascular events. For a doubling of Lp(a) concentration, the hazard ratio (case to control) was 1.01 (95% CI, 0.96-1.06; P = .66) after adjustment for 16 baseline variables, including assigned study treatment. CONCLUSIONS AND RELEVANCE For patients with recent ACS who are treated with statins, Lp(a) concentration was not associated with adverse cardiovascular outcomes. These findings call into question whether treatment specifically targeted to reduce Lp(a) levels would thereby lower the risk for ischemic cardiovascular events after ACS.

  • 2.
    Willeit, Peter
    et al.
    Med Univ Innsbruck, Austria; Univ Cambridge, England.
    Ridker, Paul M.
    Harvard Med Sch, MA USA.
    Nestel, Paul J.
    Baker Heart and Diabet Inst, Australia.
    Simes, John
    Univ Sydney, Australia.
    Tonkin, Andrew M.
    Monash Univ, Australia.
    Pedersen, Terje R.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Schwartz, Gregory G.
    VA Med Ctr, CO USA; Univ Colorado, CO USA.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Colhoun, Helen M.
    MRC Inst Genet and Mol Med, Scotland.
    Kronenberg, Florian
    Med Univ Innsbruck, Austria.
    Drechsler, Christiane
    Univ Hniv Hosp Wurzburg, Germany.
    Wanner, Christoph
    Univ Hosp Wurzburg, Germany.
    Mora, Samia
    Harvard Med Sch, MA USA.
    Lesogor, Anastasia
    Novartis Pharma AG, Switzerland.
    Tsimikas, Sotirios
    Univ Calif San Diego, CA 92093 USA.
    Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials2018Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, nr 10155, s. 1311-1320Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Elevated lipoprotein(a) is a genetic risk factor for cardiovascular disease in general population studies. However, its contribution to risk for cardiovascular events in patients with established cardiovascular disease or on statin therapy is uncertain. Methods Patient-level data from seven randomised, placebo-controlled, statin outcomes trials were collated and harmonised to calculate hazard ratios (HRs) for cardiovascular events, defined as fatal or non-fatal coronary heart disease, stroke, or revascularisation procedures. HRs for cardiovascular events were estimated within each trial across predefined lipoprotein(a) groups (15 to amp;lt;30 mg/dL, 30 to amp;lt;50 mg/dL, and amp;gt;= 50 mg/dL, vs amp;lt;15 mg/dL), before pooling estimates using multivariate random-effects meta-analysis. Findings Analyses included data for 29 069 patients with repeat lipoprotein(a) measurements (mean age 62 years [SD 8]; 8064 [28%] women; 5751 events during 95 576 person-years at risk). Initiation of statin therapy reduced LDL cholesterol (mean change -39% [95% CI -43 to -35]) without a significant change in lipoprotein(a). Associations of baseline and on-statin treatment lipoprotein(a) with cardiovascular disease risk were approximately linear, with increased risk at lipoprotein(a) values of 30 mg/dL or greater for baseline lipoprotein(a) and 50 mg/dL or greater for on-statin lipoprotein(a). For baseline lipoprotein(a), HRs adjusted for age and sex (vs amp;lt;15 mg/dL) were 1.04 (95% CI 0.91-1.18) for 15 mg/dL to less than 30 mg/dL, 1.11 (1.00-1.22) for 30 mg/dL to less than 50 mg/dL, and 1.31 (1.08-1.58) for 50 mg/dL or higher; respective HRs for on-statin lipoprotein(a) were 0.94 (0.81-1.10), 1.06 (0. 94-1.21), and 1.43 (1.15-1.76). HRs were almost identical after further adjustment for previous cardiovascular disease, diabetes, smoking, systolic blood pressure, LDL cholesterol, and HDL cholesterol. The association of on-statin lipoprotein(a) with cardiovascular disease risk was stronger than for on-placebo lipoprotein(a) (interaction p=0.010) and was more pronounced at younger ages (interaction p=0.008) without effect-modification by any other patient-level or study-level characteristics. Interpretation In this individual-patient data meta-analysis of statin-treated patients, elevated baseline and on-statin lipoprotein(a) showed an independent approximately linear relation with cardiovascular disease risk. This study provides a rationale for testing the lipoprotein(a) lowering hypothesis in cardiovascular disease outcomes trials. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

  • 3.
    Rosenson, Robert S
    et al.
    Icahn School of Medicine at Mount Sinai, USA.
    Larrey, Dominique
    Hepato-Gastroentérologie, CHU de Montpellier, Hôpital Saint-Eloi, Montpellier, France.
    Waters, David D
    Division of Cardiology, San Francisco General Hospital, San Francisco, CA, USA.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Heart Center, Stockholm, Sweden.
    Comments: Praluent (Alirocumab)-Induced Renal Injury2018Ingår i: Journal of Pharmacy Practice, ISSN 0897-1900, E-ISSN 1531-1937, Vol. 31, nr 2, s. 138-139Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 4.
    Pitts, Reynaria
    et al.
    VA Medical Centre, CO USA; University of Colorado, CO USA.
    Gunzburger, Elise
    University of Colorado, CO USA.
    Ballantyne, Christie M.
    Baylor Coll Med, TX 77030 USA.
    Barter, Philip J.
    University of New South Wales, Australia.
    Kallend, David
    Medicines Co, Switzerland.
    Leiter, Lawrence A.
    University of Toronto, Canada; University of Toronto, Canada.
    Leitersdorf, Eran
    Hadassah Hebrew University, Israel.
    Nicholls, Stephen J.
    University of Adelaide, Australia; University of Adelaide, Australia.
    Shah, Prediman K.
    Cedars Sinai Heart Institute, CA USA.
    Tardif, Jean-Claude
    University of Montreal, Canada.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    McMurray, John J. V.
    University of Glasgow, Scotland.
    Kittelson, John
    University of Colorado, CO USA.
    Schwartz, Gregory G.
    VA Medical Centre, CO USA; University of Colorado, CO USA.
    Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure2017Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, nr 1, artikel-id e004119Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background- Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk. Methods and Results- To address this question, we examined data from the dal-OUTCOMES trial that compared the cholesteryl ester transfer protein inhibitor dalcetrapib with placebo, beginning 4 to 12 weeks after an index acute coronary syndrome. Patients with New York Heart Association class II (with LVEF amp;lt; 40%), III, or IV HF were excluded. Aldosterone was measured at randomization in 4073 patients. The primary outcome was a composite of coronary heart disease death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, or resuscitated cardiac arrest. Hospitalization for HF was a secondary endpoint. Over a median follow-up of 37 months, the primary outcome occurred in 366 patients (9.0%), and hospitalization for HF occurred in 72 patients (1.8%). There was no association between aldosterone and either the time to first occurrence of a primary outcome (hazard ratio for doubling of aldosterone 0.92, 95% confidence interval 0.78-1.09, P=0.34) or hospitalization for HF (hazard ratio 1.38, 95% CI 0.96-1.99, P=0.08) in Cox regression models adjusted for covariates. Conclusions- In patients with recent acute coronary syndrome but without advanced HF, aldosterone does not predict major cardiovascular events.

  • 5.
    Olsson, Anders
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Angelin, B.
    Karolinska Institute, Sweden; Karolinska University Hospital Huddinge, Sweden.
    Assmann, G.
    University of Munster, Germany.
    Binder, C. J.
    Medical University of Vienna, Austria; Austrian Academic Science, Austria.
    Bjoerkhem, I.
    Karolinska University Hospital Huddinge, Sweden; Karolinska Institute, Sweden.
    Cedazo-Minguez, A.
    Karolinska Institute Huddinge, Sweden.
    Cohen, J.
    UTSouthwesternMedical Centre, TX USA.
    von Eckardstein, A.
    University of Zurich, Switzerland.
    Farinaro, E.
    University of Naples Federico II, Italy.
    Mueller-Wieland, D.
    University of Cologne, Germany.
    Parhofer, K. G.
    Ludwig Maximilians University of Munchen, Germany.
    Parini, P.
    Karolinska University Hospital Huddinge, Sweden; Karolinska Institute, Sweden.
    Rosenson, R. S.
    Mt Sinai Hospital, NY 10029 USA.
    Starup-Linde, J.
    University of Aarhus, Denmark.
    Tikkanen, M. J.
    University of Helsinki, Finland.
    Yvan-Charvet, L.
    University of Nice Sophia Antipolis, France.
    Can LDL cholesterol be too low? Possible risks of extremely low levels2017Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, nr 6, s. 534-553Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans. In this review, we summarize information from studies of human cellular and organ physiology, phenotypic characterization of rare genetic diseases of lipid metabolism, and experience from clinical trials. Specifically, we emphasize the importance of the robustness of the regulatory systems that maintain balanced fluxes and levels of cholesterol at both cellular and organismal levels. Even at extremely low LDL-C levels, critical capacities of steroid hormone and bile acid production are preserved, and the presence of a cholesterol blood-brain barrier protects cells in the central nervous system. Apparent relationships sometimes reported between less pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment, whilst further evaluation of more potent LDL-lowering treatments such as PCSK9 inhibitors is needed. Experience from the recently reported and ongoing large event-driven trials are of great interest, and further evaluation including careful analysis of cognitive functions will be important. This is an article from the symposium: Risks and benefits of Extremely Low LDL Cholesterol.

  • 6.
    Schwartz, Gregory G.
    et al.
    VA Medical Centre, DC USA; University of Colorado, CO 80309 USA.
    Fayyad, Rana
    Pfizer Inc, NY USA.
    Szarek, Michael
    Suny Downstate Medical Centre, NY 11203 USA.
    DeMicco, David
    Pfizer Inc, NY USA.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Early, intensive statin treatment reduces hard cardiovascular outcomes after acute coronary syndrome2017Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, nr 12, s. 1294-1296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Early, intensive statin treatment is the standard of care after acute coronary syndrome (ACS). However, the benefit of this approach to prevent major adverse cardiovascular events has been demonstrated in only one randomised, placebo controlled trial. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial demonstrated that atorvastatin 80 mg daily, compared with placebo, reduced time to first occurrence of death, non-fatal myocardial infarction, resuscitated cardiac arrest, or hospitalisation for unstable angina (stroke not included) during the 16 week period following ACS. However, there were no significant effects on individual components of the composite endpoint except unstable angina. This led some to question whether early, intensive statin treatment reduces hard events after ACS. Aim: The burden of coronary heart disease after ACS, and therefore the efficacy of its treatment, depends not only on the occurrence of one ischaemic event, but rather on cumulative events experienced by patients. Accordingly, we conducted a post-hoc analysis of the MIRACL trial to examine the effect of atorvastatin on first as well as recurrent (i.e. total) hard cardiovascular events after ACS (death, myocardial infarction, stroke, and resuscitated cardiac arrest). Methods and Results: In the 3086 patients who comprised the MIRACL trial, atorvastatin 80 mg did not reduce time to first hard event compared with placebo (hazard ratio 0.89, 95% confidence interval 0.72-1.10, P = 0.27). However, atorvastatin significantly reduced total hard events (hazard ratio 0.80, 95% confidence interval 0.66-0.97, P = 0.03). To prevent one hard event during the 16 weeks following ACS, only 11 patient-years of treatment with atorvastatin were required. Conclusion: Early, intensive treatment with atorvastatin is an efficient intervention to reduce hard cardiovascular events after ACS.

