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White, H., Gabriel, S. P., Szarek, M., Bhatt, D., Bittner, V., Diaz, R., . . . ODYSSEY, O. I. (2019). Effects of alirocumab on types of myocardial infarction: Insights from the ODYSSEY OUTCOMES trial. European Heart Journal, 40(33), 2801-2809
Öppna denna publikation i ny flik eller fönster >>Effects of alirocumab on types of myocardial infarction: Insights from the ODYSSEY OUTCOMES trial
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2019 (Engelska)Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, nr 33, s. 2801-2809Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (=1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2019
Nationell ämneskategori
Kardiologi
Identifikatorer
urn:nbn:se:liu:diva-162037 (URN)10.1093/eurheartj/ehz299 (DOI)000490154300015 ()31121022 (PubMedID)2-s2.0-85070265173 (Scopus ID)
Tillgänglig från: 2019-11-18 Skapad: 2019-11-18 Senast uppdaterad: 2020-01-09
Olsson, A. (2019). PCSK9-hämmare kan minska total dödlighet: Resultat och konsekvenser av ODYSSEY-studien. Läkartidningen, 116
Öppna denna publikation i ny flik eller fönster >>PCSK9-hämmare kan minska total dödlighet: Resultat och konsekvenser av ODYSSEY-studien
2019 (Svenska)Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116Artikel i tidskrift, Editorial material (Övrigt vetenskapligt) Published
Abstract [sv]

ODYSSEY-studien visar att subkutan injektion av 75–150 mg alirokumab var 14:e dag, som tillåter deltagare att nå LDL-kolesterol på 0,4 mmol/l, minskar risk för det primära effektmåttet kranskärlsdöd, akut hjärtinfarkt, sjukhusvård för instabil angina pectoris eller ischemisk stroke med 15 procent.

Under samma förutsättningar visar studien också att risken för total dödlighet minskar med 15 procent.

Behandlingen var säker och tolererbar under hela studien.

Abstract [en]

The ODYSSEY outcome study, including subjects with recent acute coronary syndrome on high dose statin therapy, investigated the effect of 75-150 mg alirocumab given subcutaneously every 2 weeks for 2,8 years in comparison with participants on alirocumab placebo Alirocumab decreased the risk of the primary endpoint coronary death, acute myocardial infarction, hospital admittance because of angina pectoris and ischaemic stroke by 15 percent, decreased the risk of total death by 15 percent and was safe and tolerable during the length of the study.

Ort, förlag, år, upplaga, sidor
Stockholm, Sweden: Läkartidningen förlag AB, 2019
Nationell ämneskategori
Kardiologi
Identifikatorer
urn:nbn:se:liu:diva-165426 (URN)
Tillgänglig från: 2020-05-01 Skapad: 2020-05-01 Senast uppdaterad: 2020-05-06Bibliografiskt granskad
Rosenson, R. S., Larrey, D., Waters, D. D. & Olsson, A. (2018). Comments: Praluent (Alirocumab)-Induced Renal Injury. Journal of Pharmacy Practice, 31(2), 138-139
Öppna denna publikation i ny flik eller fönster >>Comments: Praluent (Alirocumab)-Induced Renal Injury
2018 (Engelska)Ingår i: Journal of Pharmacy Practice, ISSN 0897-1900, E-ISSN 1531-1937, Vol. 31, nr 2, s. 138-139Artikel i tidskrift, Editorial material (Övrigt vetenskapligt) Published
Abstract [en]

n/a

Ort, förlag, år, upplaga, sidor
Sage Publications, 2018
Nyckelord
acute renal injury; alirocumab; rosuvastatin
Nationell ämneskategori
Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-155854 (URN)10.1177/0897190017734429 (DOI)000429881200001 ()28974137 (PubMedID)2-s2.0-85043371282 (Scopus ID)
Tillgänglig från: 2019-03-29 Skapad: 2019-03-29 Senast uppdaterad: 2019-10-24Bibliografiskt granskad
Pitts, R., Gunzburger, E., Ballantyne, C. M., Barter, P. J., Kallend, D., Leiter, L. A., . . . Schwartz, G. G. (2017). Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 6(1), Article ID e004119.
Öppna denna publikation i ny flik eller fönster >>Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure
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2017 (Engelska)Ingår 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) Published
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.

Ort, förlag, år, upplaga, sidor
WILEY-BLACKWELL, 2017
Nyckelord
acute coronary syndrome; aldosterone; morbidity/mortality
Nationell ämneskategori
Kardiologi
Identifikatorer
urn:nbn:se:liu:diva-135708 (URN)10.1161/JAHA.116.004119 (DOI)000393593300008 ()28073769 (PubMedID)
Anmärkning

Funding Agencies|F. Hoffmann-La Roche

Tillgänglig från: 2017-03-17 Skapad: 2017-03-17 Senast uppdaterad: 2018-04-16
Olsson, A., Angelin, B., Assmann, G., Binder, C. J., Bjoerkhem, I., Cedazo-Minguez, A., . . . Yvan-Charvet, L. (2017). Can LDL cholesterol be too low? Possible risks of extremely low levels. Journal of Internal Medicine, 281(6), 534-553
Öppna denna publikation i ny flik eller fönster >>Can LDL cholesterol be too low? Possible risks of extremely low levels
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2017 (Engelska)Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, nr 6, s. 534-553Artikel, forskningsöversikt (Refereegranskat) Published
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.