  • 7.
    Tardif, Jean-Claude
    et al.
    Montreal Heart Institute, Canada; University of Montreal, Canada.
    Rhainds, David
    Montreal Heart Institute, Canada.
    Brodeur, Mathieu
    Montreal Heart Institute, Canada.
    Feroz Zada, Yassamin
    University of Montreal, Canada.
    Fouodjio, Rene
    University of Montreal, Canada.
    Provost, Sylvie
    University of Montreal, Canada.
    Boule, Marie
    Montreal Heart Institute, Canada.
    Alem, Sonia
    Montreal Heart Institute, Canada.
    Gregoire, Jean C.
    Montreal Heart Institute, Canada; University of Montreal, Canada.
    LAllier, Philippe L.
    Montreal Heart Institute, Canada; University of Montreal, Canada.
    Ibrahim, Reda
    Montreal Heart Institute, Canada; University of Montreal, Canada.
    Guertin, Marie-Claude
    Montreal Health Innovat Coordinating Centre, Canada.
    Mongrain, Ian
    University of Montreal, Canada.
    Olsson, Anders
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Schwartz, Gregory G.
    Vet Affairs Medical Centre, CO USA; University of Colorado, CO USA.
    Rheaume, Eric
    Montreal Heart Institute, Canada; University of Montreal, Canada.
    Dube, Marie-Pierre
    Montreal Heart Institute, Canada; University of Montreal, Canada; University of Montreal, Canada.
    Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation Concordance With Clinical Outcomes2016Ingår i: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 9, nr 4, s. 340-348Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-Dalcetrapib effects on cardiovascular outcomes are determined by adenylate cyclase 9 gene polymorphisms. Our aim was to determine whether these clinical end point results are also associated with changes in reverse cholesterol transport and inflammation. Methods and Results-Participants of the dal-OUTCOMES and dal-PLAQUE-2 trials were randomly assigned to receive dalcetrapib or placebo in addition to standard care. High-sensitivity C-reactive protein was measured at baseline and at end of study in 5243 patients from dal-OUTCOMES also genotyped for the rs1967309 polymorphism in adenylate cyclase 9. Cholesterol efflux capacity of high-density lipoproteins from J774 macrophages after cAMP stimulation was determined at baseline and 12 months in 171 genotyped patients from dal-PLAQUE-2. Treatment with dalcetrapib resulted in placebo-adjusted geometric mean percent increases in high-sensitivity C-reactive protein from baseline to end of trial of 18.1% (P=0.0009) and 18.7% (P=0.00001) in participants with the GG and AG genotypes, respectively, but the change was -1.0% (P=0.89) in those with the protective AA genotype. There was an interaction between the treatment arm and the genotype groups (P=0.02). Although the mean change in cholesterol efflux was similar among study arms in patients with GG genotype (mean: 7.8% and 7.4%), increases were 22.3% and 3.5% with dalcetrapib and placebo for those with AA genotype (P=0.005). There was a significant genetic effect for change in efflux for dalcetrapib (P=0.02), but not with placebo. Conclusions-Genotype-dependent effects on C-reactive protein and cholesterol efflux are supportive of dalcetrapib benefits on atherosclerotic cardiovascular outcomes in patients with the AA genotype at polymorphism rs1967309.

  • 8.
    Müller-Wieland, Dirk
    et al.
    Asklepios Clinic St Georg, Hamburg, Germany .
    Assmann, Gerd
    Assmann-Foundation for Prevention, Münster, Germany.
    Carmena, Rafael
    University, Valencia, Spain .
    Davignon, Jean
    Faculty of Medicine at the Université de Montréal, Canada.
    von Eckardstein, Arnold
    University Hospital of Zurich, Switzerland.
    Farinaro, Eduardo
    Medical School University of Naples Federico II, Italy.
    Greten, Heiner
    Asklepios Clinic St Georg, Hamburg, Germany.
    Olsson, Anders G
    Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Stockholm Heart Centre, Sweden.
    Riesen, Walter F
    Institute for Laboratory Medicine, St Gallen, Switzerland.
    Shlyakhto, Evgenyi
    Russian Federation Agency of Health and Social Development, Saint Petersburg, Russia.
    Treat-to-target versus dose-adapted statin treatment of cholesterol to reduce cardiovascular risk.2016Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, nr 3, s. 275-281Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Clinical guidelines should be based on the best available evidence and are of great importance for patient care and disease prevention. In this respect, the 2013 American College of Cardiology/American Heart Association report is highly appreciated and well-recognized. The report included critical questions concerning hypercholesterolaemia, but its translation into a clinical guideline initiated intense debate worldwide because of the recommendation to switch from a treat-to-target approach for low-density-lipoprotein-cholesterol to a statin dose-based strategy.

  • 9.
    Schwartz, Gregory G.
    et al.
    Denver VA Medical Centre, CO 80220 USA; University of Colorado, CO 80202 USA.
    Abt, Markus
    F Hoffmann La Roche, Switzerland.
    Bao, Weihang
    Pfizer Inc, NY USA.
    DeMicco, David
    Pfizer Inc, NY USA.
    Kallend, David
    F Hoffmann La Roche, Switzerland.
    Miller, Michael
    University of Maryland, MD 21201 USA.
    Mundl, Hardi
    F Hoffmann La Roche, Switzerland.
    Olsson, Anders
    Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Stockholm Heart Centre, Sweden.
    Fasting Triglycerides Predict Recurrent Ischemic Events in Patients With Acute Coronary Syndrome Treated With Statins2015Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 65, nr 21, s. 2267-2275Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Most patients with acute coronary syndrome (ACS) are treated with statins, which reduce atherogenic triglyceride-rich lipoproteins. It is uncertain whether triglycerides predict risk after ACS on a background of statin treatment. OBJECTIVES This study examined the relationship of fasting triglyceride levels to outcomes after ACS in patients treated with statins. METHODS Long-term and short-term relationships of triglycerides to risk after ACS were examined in the dal-OUTCOMES trial and atorvastatin arm of the MIRACL (Myocardial Ischemia Reduction with Acute Cholesterol Lowering) trial, respectively. Analysis of dal-OUTCOMES included 15,817 patients (97% statin-treated) randomly assigned 4 to 12 weeks after ACS to treatment with dalcetrapib (a cholesteryl ester transfer protein inhibitor) or placebo and followed for a median 31 months. Analysis of MIRACL included 1,501 patients treated with atorvastatin 80 mg daily beginning 1 to 4 days after ACS and followed for 16 weeks. Fasting triglycerides at initial random assignment were related to risk of coronary heart disease death, nonfatal myocardial infarction, stroke, and unstable angina in models adjusted for age, sex, hypertension, smoking, diabetes, high-density lipoprotein cholesterol, and body mass index. RESULTS Fasting triglyceride levels were associated with both long-term and short-term risk after ACS. In dalOUTCOMES, long-term risk increased across quintiles of baseline triglycerides (p less than 0.001). The hazard ratio in the highest/lowest quintile (greater than 175/less than= 80 mg/dl) was 1.50 (95% confidence interval: 1.05 to 2.15). There was no interaction of triglycerides and treatment assignment on the primary outcome. In the atorvastatin group of MIRACL, short-term risk increased across tertiles of baseline triglycerides (p = 0.03), with a hazard ratio of 1.51 (95% confidence interval: 1.05 to 2.15) in highest/lowest tertiles (greater than195/less than= 135 mg/dl). The relationship of triglycerides to risk was independent of lowdensity lipoprotein cholesterol in both studies. CONCLUSIONS Among patients with ACS treated effectively with statins, fasting triglycerides predict long-term and short-term cardiovascular risk. Triglyceride-rich lipoproteins may be an important additional target for therapy. (C) 2015 by the American College of Cardiology Foundation.

  • 10.
    Raal, Frederick J.
    et al.
    University of Witwatersrand, South Africa.
    Stein, Evan A.
    Metab and Atherosclerosis Research Centre, OH USA.
    Dufour, Robert
    Institute Rech Clin Montreal, Canada.
    Turner, Traci
    Metab and Atherosclerosis Research Centre, OH USA.
    Civeira, Fernando
    University Hospital Miguel Servet, Spain.
    Burgess, Lesley
    Tygerberg Hospital, South Africa.
    Langslet, Gisle
    Oslo University Hospital, Norway.
    Scott, Russell
    University of Otago, New Zealand; Amgen Inc, CA 91320 USA.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Stockholm Heart Centre, Sweden.
    Sullivan, David
    Royal Prince Alfred Hospital, Australia.
    Kees Hovingh, G.
    University of Amsterdam, Netherlands.
    Cariou, Bertrand
    Nantes University Hospital, France.
    Gouni-Berthold, Ioanna
    University of Cologne, Germany.
    Somaratne, Ransi
    Amgen Inc, CA 91320 USA.
    Bridges, Ian
    Amgen Ltd, MA USA.
    Scott, Rob
    University of Otago, New Zealand; Amgen Inc, CA 91320 USA.
    Wasserman, Scott M.
    Amgen Inc, CA 91320 USA.
    Gaudet, Daniel
    University of Montreal, Canada.
    PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial2015Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, nr 9965, s. 331-340Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Heterozygous familial hypercholesterolaemia is characterised by low cellular uptake of LDL cholesterol, increased plasma LDL cholesterol concentrations, and premature cardiovascular disease. Despite intensive statin therapy, with or without ezetimibe, many patients are unable to achieve recommended target levels of LDL cholesterol. We investigated the effect of PCSK9 inhibition with evolocumab (AMG 145) on LDL cholesterol in patients with this disorder. Methods This multicentre, randomised, double-blind, placebo-controlled trial was undertaken at 39 sites (most of which were specialised lipid clinics, mainly attached to academic institutions) in Australia, Asia, Europe, New Zealand, North America, and South Africa between Feb 7 and Dec 19,2013.331 eligible patients (18-80 years of age), who met clinical criteria for heterozygous familial hypercholesterolaemia and were on stable lipid-lowering therapy for at least 4 weeks, with a fasting LDL cholesterol concentration of 2.6 mmol/L or higher, were randomly allocated in a 2:2:1:1 ratio to receive subcutaneous evolocumab 140 mg every 2 weeks, evolocumab 420 mg monthly, or subcutaneous placebo every 2 weeks or monthly for 12 weeks. Randomisation was computer generated by the study sponsor, implemented by a computerised voice interactive system, and stratified by LDL cholesterol concentration at screening (higher or lower than 4.1 mmol/L) and by baseline ezetimibe use (yes/no). Patients, study personnel, investigators, and Amgen study staff were masked to treatment assignments within dosing frequency groups. The coprimary endpoints were percentage change from baseline in LDL cholesterol at week 12 and at the mean of weeks 10 and 12, analysed by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01763918. Findings Of 415 screened patients, 331 were eligible and were randomly assigned to the four treatment groups: evolocumab 140 mg every 2 weeks (n=111), evolocumab 420 mg monthly (n=110), placebo every 2 weeks (n=55), or placebo monthly (n=55). 329 patients received at least one dose of study drug. Compared with placebo, evolocumab at both dosing schedules led to a significant reduction in mean LDL cholesterol at week 12 (every-2-weeks dose: 59.2% reduction [95% CI 53.4-65.1], monthly dose: 61.3% reduction [53.6-69.0]; both pless than0.0001) and at the mean of weeks 10 and 12 (60.2% reduction [95% CI 54.5-65.8] and 65.6% reduction [59.8-71.3]; both pless than0.0001). Evolocumab was well tolerated, with rates of adverse events similar to placebo. The most common adverse events occurring more frequently in the evolocumab-treated patients than in the placebo groups were nasopharyngitis (in 19 patients [9%] vs five [5%] in the placebo group) and muscle-related adverse events (ten patients [5%] vs 1 [1%]). Interpretation In patients with heterozygous familial hypercholesterolaemia, evolocumab administered either 140 mg every 2 weeks or 420 mg monthly was well tolerated and yielded similar and rapid 60% reductions in LDL cholesterol compared with placebo.

  • 11.
    Angelin, Bo
    et al.
    Karolinska University, Sweden; Karolinska University, Sweden.
    Kristensen, Jens D.
    Karo Bio AB, Sweden.
    Eriksson, Mats
    Karolinska University, Sweden; Karolinska University, Sweden.
    Carlsson, Bo
    Karo Bio AB, Sweden.
    Klein, Irwin
    NYU, NY USA.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken. Stockholm Heart Centre, Sweden.
    Chester Ridgway, E.
    University of Colorado, CO USA.
    Ladenson, Paul W.
    Johns Hopkins University, MD 21205 USA.
    Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome2015Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, nr 3, s. 331-342Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundLiver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia. MethodsWe performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200gday(-1) eprotirome or placebo for 12weeks. The primary end-point was change in serum LDL cholesterol; secondary end-points included changes in other lipid parameters and safety measures. ResultsEprotirome treatment at 100 and 200g daily reduced serum LDL cholesterol levels by 235% and 31 +/- 4%, respectively, compared with 2 +/- 6% for placebo (Pless than0.0001). Similar reductions were seen in non-HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A-I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low-grade increases in liver enzymes were evident in most patients. ConclusionIn hypercholesterolaemic patients, the liver-selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra-hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.

  • 12.
    Sjouke, Barbara
    et al.
    Academic Medical Centre, Netherlands .
    Langslet, Gisle
    Oslo University Hospital, Norway .
    Ceska, Richard
    Charles University of Prague, Czech Republic Charles University of Prague, Czech Republic .
    Nicholls, Stephen J.
    Cleveland Clin, OH 44106 USA University of Adelaide, Australia University of Adelaide, Australia .
    Nissen, Steven E.
    Cleveland Clin, OH 44106 USA .
    Ohlander, Maria
    Karolinska Institute, Sweden .
    Ladenson, Paul W.
    Johns Hopkins Medical Institute, MD 21205 USA .
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Hovingh, G. Kees
    Academic Medical Centre, Netherlands .
    Kastelein, John J. P.
    Academic Medical Centre, Netherlands .
    Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a randomised, double-blind, placebo-controlled phase 3 study2014Ingår i: LANCET DIABETES and ENDOCRINOLOGY, ISSN 2213-8587, Vol. 2, nr 6, s. 455-463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Eprotirome is a liver-selective thyroid hormone receptor agonist that has been shown to lower plasma LDL cholesterol concentrations in previous phase 1 and 2 studies of patients with dyslipidaemia. We aimed to assess the long-term safety and efficacy of 50 mu g and 100 mu g eprotirome in patients with familial hypercholesterolaemia. Methods For this randomised, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial, we enrolled patients between Oct 3, 2011, and Feb 14, 2012, at 53 sites in 11 countries in Europe, Africa, and south Asia. Patients were eligible for enrolment if they were aged 18 years or older, diagnosed with heterozygous familial hypercholesterolaemia, and had not reached target LDL cholesterol concentrations after at least 8 weeks of statin therapy with or without ezetimibe. We used a computer-generated randomisation sequence to allocate patients to one of three groups: 50 mu g eprotirome, 100 mu g eprotirome, or placebo. This trial was planned for 52-76 weeks, with primary efficacy analysis at 12 weeks, but it was prematurely terminated when another study found that eprotirome causes cartilage damage in dogs. Although it was impossible to meet the predefined study outcomes, we analysed changes in the concentrations of LDL cholesterol and other lipids, liver parameters, thyroid hormone concentrations, and adverse effects of treatment with eprotirome versus placebo at 6 weeks of treatment. Analysis was done in all patients who received 6 weeks of treatment. This study is registered with ClinicalTrials.gov, number NCT01410383. Findings We enrolled 236 patients, randomly allocating 80 to receive placebo, 79 to receive 50 mu g eprotirome, and 77 to receive 100 mu g eprotirome. 69 patients reached the 6 week timepoint (23 given placebo, 24 given 50 mu g eprotirome, and 22 given 100 mu g eprotirome). Mean LDL cholesterol concentrations increased by 9% (95% CI -2 to 20) in the placebo group, decreased by 12% (-28 to 4%; p=0.0677 vs placebo) in the 50 mu g eprotirome group, and decreased by 22% (-32 to -13%; p=0.0045 vs placebo) in the 100 mu g eprotirome group. We noted statistically significant increases between both eprotirome groups and placebo in aspartate aminotransferase (AST; pless than0.0001), alanine aminotransferase (ALT; pless than0.0001), conjugated bilirubin (p=0.0006), and gamma-glutamyltranspeptidase (pless than0.0001). Four patients had to discontinue or interrupt study treatment before trial termination due to AST increases between the upper limit of normal (ULN) and six times ULN, and ALT concentrations between three and seven times ULN. Although we detected no changes in serum concentrations of thyroid-stimulating hormone or free tri-iodothyronine, free tetra-iodothyronine decreased by 19% (23 to 16) in the 50 mu g eprotirome group and 27% (30 to 23) in the 100 mu g eprotirome group (pless than0.0001 vs placebo for both groups). Interpretation Our findings show that eprotirome can lower LDL cholesterol concentrations in patients with familial hypercholesterolaemia when added to conventional statin treatment with or without ezetimibe, but that it has the potential to induce liver injury. These findings, along with findings of cartilage damage in dogs, raise serious doubts about selective thyroid hormone mimetics as a therapeutic approach to lower LDL cholesterol concentrations.

  • 13.
    Olsson, Anders G
    Linköpings universitet, Institutionen för medicin och hälsa. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    [Guidelines for cholesterol treatment--the obstacle remains in Stockholm].2014Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 20, s. 885-Artikel i tidskrift (Övrigt vetenskapligt)
  • 14.
    Tikkanen, Matti J.
    et al.
    University of Helsinki, Finland .
    Fayyad, Rana
    Pfizer Inc, NY USA .
    Faergeman, Ole
    Arhus University Hospital, Denmark .
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Wun, Chuan-Chuan
    Pfizer Inc, NY USA .
    Laskey, Rachel
    Pfizer Inc, NY USA .
    Kastelein, John J.
    University of Amsterdam, Netherlands .
    Holme, Ingar
    Oslo University Hospital, Norway .
    Pedersen, Terje R.
    University of Oslo, Norway .
    Effect of intensive lipid lowering with atorvastatin on cardiovascular outcomes in coronary heart disease patients with mild-to-moderate baseline elevations in alanine aminotransferase levels2013Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, nr 4, s. 3846-3852Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Statins may reduce cardiovascular (CV) morbidity in patients with mild-to-moderate elevations in liver enzyme levels. This post-hoc analysis of the IDEAL study compared intensive versus moderate statin therapy for the prevention of CV events in coronary heart disease patients with normal and elevated baseline levels of serum alanine aminotransferase (ALT). less thanbrgreater than less thanbrgreater thanMethods: Cox regression analysis was used to investigate the effect of atorvastatin 80 mg/day versus simvastatin 20-40 mg/day on the risk of IDEAL study end points in patients with normal baseline ALT (defined as ALT andlt; ULN [upper limit of normal]) versus elevated baseline ALT (ALT andgt;= ULN). less thanbrgreater than less thanbrgreater thanResults: Of 8863 IDEAL patients with non-missing baseline ALT values, 7782 (87.8%) had an ALT andlt; ULN and 1081 (12.2%) had an ALT andgt;= ULN. In patients with elevated baseline ALT, major CV event rates were 11.5% for simvastatin and 6.5% for atorvastatin, indicating a significant risk reduction with intensive statin therapy (hazard ratio, 0.556; 95% confidence interval, 0.367-0.842; p = 0.0056). Significant heterogeneity of treatment effect was observed for major CV events, cerebrovascular events, and major coronary events, with a trend towards treatment difference for the other outcomes, indicating a greater benefit with atorvastatin in the elevated ALT group. less thanbrgreater than less thanbrgreater thanConclusions: The CV benefit of intensive lipid lowering with atorvastatin compared with a more moderate regimen with simvastatin was generally greater in patients with mildly-to-moderately elevated baseline ALT than patients with normal baseline ALT. Moderate elevations in liver enzyme levels should not present a barrier to prescribing statins, even at higher doses, in high-risk patients.

  • 15.
    Zamani, Payman
    et al.
    Hospital University of Penn, PA USA .
    Schwartz, Gregory G.
    University of Colorado, CO USA .
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Rifai, Nader
    Childrens Hospital, MA USA .
    Bao, Weihang
    Pfizer Pharmaceut Grp, NY USA .
    Libby, Peter
    VA Boston Healthcare Syst, MA USA .
    Ganz, Peter
    San Francisco Gen Hospital, CA USA .
    Kinlay, Scott
    VA Boston Healthcare Syst, MA USA .
    Inflammatory Biomarkers, Death, and Recurrent Nonfatal Coronary Events After an Acute Coronary Syndrome in the MIRACL Study2013Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 2, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-In acute coronary syndromes, C-reactive protein (CRP) strongly relates to subsequent death, but surprisingly not to recurrent myocardial infarction. Other biomarkers may reflect different processes related to these outcomes. We assessed 8 inflammatory and vascular biomarkers and the risk of death and recurrent nonfatal cardiovascular events in the 16 weeks after an acute coronary syndrome. less thanbrgreater than less thanbrgreater thanMethods and Results-We measured blood concentrations of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), soluble intercellular adhesion molecule (ICAM), soluble vascular cell adhesion molecule (VCAM), E-selectin, P-selectin, and tissue plasminogen activator antigen (tPA) 24 to 96 hours after presentation with acute coronary syndrome in 2925 subjects participating in a multicenter study. Biomarkers were related to the risk of death, and recurrent nonfatal acute coronary syndromes (myocardial infarction or unstable angina) over 16 weeks using Cox proportional hazard models. On univariate analyses, baseline CRP (P=0.006), SAA (P=0.012), and IL-6 (Pandlt;0.001) were related to death, but not to recurrent nonfatal acute coronary syndromes. VCAM and tPA related to the risk of death (Pandlt;0.001, P=0.021, respectively) and to nonfatal acute coronary syndromes (P=0.021, P=0.049, respectively). Adjusting for significant covariates reduced the strength of the associations; however, CRP and SAA continued to relate to death. less thanbrgreater than less thanbrgreater thanConclusions-In acute coronary syndromes, the CRP inflammatory axis relates to the risk of death and may reflect myocardial injury. VCAM and tPA may have greater specificity for processes reflecting inflammation and thrombosis in the epicardial arteries, which determine recurrent coronary events.