Ort, förlag, år, upplaga, sidor
WILEY, 2017
Nyckelord
abetalipoproteinaemia; adverse effects; hypocholesterolaemia; low-density lipoprotein; safety
Nationell ämneskategori
Annan klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-138220 (URN)10.1111/joim.12614 (DOI)000401715800001 ()28295777 (PubMedID)
Anmärkning

Funding Agencies|Foundation of Old Servants; International Task Force for The Prevention of Cardiometabolic Diseases

Tillgänglig från: 2017-06-14 Skapad: 2017-06-14 Senast uppdaterad: 2018-04-16
Schwartz, G. G., Abt, M., Bao, W., DeMicco, D., Kallend, D., Miller, M., . . . Olsson, A. (2015). Fasting Triglycerides Predict Recurrent Ischemic Events in Patients With Acute Coronary Syndrome Treated With Statins. Journal of the American College of Cardiology, 65(21), 2267-2275
Öppna denna publikation i ny flik eller fönster >>Fasting Triglycerides Predict Recurrent Ischemic Events in Patients With Acute Coronary Syndrome Treated With Statins
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2015 (Engelska)Ingår 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) Published
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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2015
Nyckelord
lipids; myocardial infarction; unstable angina
Nationell ämneskategori
Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-119573 (URN)10.1016/j.jacc.2015.03.544 (DOI)000355196300001 ()26022813 (PubMedID)
Anmärkning

Funding Agencies|F. Hoffmann-La Roche Ltd.; Pfizer; Anthera; Resverlogix; Roche; Sanofi; Amgen; AstraZeneca; Karobio; Merck

Tillgänglig från: 2015-06-23 Skapad: 2015-06-22 Senast uppdaterad: 2017-12-04
Raal, F. J., Stein, E. A., Dufour, R., Turner, T., Civeira, F., Burgess, L., . . . Gaudet, D. (2015). PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. The Lancet, 385(9965), 331-340
Öppna denna publikation i ny flik eller fönster >>PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial
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2015 (Engelska)Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, nr 9965, s. 331-340Artikel i tidskrift (Refereegranskat) Published
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.

Ort, förlag, år, upplaga, sidor
Elsevier: Lancet, 2015
Nationell ämneskategori
Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-114580 (URN)10.1016/S0140-6736(14)61399-4 (DOI)000348509000026 ()
Tillgänglig från: 2015-02-27 Skapad: 2015-02-26 Senast uppdaterad: 2017-12-04
Angelin, B., Kristensen, J. D., Eriksson, M., Carlsson, B., Klein, I., Olsson, A., . . . Ladenson, P. W. (2015). 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 eprotirome. Journal of Internal Medicine, 277(3), 331-342
Öppna denna publikation i ny flik eller fönster >>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 eprotirome
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2015 (Engelska)Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, nr 3, s. 331-342Artikel i tidskrift (Refereegranskat) Published
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.

Ort, förlag, år, upplaga, sidor
Wiley: 12 months, 2015
Nyckelord
cholesterol; hypercholesterolaemia; lipoprotein; liver; thyroid
Nationell ämneskategori
Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-116513 (URN)10.1111/joim.12261 (DOI)000349977300005 ()24754313 (PubMedID)
Anmärkning

Funding Agencies|Karo Bio

Tillgänglig från: 2015-03-27 Skapad: 2015-03-27 Senast uppdaterad: 2017-12-04
Sjouke, B., Langslet, G., Ceska, R., Nicholls, S. J., Nissen, S. E., Ohlander, M., . . . Kastelein, J. J. P. (2014). Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a randomised, double-blind, placebo-controlled phase 3 study. LANCET DIABETES and ENDOCRINOLOGY, 2(6), 455-463
Öppna denna publikation i ny flik eller fönster >>Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a randomised, double-blind, placebo-controlled phase 3 study
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2014 (Engelska)Ingår i: LANCET DIABETES and ENDOCRINOLOGY, ISSN 2213-8587, Vol. 2, nr 6, s. 455-463Artikel i tidskrift (Refereegranskat) Published
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.

Ort, förlag, år, upplaga, sidor
Elsevier: Lancet, 2014
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-108164 (URN)10.1016/S2213-8587(14)70006-3 (DOI)000336724300022 ()
Tillgänglig från: 2014-06-26 Skapad: 2014-06-26 Senast uppdaterad: 2014-06-26
Olsson, A. G. (2014). [Guidelines for cholesterol treatment--the obstacle remains in Stockholm]. [Letter to the editor]. Läkartidningen, 111(20), 885
Öppna denna publikation i ny flik eller fönster >>[Guidelines for cholesterol treatment--the obstacle remains in Stockholm].
2014 (Svenska)Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 20, s. 885-Artikel i tidskrift, Letter (Övrigt vetenskapligt) Published
Nationell ämneskategori
Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-116860 (URN)24908807 (PubMedID)
Tillgänglig från: 2015-04-08 Skapad: 2015-04-08 Senast uppdaterad: 2017-12-04
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