  • 16.
    Holmes, Michael V.
    et al.
    UCL, England .
    Simon, Tabassome
    Hop St Antoine, France .
    J Exeter, Holly
    UCL, England .
    Folkersen, Lasse
    Karolinska Institute, Sweden .
    Asselbergs, Folkert W.
    University of Medical Centre Utrecht, Netherlands .
    Guardiola, Montse
    University of Rovira and Virgili, Spain .
    Cooper, Jackie A.
    UCL, England .
    Palmen, Jutta
    UCL, England .
    Hubacek, Jaroslav A.
    Institute Clin and Expt Med, Czech Republic .
    Carruthers, Kathryn F.
    University of Edinburgh, Scotland .
    Horne, Benjamin D.
    Intermt Medical Centre, UT USA .
    Brunisholz, Kimberly D.
    Intermt Medical Centre, UT USA .
    Mega, Jessica L.
    Brigham and Womens Hospital, MA USA .
    Van Iperen, Erik P A
    Durrer Centre Cardiogenet Research, Netherlands .
    Li, Mingyao
    University of Penn School Med, PA USA .
    Leusink, Maarten
    University of Utrecht, Netherlands .
    Trompet, Stella
    Leiden University of Medical Centre, Netherlands .
    Verschuren, Jeffrey J W.
    Leiden University of Medical Centre, Netherlands .
    Kees Hovingh, G
    University of Amsterdam, Netherlands .
    Dehghan, Abbas
    Erasmus MC, Netherlands .
    Nelson, Christopher P.
    University of Leicester, England .
    Kotti, Salma
    Hop St Antoine, France .
    Danchin, Nicolas
    University of Ulm, Germany .
    Scholz, Markus
    University of Leipzig, Germany .
    Haase L., Christiane
    Copenhagen University Hospital, Denmark .
    Rothenbacher, Dietrich
    University of Ulm, Germany .
    Swerdlow, Daniel I.
    UCL, England .
    Kuchenbaecker, Karoline B.
    University of Cambridge, England .
    Staines-Urias, Eleonora
    London School Hyg and Trop Med, England .
    Goel, Anuj
    University of Oxford, England .
    van t Hooft, Ferdinand
    Karolinska Institute, Sweden .
    Gertow, Karl
    Karolinska Institute, Sweden .
    de Faire, Ulf
    Karolinska Institute, Sweden .
    Panayiotou, Andrie G.
    Cyprus Cardiovasc Educ and Research Trust, Cyprus .
    Tremoli, Elena
    University of Milan, Italy .
    Baldassarre, Damiano
    University of Milan, Italy .
    Veglia, Fabrizio
    IRCCS, Italy .
    Holdt, Lesca M.
    University of Leipzig, Germany .
    Beutner, Frank
    University of Leipzig, Germany .
    Gansevoort, Ron T.
    University of Groningen, Netherlands .
    Navis, Gerjan J.
    University of Groningen, Netherlands .
    Mateo Leach, Irene
    University of Groningen, Netherlands .
    Breitling, Lutz P.
    German Cancer Research Centre, Germany .
    Brenner, Hermann
    German Cancer Research Centre, Germany .
    Thiery, Joachim
    University of Leipzig, Germany .
    Dallmeier, Dhayana
    University of Ulm Medical Centre, Germany .
    Franco-Cereceda, Anders
    Karolinska Institute, Sweden .
    Boer, Jolanda M A.
    National Institute Public Health and Environm, Netherlands .
    Stephens, Jeffrey W.
    Swansea University, Wales .
    Hofker, Marten H.
    University of Groningen, Netherlands .
    Tedgui, Alain
    INSERM, France .
    Hofman, Albert
    Erasmus MC, Netherlands .
    Uitterlinden, Andre G.
    Erasmus MC, Netherlands .
    Adamkova, Vera
    Institute Clin and Expt Med, Czech Republic .
    Pitha, Jan
    Institute Clin and Expt Med, Czech Republic .
    Onland-Moret, Charlotte N.
    University of Medical Centre Utrecht, Netherlands .
    Cramer, Maarten J.
    University of Medical Centre Utrecht, Netherlands .
    Nathoe, Hendrik M.
    University of Medical Centre Utrecht, Netherlands .
    Spiering, Wilko
    University of Medical Centre Utrecht, Netherlands .
    Klungel, Olaf H.
    University of Utrecht, Netherlands .
    Kumari, Meena
    UCL, England .
    Whincup, Peter H.
    University of London, England .
    Morrow, David A.
    Brigham and Womens Hospital, MA USA .
    Braund, Peter S.
    University of Leicester, England .
    Hall, Alistair S.
    University of Leeds, England .
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten. Stockholm Heart Centre, Sweden .
    Doevendans, Pieter A.
    University of Medical Centre Utrecht, Netherlands .
    Trip, Mieke D.
    University of Amsterdam, Netherlands .
    Tobin, Martin D.
    University of Leicester, England .
    Hamsten, Anders
    Karolinska Institute, Sweden .
    Watkins, Hugh
    University of Oxford, England .
    Koenig, Wolfgang
    University of Ulm Medical Centre, Germany .
    Nicolaides, Andrew N.
    University of London Imperial Coll Science Technology and Med, England .
    Teupser, Daniel
    University of Leipzig, Germany .
    Day, Ian N M
    Hop St Antoine, France .
    F Carlquist, John
    Intermt Medical Centre, UT USA .
    Gaunt, Tom R.
    University of Bristol, England .
    Ford, Ian
    University of Glasgow, Scotland .
    Sattar, Naveed
    University of Glasgow, Scotland .
    Tsimikas, Sotirios
    University of Calif San Diego, CA USA .
    Schwartz, Gregory G.
    VA Medical Centre, CO USA .
    Lawlor, Debbie A.
    University of Bristol, England .
    Morris, Richard W.
    UCL, England .
    Sandhu, Manjinder S.
    VA Medical Centre, CO USA .
    Poledne, Rudolf
    Institute Clin and Expt Med, Czech Republic .
    Maitland-van der Zee, Anke H.
    University of Utrecht, Netherlands .
    Khaw, Kay-Tee
    University of Cambridge, England .
    Keating, Brendan J.
    Childrens Hospital Philadelphia, PA USA .
    van der Harst, Pim
    University of Groningen, Netherlands .
    Price, Jackie F.
    University of Edinburgh, Scotland .
    Mehta, Shamir R.
    McMaster University, Canada .
    Yusuf, Salim
    McMaster University, Canada .
    Witteman, Jaqueline C M
    Erasmus MC, Netherlands .
    Franco, Oscar H.
    Erasmus MC, Netherlands .
    Jukema, Wouter J.
    Durrer Centre Cardiogenet Research, Netherlands .
    de Knijff, Peter
    Leiden University of Medical Centre, Netherlands .
    Tybjaerg-Hansen, Anne
    Copenhagen University Hospital, Denmark .
    Rader, Daniel J.
    Penn Heart and Vasc Centre, PA USA .
    Farrall, Martin
    University of Oxford, England .
    Samani, Nilesh J.
    University of Leicester, England .
    Kivimaki, Mika
    UCL, England .
    Fox, Keith A A.
    University of Edinburgh, Scotland .
    Humphries, Steve E.
    UCL, England .
    Anderson, Jeffrey L.
    Intermt Medical Centre, UT USA .
    Boekholdt, Matthijs S.
    University of Amsterdam, Netherlands .
    Palmer, Tom M.
    University of Warwick, England .
    Eriksson, Per
    Karolinska Institute, Sweden .
    Pare, Guillaume
    McMaster University, Canada .
    Hingorani, Aroon D.
    UCL, England .
    Sabatine, Marc S.
    Brigham and Womens Hospital, MA USA .
    Mallat, Ziad
    INSERM, France .
    Casas, Juan P.
    UCL, England .
    Talmud, Philippa J.
    UCL, England .
    Secretory Phospholipase A(2)-IIA and Cardiovascular Disease2013Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 62, nr 21, s. 1966-1976Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.

  • 17.
    Gandhi, Sanya K.
    et al.
    AstraZeneca LP, Wilmington, DE, USA.
    Jensen, Marie M.
    AstraZeneca, Lund, Sweden.
    Fox, Kathleen M.
    Strategic HealthCare Solution, Monkton, MD, USA.
    Smolen, Lee
    Medical Decision Modeling Inc, Indianapolis, IN, USA.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Paulsson, Thomas
    AstraZeneca, Södertälje, Sweden.
    Cost-effectiveness of resuvastatin in comparison with generic atorvastatin and simvastatin in a Swedish population at high risk of cardiovascular events2012Ingår i: ClinicoEconomics and Outcomes Research, ISSN 1178-6981, Vol. 4, s. 1-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To assess the long-term cost-effectiveness of rosuvastatin therapy compared with generic simvastatin and generic atorvastatin in reducing the incidence of cardiovascular events and mortality in a Swedish population with Framingham risk ≥20%.

    Methods: A probabilistic Monte Carlo simulation model based on data from JUPITER (the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) was used to estimate the long-term cost-effectiveness of rosuvastatin 20 mg daily versus simvastatin or atorvastatin 40 mg for the prevention of cardiovascular death and morbidity. The three-stage model included cardiovascular event prevention simulating the 4 years of JUPITER, initial prevention beyond the trial, and subsequent cardiovascular event prevention. A Swedish health care payer perspective (direct costs only) was modeled for a lifetime horizon, with 2008/2009 as the costing period. Univariate and probabilistic sensitivity analyses were performed.

    Results: The incremental cost per quality-adjusted life-year (QALY) gained with rosuvastatin 20 mg over simvastatin or atorvastatin 40 mg ranged from SEK88,113 (rosuvastatin 20 mg versus simvastatin 40 mg; Framingham risk ≥30%; net avoidance of 34 events/1000 patients) to SEK497,542 (versus atorvastatin 40 mg: Framingham risk ≥20%; net avoidance of 11 events/1000 patients) over a lifetime horizon. Probabilistic sensitivity analyses indicated that at a willingness-to-pay threshold of SEK500,000/QALY, rosuvastatin 20 mg would be cost-effective for approximately 75%–85% of simulations relative to atorvastatin or simvastatin 40 mg. Sensitivity analyses indicated the findings to be robust.

    Conclusion: Rosuvastatin 20 mg is cost-effective over a lifetime horizon compared with generic simvastatin or atorvastatin 40 mg in patients at high cardiovascular risk in Sweden.

  • 18.
    Ohsfeldt, Robert L.
    et al.
    Texas A&M Health Science Center, College Station, TX, USA.
    Olsson, Anders G
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Jensen, Marie M.
    AstraZeneca, Lund, Sweden.
    Gandhi, Sanjay K.
    AstraZeneca, LP, Wilmington, DE, USA.
    Paulsson, Thomas
    AstraZeneca, Södertälje, Sweden.
    Cost-effectiveness of rosuvastatin 20 mg for the prevention of cardiovascular morbidity and mortality: a Swedish economic evaluation of the Jupiter trial2012Ingår i: Journal of Medical Economics, ISSN 1369-6998, E-ISSN 1941-837X, Vol. 15, nr 1, s. 125-133Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    This study estimated the long-term health outcomes, healthcare costs, and cost-effectiveness of rosuvastatin 20 mg therapy in primary prevention of major cardiovascular disease (CVD) in a Swedish population.

    METHODS:

    Based on data from the JUPITER trial, long-term CVD outcomes with rosuvastatin vs no active treatment were estimated for patients with an elevated baseline CVD risk (Framingham CVD score >20%, sub-population of JUPITER population) and for a population similar to the total JUPITER population. Using a decision-analytic model, trial CVD event rates were combined with epidemiological and cost data specific for Sweden. First and subsequent CVD events and death were estimated over a lifetime perspective. The observed relative risk reduction was extrapolated beyond the trial duration. Incremental effectiveness was measured as life-years gained (LYG) and quality-adjusted life-years (QALYs) gained.

    RESULTS:

    Treating 100,000 patients with rosuvastatin 20 mg was estimated to avoid 14,692 CVD events over the lifetime (8021 non-fatal MIs, 3228 non-fatal strokes, and 4924 CVD deaths) compared to placebo. This translated into an estimated gain of 42,122 QALYs and 36,865 total life years (LYG). Rosuvastatin was both more effective and less costly over a lifetime perspective, and rosuvastatin is subsequently a dominant alternative compared to no treatment in the assessed population. Using the overall JUPITER population, rosuvastatin was dominant for the lifetime horizon. In the sensitivity analysis, rosuvastatin was the dominant treatment strategy over a 20-year time horizon, and cost-effective with an incremental cost-effectiveness ratio (cost per QALY) of SEK 1783 over a 10-year time horizon.

    LIMITATIONS:

    Some model inputs were derived from literature or other data sources, but uncertainty was controlled by sensitivity analyses.

    CONCLUSIONS:

    Results indicate that rosuvastatin 20 mg treatment is a cost-effective option vs no-treatment in patients with Framingham CVD risk >20% in Sweden and might even be cost saving if taking a long-term perspective.

  • 19.
    Sullivan, David
    et al.
    Royal Prince Alfred Hospital, Australia .
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US. Stockholm Heart Center, Stockholm, Sweden.
    Scott, Rob
    Amgen Inc, CA USA .
    Kim, Jae B
    Amgen Inc, CA USA .
    Xue, Allen
    Amgen Inc, CA USA .
    Gebski, Val
    University of Sydney, Australia .
    Wasserman, Scott M
    Amgen Inc, CA USA .
    Stein, Evan A
    Metab and Atherosclerosis Research Centre, OH 45227 USA .
    Effect of a Monoclonal Antibody to PCSK9 on Low-Density Lipoprotein Cholesterol Levels in Statin-Intolerant Patients The GAUSS Randomized Trial2012Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 308, nr 23, s. 2497-2506Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context An estimated 10% to 20% of patients cannot tolerate statins or adequate doses to achieve treatment goals. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, promoting their degradation and increasing LDL cholesterol levels. In phase 1 studies, a human monoclonal antibody to PCSK9, AMG145, was well tolerated and reduced LDL cholesterol levels. less thanbrgreater than less thanbrgreater thanObjective To assess the efficacy and tolerability of AMG145 in patients with statin intolerance due to muscle-related side effects. less thanbrgreater than less thanbrgreater thanDesign, Setting, and Patients A 12-week, randomized, double-blind, placebo- and ezetimibe-controlled, dose-ranging study conducted between July 2011 and May 2012 in statin-intolerant adult patients at 33 international sites. less thanbrgreater than less thanbrgreater thanIntervention Patients were randomized equally to 1 of 5 groups: AMG145 alone at doses of 280 mg, 350 mg, or 420 mg; AMG145 at 420 mg plus 10 mg of ezetimibe; or 10 mg of ezetimibe plus placebo. AMG145 or placebo was administered subcutaneously every 4 weeks. less thanbrgreater than less thanbrgreater thanMain Outcome Measures The primary end point was percentage change from baseline to week 12 in ultracentrifugation-measured LDL cholesterol. Other end points included measures of safety and tolerability of different doses of AMG145 and AMG145 plus ezetimibe. less thanbrgreater than less thanbrgreater thanResults Of 236 patients screened, 160 were randomized (mean age, 62 years; 64% female; mean baseline LDL cholesterol, 193 mg/dL); all patients had intolerance to 1 or more statins because of muscle-related events. At week 12, mean changes in LDL cholesterol levels were -67 mg/dL (-41%; 95% CI, -49% to -33%) for the AMG145, 280-mg, group; -70 mg/dL (-43%; 95% CI, -51% to -35%) for the 350-mg group; -91 mg/dL (-51%; 95% CI, -59% to -43%) for the 420-mg group; and -110 mg/dL (-63%; 95% CI, -71% to -55%) for the 420-mg/ezetimibe group compared with -14 mg/dL (-15%; 95% CI, -23% to -7.0%) for the placebo/ezetimibe group (Pandlt;.001). Four serious adverse events were reported with AMG145 (coronary artery disease, acute pancreatitis, hip fracture, syncope). Myalgia was the most common treatment-emergent adverse event during the study, occurring in 5 patients (15.6%) in the 280-mg group (n=32); 1 patient (3.2%) in the 350-mg group (n=31), 1 patient (3.1%) in the 420-mg group (n=32), 6 patients (20.0%) receiving 420-mg AMG145/ezetimibe, and 1 patient (3.1%) receiving placebo/ezetimibe. less thanbrgreater than less thanbrgreater thanConclusion In this phase 2 study in statin-intolerant patients, subcutaneous administration of a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels and was associated with short-term tolerability.

  • 20.
    Maccubbin, Darbie L
    et al.
    Merck Sharp and Dohme Corp, NJ USA .
    Chen, Fabian
    Merck Sharp and Dohme Corp, NJ USA .
    Weimer Anderson, Jennifer
    Merck Sharp and Dohme Corp, NJ USA .
    Sirah, Waheeda
    Merck Sharp and Dohme Corp, NJ USA .
    McCrary Sisk, Christine
    Merck Sharp and Dohme Corp, NJ USA .
    Kher, Uma
    Merck Sharp and Dohme Corp, NJ USA .
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Bays, Harold E
    Louisville Metab and Atherosclerosis Research Centre, KY USA .
    Mitchel, Yale B
    Merck Sharp and Dohme Corp, NJ USA .
    Effectiveness and Safety of Laropiprant on Niacin-Induced Flushing2012Ingår i: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 110, nr 6, s. 817-822Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Extended-release niacin (ERN) improves multiple lipid parameters but is underused owing to niacin-induced flushing (NIF). Laropiprant (LRPT) reduces NIF; however, its effects on chronic flushing (andgt;6 months) have not been studied. We examined whether after 20 weeks of treatment with ERN/LRPT, patients who continued ERN/LRPT would experience less NIF than patients who stopped LRPT and continued ERN alone. A total of 1,152 dyslipidemic patients were randomized 2:2:1 to group 1, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks and then ERN/LRPT 2 g/40 mg/day from 5 to 32 weeks; group 2, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks, ERN/LRPT 2 g/40 mg/day from 5 to 20 weeks, and then ERN 2 g/day without LRPT from 21 to 32 weeks; or group 3, placebo for the entire study. The end points included the number of days each week with a moderate or greater Global Flushing Severity Score (GFSS) andgt;= 4 (primary end point) and the percentage of patients with a maximum GFSS of andgt;= 4 (secondary end point) during the postwithdrawal period (weeks 21 to 32). ERN/LRPT produced significantly less NIF than ERN alone during the postwithdrawal period, as measured by the number of days each week with a GFSS of andgt;= 4 (p andlt; 0.001) and the percentage of patients with a maximum GFSS of andgt;= 4 (p andlt; 0.001; ERN/LRPT 19.6%; ERN 48.9%; placebo 9.2%). Compared with ERN alone, ERN/LRPT produced fewer drug-related adverse experiences during the postwithdrawal period. After 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less NIF than did patients who had had LRPT withdrawn and had continued with ERN alone. In conclusion, the results of our study support the long-term efficacy of ERN/LRPT in reducing NIF symptoms.

  • 21.
    Schwartz, Gregory G
    et al.
    University of Colorado, CO USA Vet Affairs Medical Centre, CO USA .
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Abt, Markus
    F Hoffmann La Roche, Switzerland .
    Ballantyne, Christie M
    Baylor Coll Med, TX 77030 USA Methodist DeBakey Heart and Vasc Centre, TX 77030 USA .
    Barter, Philip J
    Heart Research Institute, Australia .
    Brumm, Jochen
    F Hoffmann La Roche, Switzerland .
    Chaitman, Bernard R
    St Louis University, MO 63103 USA .
    Holme, Ingar M
    Oslo University Hospital, Norway .
    Kallend, David
    F Hoffmann La Roche, Switzerland .
    Leiter, Lawrence A
    University of Toronto, Canada .
    Leitersdorf, Eran
    Hadassah Hebrew University, Israel .
    McMurray, John J V
    University of Glasgow, Scotland .
    Mundl, Hardi
    F Hoffmann La Roche, Switzerland .
    Nicholls, Stephen J
    University of Adelaide, Australia .
    Shah, Prediman K
    Cedars Sinai Heart Institute, CA USA .
    Tardif, Jean-Claude
    University of Montreal, Canada .
    Wright, R Scott
    Mayo Clin, MN USA .
    Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome2012Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 367, nr 22, s. 2089-2099Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND less thanbrgreater than less thanbrgreater thanIn observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes. less thanbrgreater than less thanbrgreater thanMETHODS less thanbrgreater than less thanbrgreater thanWe randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation. less thanbrgreater than less thanbrgreater thanRESULTS less thanbrgreater than less thanbrgreater thanAt the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P = 0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (Pandlt;0.001 for both comparisons). less thanbrgreater than less thanbrgreater thanCONCLUSIONS less thanbrgreater than less thanbrgreater thanIn patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.)

  • 22.
    Kee Ryu, Sung
    et al.
    Eulji University.
    Mallat, Ziad
    University of Cambridge.
    Benessiano, Joelle
    Paris Descartes University.
    Tedgui, Alain
    Paris Descartes University.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Bao, Weihang
    Pfizer Inc.
    Schwartz, Gregory G
    University of Colorado.
    Tsimikas, Sotirios
    University of Calif San Diego.
    Phospholipase A(2) Enzymes, High-Dose Atorvastatin, and Prediction of Ischemic Events After Acute Coronary Syndromes2012Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, nr 6, s. 757-U71Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-Secretory phospholipase A2 (sPLA(2)) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are enzyme biomarkers of increased cardiovascular risk and targets of emerging therapeutic agents. Their relationship to cardiovascular events in the setting of high-dose statin therapy compared with placebo in patients with acute coronary syndrome is not known. less thanbrgreater than less thanbrgreater thanMethods and Results-sPLA(2) and Lp-PLA(2) mass and activity were measured in 2587 patients in the Myocardial Ischemia Reduction With Acute Cholesterol Lowering (MIRACL) trial at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. Baseline levels of sPLA(2) and Lp-PLA(2) mass and activity were not associated with the primary efficacy measure of the trial of death, myocardial infarction, or unstable angina. However, in the overall cohort, baseline sPLA(2) mass predicted risk of death after multivariable adjustment (hazard ratio for 2-fold increase, 1.30; 95% confidence interval, 1.09 -1.56; P = 0.004). This association remained significant when examined separately in the placebo group but not in the atorvastatin group. Compared with placebo, atorvastatin reduced median sPLA(2) mass (-32.1% versus -23.1%), sPLA(2) activity (-29.5% versus -19.2%), Lp-PLA(2) mass (-35.8% versus -6.2%), and Lp-PLA(2) activity (-24.3% versus 5.4%; P andlt; 0.001 for all). Atorvastatin reduced the hazard of death associated with elevated sPLA(2) mass and activity by approximate to 50%. less thanbrgreater than less thanbrgreater thanConclusions-sPLA(2) mass independently predicts death during a 16-week period after acute coronary syndrome. High-dose atorvastatin significantly reduces sPLA(2) and Lp-PLA(2) mass and activity after acute coronary syndrome and mitigates the risk of death associated with sPLA(2) mass. Atorvastatin may exert antiinflammatory effects on phospholipases that contribute to its therapeutic benefit after acute coronary syndrome.

  • 23.
    Tikkanen, Matti J.
    et al.
    University of Helsinki.
    Fayyad, Rana
    Pfizer Inc, New York.
    Laskey, Rachel
    Pfizer Inc, New York.
    Holme, Ingar
    Oslo University Hospital.
    Faergeman, Ole
    Aarhus University Hospital.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Lindahl, Christina
    Pfizer Sweden, Sollentuna.
    Kastelein, John J.
    Academic Hospital Amsterdam.
    Larsen, Mogens Lytken
    Aarhus University Hospital.
    Pedersen, Terje R.
    Oslo University Hospital.
    Among CHD Patients in the IDEAL Study, Those with Elevated Levels of Alanine Aminotransferase at Baseline Had a Lower Rate of Major Coronary Events in CIRCULATION, vol 124, issue 21, pp2011Ingår i: CIRCULATION, American Heart Association , 2011, Vol. 124, nr 21Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 24.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Diskussionen om vad som ska vara målet för lipidsänkning fortsätter: Expertrådet - en stoppkloss för modern kardiovaskulär prevention: [The discussion on target goals in lipid reduction is still going on. The expert committee - a block for current cardiovascular prevention]2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 47, s. 2443-Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 25.
    Chen, Fabian
    et al.
    Merck, Clin, Whitehouse Stn, NJ USA .
    Maccubbin, Darbie
    Merck, Clin, Whitehouse Stn, NJ USA .
    Weimer Anderson, Jennifer
    Merck, Clin, Whitehouse Stn, NJ USA .
    McCrary Sisk, Christine
    Merck, GSMP, Whitehouse Stn, NJ USA.
    Kher, Uma
    Merck, Stat, Whitehouse Stn, NJ USA .
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Bays, Harold E
    L MARC, Louisville, KY USA .
    Following Stable Therapy with Extended Release Niacin/Laropiprant, Continued Extended Release Niacin/Laropiprant Use Reduced Flushing versus Extended Release Niacin Alone in Dyslipidemic Patients in CIRCULATION, vol 124, issue 21, pp2011Ingår i: CIRCULATION, American Heart Association , 2011, Vol. 124, nr 21Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 26.
    Olsson, Anders
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Lindahl, Christina
    Pfizer Sweden.
    Holme, Ingar
    Oslo University Hospital.
    Fayyad, Rana
    Pfizer Inc.
    Faergeman, Ole
    Arhus University Hospital.
    Kastelein, John J P
    Academic Hospital Amsterdam.
    Tikkanen, Matti J
    Helsinki University Hospital.
    Lytken Larsen, Mogens
    Arhus University Hospital.
    R Pedersen, Terje
    Oslo University Hospital.
    LDL cholesterol goals and cardiovascular risk during statin treatment: the IDEAL study2011Ingår i: EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION and REHABILITATION, ISSN 1741-8267, Vol. 18, nr 2, s. 262-269Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: We assessed the proportion of patients treated with either simvastatin 20 or 40 mg or atorvastatin 80 mg who achieved low-density lipoprotein cholesterol (LDL-C) goals of 2.5 or 2.0 mmol/l in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study. We explored how lipoprotein components related to cardiovascular disease (CVD) outcomes in these groups. Methods and results: For subjects who reached on-treatment LDL-C goals, Cox regression models were used to assess the ability of lipoprotein components to predict CVD events. Treatment with simvastatin or atorvastatin resulted in 40 per cent and 80 per cent of patients, respectively, reaching the 2.5 mmol/l goal and 12 per cent and 52 per cent, respectively, reaching the 2.0 mmol/l goal, after 1 year (all p andlt; 0.001 between groups). Adjusting for baseline LDL-C levels, hazard ratio (HR) for those reaching 2.0-2.5 mmol/l LDL-C versus those reaching andlt; 2.0 mmol/l was 1.16 (95% confidence interval [CI], 1.02-1.33, p = 0.023). An increase of the apolipoprotein B/A1 (apoB/A1) ratio by 1 standard deviation in participants who reached 2.0 mmol/l showed a HR for CVD of 1.14 (95% CI, 1.04-1.25, p = 0.004). Conclusion: More CVD patients treated with atorvastatin than simvastatin achieved either LDL-C goal and those reaching the 2.0 mmol/l goal exhibited significantly less CVD than those only reaching 2.5 mmol/l. In those reaching the 2.0 mmol/l goal, the apoB/A1 ratio still bears a relation to CVD outcome. The use of apoB/A1 ratio may provide additional predictive value to that of LDL-C.

  • 27.
    Olsson, Anders G.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Målvärden för LDL-kolesterol har satts ur spel. Kolesterolet bör sänkas maximalt vid hög kardiovaskulär risk: [Target levels for LDL cholesterol are put out of the running. Cholesterol should be lowered maximally in high cardiovascular risk]2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 22-23, s. 1240-1243Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [sv]

    En utökad metaanalys från Cholesterol Treatment Trialists’ (CTT) Collaboration har inkluderat fem studier av lågdos vs högdos statin med totalt 170 000 deltagare.

    Här visades att ytterligare 1 mmol/l sänkning av LDL-kolesterol på ett säkert sätt minskar risken för stora kar­dio­vaskulära händelser med 22 procent, oavsett ini­tialt LDL-kolesterolvärde.

    Patienter med hög risk för kardiovaskulära händelser har nytta av intensiv statinbehandling även om LDL-kolesterolvärdet är <2 mmol/l.

    IDEAL-studien pekar på sjukdomsvinster med statinbehandling som ger LDL-kole­sterol <2,0 mmol/l.

    En översyn av målvärdet för LDL-kolesterol i sekundär prevention bör göras. Dessutom ska alla högriskpatienter som redan har <2 mmol/l LDL-kolesterol statinbehandlas.

    Simvastatin i dosen 80 mg dagligen bör dock undvikas på grund av risk för muskelbiverkningar.

  • 28.
    Olsson, Anders G
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Statin efter intracerebral blödning bör ifrågasättas: Subgruppsanalyser visar på ökad risk för ny blödning2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 24-25, s. 1297-1298Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [sv]

    I två interventionsstudier visar subgruppsanalys att patienter med tidigare stroke som behandlas med statin drabbas av intracerebral blödning i högre grad än placebobehandlade.

    I en beslutsanalys har visats att patienter som haft lobär intracerebral blödning men inte kardiovaskulär sjukdom får 2,2 fler kvalitetsjusterade levnadsår genom att undvika statinbehandling.

    Kliniker bör noga, mot bakgrund av patientens övriga risksituation, överväga om statinbehandling är motiverad till patienter med genomgången intracerebral blödning, framför allt av lobär karaktär.

  • 29.
    Holme, I
    et al.
    Oslo University Hospital.
    Fayyad, R
    Pfizer Inc.
    Faergeman, O
    Arhus University Hospital.
    Kastelein, J J P
    Acad Hospital.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Tikkanen, M J
    University Helsinki.
    Larsen, M L
    Arhus University Hospital.
    Lindahl, C
    Pfizer Sweden.
    Holdaas, H
    University of Oslo.
    Pedersen, T R
    Oslo University Hospital.
    Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: results from the IDEAL trial2010Ingår i: JOURNAL OF INTERNAL MEDICINE, ISSN 0954-6820, Vol. 267, nr 6, s. 567-575Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: Results from the IDEAL trial. J Intern Med 2010; 267:567-575. Objectives. In Incremental Decrease in Endpoints through Aggressive Lipid-lowering (IDEAL), we compared cardiovascular outcomes in patients with and without chronic kidney disease (CKD) (estimated glomerular filtration rate andlt; 60 mL min-1 1.73 m-2) and analysed relationships between lipoprotein components (LC) and major coronary events (MCE) and other cardiovascular (CV) events. Design. Exploratory analysis of CV endpoints in a randomized trial comparing high dose of atorvastatin to usual dose of simvastatin on MCE. Settings. Patients with CKD were compared with the non-CKD patients. Cox regression models were used to study the relationships between on-treatment levels of LC and incident MCE. Findings. Chronic kidney disease was strongly associated with cardiovascular end-points including total mortality. In patients with CKD, a significant benefit of high dose atorvastatin treatment was found for any CV events, stroke and peripheral artery disease, but not for MCE. However, all cardiovascular end-points except stroke and CV mortality were reduced in the non-CKD group. Differential changes in LC or relationships to LC could not explain the different treatment outcomes in MCE in the two groups. Interpretation. Chronic kidney disease was a powerful risk factor for all cardiovascular end-points. The reason why the significant reductions achieved by high-dose statin treatment in most CV end-points in the non-CKD group were only in part matched by similar reductions in the CKD patients is not apparent. This difference did not result from differential changes in or relations to LC, but limited power may have increased the possibility of chance findings.

  • 30.
    Pedersen, Terje R
    et al.
    Oslo University Hospital.
    Cater, Nilo B
    Pfizer Inc.
    Faergeman, Ole
    Arhus University Hospital.
    Kastelein, John J P
    Acad Hospital Amsterdam.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Tikkanen, Matti J
    Helsinki University Hospital.
    Holme, Ingar
    Oslo University Hospital.
    Lytken Larsen, Mogens
    Arhus University Hospital.
    Lindahl, Christina
    Pfizer Sweden.
    Szarek, Michael
    Pfizer Inc.
    Comparison of Atorvastatin 80 mg/day Versus Simvastatin 20 to 40 mg/day on Frequency of Cardiovascular Events Late (Five Years) After Acute Myocardial Infarction (from the Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] Trial)2010Ingår i: AMERICAN JOURNAL OF CARDIOLOGY, ISSN 0002-9149, Vol. 106, nr 3, s. 354-359Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous studies have demonstrated that benefits of intensive statin therapy compared to standard statin therapy begin shortly after an acute event and are continued up to 2 years of follow-up. However, whether efficacy and safety of intensive statin therapy in patients with a recent cardiac event are maintained in longer-term follow-up has not been evaluated. We conducted a post hoc analysis of a subgroup of 999 patients who had a first acute myocardial infarction (MI) andlt;2 months before randomization in a prospective, open-label, blinded end-point evaluation trial of 8,888 patients with a history of MI that compared intensive statin therapy (atorvastatin 80 mg) to standard statin therapy (simvastatin 20 to 40 mg) over approximately 5 years of follow-up. We analyzed the same composite end point used in the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trial (death, MI, hospitalization for unstable angina, revascularization, and stroke). Rates of the composite end point were 44.7% (n = 226) in the simvastatin group and 37.9% (n = 187) in the atorvastatin group (hazard ratio 0.82, 95% confidence interval 0.67 to 0.99, p = 0.04). Although statistical power was smaller than that of the PROVE IT trial, the relative risk decrease observed at 5 years is consistent with that in the 2-year follow-up in PROVE IT. The 2 treatment regimens were well tolerated. In conclusion, our analysis provides support for the strategy of placing patients with recent MI on intensive statin therapy and maintaining the high dose over the long term, beyond 2 years.

  • 31.
    Olsson, Anders
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Lindahl, C
    Pfizer Sweden.
    Holme, I
    Oslo University Hospital.
    Fayyad, R
    Pfizer Inc.
    Faergeman, O
    Aarhus University Hospital,.
    Kastelein, J
    Academic Hospital, Amsterdam.
    Tikkanen, M
    Helsinki University Hospital.
    Lytken Larsen, M
    Aarhus University Hospital.
    Pedersen, T
    Oslo University Hospital.
    CORONARY PATIENTS REACHING LDL-CHOLESTEROL andlt; 2.0 mmol/L HAVE THE LOWEST RISK OF CARDIOVASCULAR EVENTS DURING STATIN TREATMENT: THE IDEAL STUDY in ATHEROSCLEROSIS SUPPLEMENTS, vol 11, issue 2, pp 53-532010Ingår i: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2010, Vol. 11, nr 2, s. 53-53Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 32.
    Olsson, Anders G
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    HDL and LDL as therapeutic targets for cardiovascular disease prevention: The possible role of niacin2010Ingår i: NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES, ISSN 0939-4753, Vol. 20, nr 8, s. 553-557Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recently two studies on the effect of addition of extended-release niacin to statin treatment on measures of carotid atherosclerosis were estimated in the ARBITER 6-HALTS study (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies) study and the Oxford Niacin Study were published. Adding niacin to statin treatment significantly diminished carotid atherosclerosis as measured by ultrasound carotid intima-media thickness or magnetic resonance imaging. An inhibitor of niacin induced flushing, laropiprant has been developed and demonstrated to considerably improve the tolerability of niacin therapy without impeding on its effect on lipoproteins. Still however clear evidence for the clinical benefit of long-term niacin treatment on cardiovascular morbidity and mortality is lacking. The development situation for ezetimibe is similar to that of niacin. Long-term interventional studies with hard endpoints of both therapies are ongoing. Also both drugs, when proven efficient and safe, are eagerly needed in the prevention of cardiovascular disease.

  • 33.
    Olsson, Anders
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Rosengren, A.
    Avdelningen för akut och kardiovaskulär medicin, Sahlgrenska akademin, Göteborg, Sweden.
    Tornvall, P.
    Svenska cardiologföreningen, hjärtkliniken, Karolinska Universitetssjukhuset, Stockholm, Sweden.
    Kolesterolhypotesen står sig2010Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 12, s. 831-836Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Då kolesterolhypotesen nyligen ifrågasatts har en uppdatering gjorts av kolesterolets roll i aterogenesen hos människa.

    Genetiska, epidemiologiska, cellbiologiska, molekylärbiologiska och kliniska skäl som anförs visar entydigt på en viktig roll för low-density lipoprotein (LDL) i aterosklerosutvecklingen.

    Behandlingsstudier med olika typer av LDL-sänkande behandling styrker ytterligare att kolesterol har stor betydelseför uppkomsten av atero­skleros.

    Fortfarande kvarstår en stor risk för hjärt–kärlsjukdom i Sverige. Nya hypoteser kring orsaken till ateroskleros är därför välkomna.

    Nya tankar kan vara att optimal LDL-nivå ännu inte uppnåtts och/eller att andra lipoproteiner, såsom high-density lipoprotein (HDL) eller triglycerider också måste tas med som viktiga aterogena faktorer.

  • 34.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Laropiprant plus niacin for dyslipidemia and prevention of cardiovascular disease2010Ingår i: Expert Opinion on Pharmacotherapy, ISSN 1465-6566, E-ISSN 1744-7666, Vol. 11, nr 10, s. 1715-1726Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Importance of the field: Prevention of cardiovascular disease has been only partially successful with the use of cholesterol-lowering drugs like statins. There is a residual risk remaining, which may be addressed by increasing protective high-density lipoprotein (HDL) cholesterol and apolipoprotein A1. The best drug available for that purpose is niacin. In addition to increasing HDL cholesterol and apolipoprotein A1, niacin decreases triglycerides, low-density lipoprotein (LDL)-cholesterol and lipoprotein(a) and has been named the broad-spectrum lipid drug. Areas covered in this review: This review summarizes to what extent a new formulation of niacin may meet this request. The effects of niacin on lipoproteins, atherosclerosis and cardiovascular disease are described, from its first publication in 1955, and also its mechanism of action on lipoproteins and on flushing. The flushing inhibitor laropiprant is described as well as the antiflushing effect of this compound when added to extended-release niacin. What the reader will gain: The reader will gain knowledge of the development of niacin as an antiatherosclerosis treatment and of the added value that laropiprant may offer this treatment principle; and also the present place of niacin/laropiprant in the armamentarium of cardiovascular preventive drugs. Take home message: Niacin/laropiprant is a welcome means to address the residual risk in high-risk patients on statin therapy. However, the drug combination cannot completely eliminate niacin-induced side effects. Prescribing this treatment, therefore, will require careful provision of information and instruction to the patient.

  • 35.
    Olsson, Anders
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Rosengren, A.
    Sahlgrenska akademin, Göteborg.
    Tornvall, P.
    Karolinska universitetssjukhuset.
    Patienten framför allt!2010Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 24, s. 1639-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    [No abstract available]

  • 36.
    L Ohsfeldt, R
    et al.
    Department Hlth Policy and Management, College Stn, USA.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Jensen, M M
    AstraZeneca.
    Gandhi, S K
    AstraZeneca.
    Paulsson, T
    AstraZeneca.
    The cost-effectiveness of rosuvastatin 20 mg for the prevention of cardiovascular morbidity and mortality - a swedish economic evaluation of the JUPITER trial in EUROPEAN HEART JOURNAL, vol 31, issue , pp 225-2252010Ingår i: EUROPEAN HEART JOURNAL, Oxford University Press , 2010, Vol. 31, s. 225-225Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 37.
    Ladenson, Paul W
    et al.
    Johns Hopkins University.
    Kristensen, Jens D
    Karo Bio.
    Ridgway, E Chester
    University of Colorado.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Carlsson, Bo
    Karo Bio.
    Klein, Irwin
    N Shore University Hospital.
    Baxter, John D
    Methodist Hospital.
    Angelin, Bo
    Karolinska University Hospital.
    Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated Dyslipidemia2010Ingår i: NEW ENGLAND JOURNAL OF MEDICINE, ISSN 0028-4793, Vol. 362, nr 10, s. 906-916Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Dyslipidemia increases the risk of atherosclerotic cardiovascular disease and is incompletely reversed by statin therapy alone in many patients. Thyroid hormone lowers levels of serum low-density lipoprotein (LDL) cholesterol and has other potentially favorable actions on lipoprotein metabolism. Consequently, thyromimetic drugs hold promise as lipid-lowering agents if adverse effects can be avoided. METHODS We performed a randomized, placebo-controlled, double-blind, multicenter trial to assess the safety and efficacy of the thyromimetic compound eprotirome (KB2115) in lowering the level of serum LDL cholesterol in patients with hypercholesterolemia who were already receiving simvastatin or atorvastatin. In addition to statin treatment, patients received either eprotirome (at a dose of 25, 50, or 100 mu g per day) or placebo. Secondary outcomes were changes in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Patients were monitored for potential adverse thyromimetic effects on the heart, bone, and pituitary. RESULTS The addition of placebo or eprotirome at a dose of 25, 50, or 100 mu g daily to statin treatment for 12 weeks reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively, (mean reduction from baseline, 7%, 22%, 28%, and 32%). Similar reductions were seen in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Eprotirome therapy was not associated with adverse effects on the heart or bone. No change in levels of serum thyrotropin or triiodothyronine was detected, although the thyroxine level decreased in patients receiving eprotirome. CONCLUSIONS In this 12-week trial, the thyroid hormone analogue eprotirome was associated with decreases in levels of atherogenic lipoproteins in patients receiving treatment with statins.

  • 38.
    Ladenson, Paul W
    et al.
    Johns Hopkins University.
    Kristensen, Jens D
    Karo Bio AB.
    Ridgway, E Chester
    University of Colorado.
    Olsson, Anders G
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Carlsson, Bo
    Klein, Irwin
    Baxter, John D
    Angelin, Bo
    Karolinska Institutet.
    Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated Dyslipidemia2010Ingår i: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 65, nr 8, s. 512-513Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Statins effectively reduce levels of serum cholesterol and lower the risk of cardiovascular disease, but have limited effectiveness if stringent goals for serum low-density lipoprotein (LDL) cholesterol levels are not met or adverse effects develop, requiring a dose reduction or drug discontinuation. Previous studies have shown that thyroid hormone and some of its metabolites reduce levels of serum LDL cholesterol and have potentially favorable actions on other lipoproteins. The studies were discontinued because of reports of adverse effects on heart and bone, and possible deaths. In a recent report, eprotirome, a thyromimetic compound with minimal uptake in nonhepatic-tissues, was shown to reduce levels of serum total and LDL cholesterol and apolipoprotein B without apparent side effects in patients not receiving statin therapy. This randomized, placebo-controlled, double-blind, multicenter trial investigated the safety and efficacy of eprotirome in lowering the level of serum LDL cholesterol in patients with hypercholesterolemia who already were receiving simvastatin or atorvastatin. The aim of the study was to determine whether adding eprotirome to statin therapy would provide additional lipid-lowering actions without producing adverse extrahepatic thyromimetic effects. Patients were randomly assigned to receive daily oral doses of 25, 50, or 100 mcg of eprotirome or a placebo for 12 weeks. The primary study outcome was changes in serum LDL cholesterol. The potential adverse thyromimetic effects on the heart, bone, and pituitary were examined. Treatment of patients for 12 weeks already receiving statins with either placebo or eprotirome at a dose of 25, 50, or 100 mu g reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) at baseline to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively; this represented a mean reduction from baseline of 7%, 22%, 28%, and 32%, respectively. Similar reductions were found in the secondary study outcomes, which included serum levels of apolipoprotein B, triglycerides, and Lp(a) lipoprotein. No evidence of adverse effects of eprotirome on the heart, bone, or pituitary was noted. Although reductions in serum levels of thyroxine occurred in some patients who received eprotirome, there were no changes in levels of thyrotropin or triiodothyronine. These findings demonstrate that the addition of eprotirome to statin therapy produces substantial further reductions in serum LDL cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B. The drug appears to have an excellent safety profile.

  • 39.
    Holme, Ingar
    et al.
    Oslo University Hospital.
    Szarek, Michael
    Cater, Nilo B
    Pfizer Inc.
    Faergeman, Ole
    Pfizer Inc.
    Kastelein, John J P
    University of Amsterdam.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Tikkanen, Matti J
    Helsinki University Hospital.
    Lytken Larsen, Mogens
    Arhus University Hospital.
    Lindahl, Christina
    Pfizer Sweden.
    Pedersen, Terje R
    Oslo University Hospital.
    Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study2009Ingår i: EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION and REHABILITATION, ISSN 1741-8267, Vol. 16, nr 3, s. 315-320Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The Incremental Decrease in End Points through Aggressive Lipid Lowering trial showed that the primary endpoint major coronary event was reduced by 11% (0.78-1.01) using atorvastatin 80 mg versus simvastatin 20-40 mg in patients with coronary heart disease (P=0.07). Adherence was high in both treatment groups but significantly higher in patients treated with simvastatin. Design The Incremental Decrease in End Points through Aggressive Lipid Lowering was a prescription trial with a prospective randomized open label endpoint evaluation. Methods and results Adherence was calculated as exposure time on prescribed drugs divided by total follow-up time until death or end of follow-up and was a potential confounder. Adjusting for categorical adherence below or above 80% by two methods revealed that the relative risk reduction of the primary endpoint was more in the region of 15% (P=0.02) than 11% as found unadjusted. Censoring at the first occurrence of a cardiovascular event rather than at death increased this estimate to 17% (P=0.02). Noncardiovascular mortality was reduced on atorvastatin treatment by 21% (1-37%) after adjustment for adherence, whereas such reduction was not observed for cardiovascular mortality. Conclusion This study found that the difference in adherence between treatment groups may have underestimated the true effect of the treatment differential. Usage of prospective randomized open label endpoint evaluation design should be carefully considered when well-known treatments are compared with rather new ones and especially in segments where patients could be more vulnerable, as in the elderly. Nonadherers in a clinical trial may be at especially high risk of fatal and nonfatal endpoints from various diseases and should be carefully monitored.

  • 40.
    Olsson, Anders
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Lindahl, C
    Stockholm County Council, Stockholm, Sweden .
    Fayyad, R
    Pfizer Inc, New York, USA.
    Bhatia, S
    Pfizer Inc, New York, USA.
    Holme, I
    Oslo University Hospital, Oslo.
    CAN LIPID/APOLIPOPROTEIN FACTORS ACCOUNT FOR RESIDUAL RISK IN PATIENTS ATTAINING CURRENT LDL-C TARGETS?2009Ingår i: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier, 2009, Vol. 10, nr 2, s. e1214-e1214Konferensbidrag (Övrigt vetenskapligt)
  • 41.
    Strandberg, Timo E
    et al.
    University of Oulu.
    Holme, Ingar
    Ullevaal University Hospital.
    Faergeman, Ole
    Arhus University Hospital.
    Kastelein, John J P
    University of Amsterdam.
    Lindahl, Christina
    Pfizer Swedeb.
    Lytken Larsen, Mogens
    Arhus University Hospital.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Pedersen, Terje R
    Ullevaal University Hospital.
    J Tikkanen, Matti
    Comparative Effect of Atorvastatin (80 mg) Versus Simvastatin (20 to 40 mg) in Preventing Hospitalizations for Heart Failure in Patients With Previous Myocardial Infarction2009Ingår i: AMERICAN JOURNAL OF CARDIOLOGY, ISSN 0002-9149, Vol. 103, nr 10, s. 1381-1385Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We investigated whether intensive cholesterol lowering could more effectively prevent heart failure (HF) in secondary prevention. The IDEAL study was a 4.8-year prospective, randomized trial comparing "usual" simvastatin treatment (20 to 40 mg/day, n = 4,449) with high-dose atorvastatin (80 mg/day, n = 4,439) in patients with a history of myocardial infarction (MI). At baseline, 94% of patients (n = 8,351) had no history of HF. During the course of the trial, there were 222 new or recurrent hospitalizations for HF (57 and 165 in those with and without HF at baseline, respectively), 123 (2.8%) in the simvastatin group and 99 (2.2%) in the atorvastatin group (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.62 to 1.05, p = 0.11). After adjustments, atorvastatin 80 mg was associated with a 26% decrease of new HF events compared with simvastatin 20 to 40 mg (HR 0.74, 95% CI 0.57 to 0.97, p = 0.03). Atorvastatin tended to be associated with fewer HF events in those with HF at baseline (n = 537, HR 0.65, 95% CI 0.38 to 1.11, p = 0.11) and those without HF at baseline (n = 8,351, HR 0.80, 95% CI 0.59 to 1.09, p = 0.15). Also, HF without preceding MI (n = 187) was decreased (HR 0.73, 95% CI 0.54 to 0.97, p = 0.03). In conclusion, atorvastatin 80 mg was more efficient than simvastatin 20 to 40 mg in preventing development of HF in patients with previous MI.

  • 42.
    Tikkanen, M.J.
    et al.
    Helsinki University Central Hospital.
    Holme, I.
    Ullevål University Hospital.
    Cater, N.B.
    Pfizer Inc.
    Szarek, M.
    Pfizer Inc.
    Faergeman, O.
    Århus University Hospital.
    Kastelein, J.J.P.
    Academic Hospital Amsterdam.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Larsen, M.L.
    Århus University Hospital.
    Lindahl, C.
    Pfizer Sweden.
    Pedersen, T.R.
    Ullevål University Hospital.
    Comparison of Efficacy and Safety of Atorvastatin (80 mg) to Simvastatin (20 to 40 mg) in Patients Aged less than65 Versus =65 Years With Coronary Heart Disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] Study)2009Ingår i: American Journal of Cardiology, ISSN 0002-9149, Vol. 103, nr 5, s. 577-582Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The efficacy and safety of atorvastatin (80 mg/day) versus simvastatin (20 to 40 mg/day) in older (age =65 years) versus younger (less than65 years) patients were assessed in a prespecified secondary analysis of the 8,888 patients with myocardial infarction in the IDEAL trial, a randomized open-label study. Several cardiovascular end points were evaluated, including the occurrence of a first major coronary event (MCE; nonfatal myocardial infarction, coronary heart disease death, or resuscitated cardiac arrest), the primary end point of the trial, and occurrence of any cardiovascular event (MCE, stroke, revascularization, unstable angina, congestive heart failure, and peripheral artery disease). Although there were no significant interactions between age and treatment, the magnitude of effect in favor of atorvastatin was higher in younger versus older patients (occurrence of first MCE, hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.66 to 0.98; and HR 0.95, 95% CI 0.80 to 1.15, respectively; occurrence of any cardiovascular (CV) event, HR 0.80, 95% CI 0.71 to 0.89; and HR 0.88, 95% CI 0.79 to 0.99, respectively). These results were likely influenced by adherence, which was lower in older patients and those receiving atorvastatin compared with those receiving simvastatin. Rates of any reported serious adverse event were higher in older patients, but did not differ between the 2 statin groups. In conclusion, except for any CV events in the older group, significant reductions in primary and secondary end points were observed only in patients less than65 years of age. The safety of atorvastatin (80 mg) and simvastatin (20 to 40 mg) was similar in patients aged less than65 and greater than65 years with stable coronary disease.

  • 43.
    Holme, Ingar
    et al.
    Ullevaal University Hospital.
    E Strandberg, Timo
    University of Oulu.
    Faergeman, Ole
    Arhus University Hospital.
    Kastelein, John J P
    University of Amsterdam.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Tikkanen, Matti J
    University of Helsinki.
    Lytken Larsen, Mogens
    Arhus University Hospital.
    Lindahl, Christina
    Pfizer Sweden.
    Pedersen, Terje R
    Ullevaal University Hospital.
    Congestive heart failure is associated with lipoprotein components in statin-treated patients with coronary heart disease Insights from the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL)2009Ingår i: ATHEROSCLEROSIS, ISSN 0021-9150, Vol. 205, nr 2, s. 522-527Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Very few, if any, studies have assessed the ability of apolipoproteins to predict new-onset of congestive heart failure (HF) in statin-treated patients with coronary heart disease (CHD). Aims: To employ the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL) study database to assess the association of on-treatment lipoprotein components with prediction of HF events and to compare their predictive value with that of established risk factors such as hypertension and diabetes. Methods: We used Cox regression models to study the relationships between on-treatment levels of apolipoproteins A1 and B to subsequent HE Chi square information value from the log likelihood was used to compare the predictive value of lipoprotein components with established risk factors of HF. Findings: In the IDEAL study, on-treatment apolipoproteins proved to be associated with the occurrence of new-onset HE Variables related to low-density lipoprotein cholesterol (LDL-C) carried less predictive information than those related to high-density lipoprotein cholesterol (HDL-C), and apoA-1 was the single variable most strongly associated with HF. LDL-C was less predictive than both non-HDL-C (total cholesterol minus HDL-C) and apoB. The ratio of apoB to apoA-1 was most strongly related to HF after adjustment for potential confounders, among which diabetes had a stronger correlation with HF than did hypertension. ApoB/apoA-1 carried approximately 2.2 times more of the statistical information value than that of diabetes. Calculation of the net reclassification improvement index revealed that about 3.7% of the patients had to be reclassified into more correct categories of risk once apoB/apoA-1 was added to the adjustment factors. The reduction in risk by intensive lipid-lowering treatment as compared to usual-dose simvastatin was well predicted by the difference in apoB/apoA-1 on-treatment levels. Interpretation: The on-treatment ratio of apoB/apoA-1 was the strongest predictor of HF in CHD patients of both IDEAL treatment arms combined, mostly driven by the strong association with apoA-1, whereas LDL-C and non-HDL-C were less able to predict HF outcome. The predictive information value contained within apoB/apoA-1 was about 2.2 times more than that of diabetes. Between-treatment group differences in HF were to a significant extent explained by on-treatment differences in apoB/apoA-1, mostly through the changes in apoB. We argue therefore, on-treatment lipoprotein components contribute to the overall future risk of HF in statin-treated patients with CHD.

  • 44.
    Chisalita, Simona Ioana
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken.
    Lindström, Torbjörn
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Eson Jennersjö, Pär
    Borensberg Health Centre, Linköping.
    Paulsson, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Westermark, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Arnqvist, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control2009Ingår i: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 46, nr 1, s. 35-42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our aim was to study, at the same glycemic control, how treatment with either the insulin secretagogue repaglinide or exogenous insulin aspart affects endogenous insulin secretion, plasma insulin and IAPP (islet amyloid polypeptide) levels, GH-IGF (growth hormone-insulin-like growth factor) axis and plasma lipoprotein concentrations in patients with type 2 diabetes. Five patients, age 65.0 +/- A 4.1 years (mean +/- A SE), body weight 82.5 +/- A 5.0 kg, BMI (body mass index) 27.7 +/- A 1.5 kg/m(2) were treated for 10 weeks with repaglinide or insulin aspart in a randomized, cross-over study. At the end of each treatment a 24-h metabolic profile was performed. Blood glucose, C-peptide, free human insulin, free total (human and analogue) insulin, proinsulin, IAPP, IGF-I, IGFBP-1 (IGF binding protein-1), GHBP (growth hormone binding protein) and plasma lipoprotein concentrations were measured. Similar 24-h blood glucose profiles were obtained with repaglinide and insulin aspart treatment. During the repaglinide treatment, the meal related peaks of C-peptide and free human insulin were about twofold higher than during treatment with insulin aspart. Proinsulin, GHBP were higher and IAPP levels tended to be higher during repaglinide compared to insulin aspart. Postprandial plasma total cholesterol, triglycerides and apolipoprotein B concentrations were higher on repaglinide than on insulin aspart treatment. Our results show that, at the same glycemic control, treatment with exogenous insulin aspart in comparison with the insulin secretagogue repaglinide result in a lower endogenous insulin secretion, and a tendency towards a less atherogenic postprandial lipid profile.

  • 45.
    Kinlay, Scott
    et al.
    Brigham & Womens Hospital.
    Schwartz, Gregory G
    Vet Affairs Med Centre.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Rifai, Nader
    Harvard University.
    Bao, Weihang
    Pfizer Pharmaceuticals Group.
    Libby, Peter
    Brigham & Womens Hospital.
    Ganz, Peter
    San Francisco General Hospital.
    Endogenous tissue plasminogen activator and risk of recurrent cardiac events after an acute coronary syndrome in the MIRACL study2009Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 206, nr 2, s. 551-555Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To examine the relationship of baseline tissue plasminogen activator (t-PA) to early cardiovascular risk after an acute coronary syndrome, and the effect of intensive statin therapy. Methods: We measured plasma t-PA in 2860 of the 3086 (93%) subjects in the MIRACL study, an international randomized trial of atorvastatin 80mg daily versus placebo in patients with acute coronary syndromes. The relationship of t-PA to death, non-fatal acute myocardial infarction, cardiac arrest, or worsening angina over 16 weeks was assessed by Cox Proportional Hazards. D-dimer was measured in a random sample of 395 subjects. Results: Higher baseline t-PA was significantly related to the risk of recurrent events (HR = 1.25, p = 0.0014). This relationship was unaffected by adjustment for age, sex, troponin, hsCRP, and lipids (HR = 1.17, p = 0.029), but was attenuated by adjustment including body mass index and smoking (HR = 1.14, p = 0.08). D-dimer and t-PA concentrations were not related. Atorvastatin reduced the risk of recurrent events, but did not affect t-PA or D-dimer concentrations or the relationship of t-PA to outcomes. Conclusion: In patients with acute coronary syndromes, increasing t-PA concentration was related to a higher early risk of recurrent events, paradoxically reflecting impaired endogenous fibrinolysis. This relationship is due in part to the association of t-PA with age, body mass index and smoking. Although statins lower the risk of recurrent events after acute coronary syndromes, it is unlikely that this benefit is achieved through thrombolytic and fibrinolytic pathways. Published by Elsevier Ireland Ltd.

  • 46.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Faktum kvarstår att 80 mg simvastatin dagligen ger hög myopatirisk2009Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, nr 43, s. 2783-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    [No abstract available]

  • 47.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Is high HDL cholesterol always good?2009Ingår i: ANNALS OF MEDICINE, ISSN 0785-3890, Vol. 41, nr 1, s. 11-18Artikel, forskningsöversikt (Övrigt vetenskapligt)
    Abstract [en]

    Because of the obvious negative relation between high-density lipoprotein (HDL) cholesterol and cardiovascular disease and the substantial residual risk of this disease even during treatment with high-dose statin there has been an urgent need to investigate the possible therapeutic benefit of increasing HDL. Even if treatment with nicotinic acid with its marked HDL-increasing effect has been encouraging, there is no evidence so far that specific increase of HDL cholesterol results in less cardiovascular disease. Treatment with the cholesterol ester transfer protein (CETP) inhibitor and HDL-increasing drug torcetrapib resulted in increased risk of cardiovascular disease. These negative results were followed by a lively discussion regarding the possible benefit of HDL-increasing treatment in general and CETP inhibition in particular. Suggested possible causes for the negative outcome by torcetrapib treatment are off-target non-CETP-related effect of this particular inhibitor, inability of very high blood HDL cholesterol levels to protect, induction of dysfunctional HDL, and direct atherogenic effect of CETP inhibition. It is concluded that still today little is known about the effect of specific therapeutic elevation of HDL cholesterol, particularly so through CETP inhibition on cardiovascular risk. New interventional studies on this therapeutic principle are welcomed and under way.

  • 48.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    JUPITER can yield paradigmatic shift in the prevention of cardiovascular disease. Focus on inflammation as a risk factor [JUPITER kan ge paradigmskifte i prevention av hjärt-kärlsjukdom. Fokus på inflammation som riskfaktor.]2009Ingår i: Läkartidningen, ISSN 0023-7205, Vol. 106, nr 21-22, s. 1471-1475Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    [No abstract available]

  • 49.
    Olsson, Anders G
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    JUPITER-studien lyfter fram primärprevention2009Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, nr 23, s. 1577-Artikel i tidskrift (Refereegranskat)
  • 50.
    G Olsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Lipid lowering and aortic valve disease2009Ingår i: CURRENT ATHEROSCLEROSIS REPORTS, ISSN 1523-3804, Vol. 11, nr 5, s. 377-383Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several retrospective and nonrandomized studies have indicated that lowering atherogenic lipoprotein, in particular low-density lipoprotein cholesterol, may retard the hemodynamic progression of aortic stenosis (AS). This valvular disease shares pathogenic and pathoanatomic similarities with atherosclerosis, at least in their early developments. Two randomized placebo-controlled studies researching the effect of lowering low-density lipoprotein on AS progression and its clinical consequences have been published recently-the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE) study and the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Both of these studies had neutral outcomes. The causes for the negative outcome may be that cholesterol lowering does not influence AS development in a clinically significant way or it may be due to traits in the design of the studies or treatments. Therefore, statin treatment for prevention of AS progression cannot be ruled out as a future therapeutic option in AS. The outcome of the ongoing Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) study, which is examining lipid lowering as a treatment for AS, is greatly anticipated.

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