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Jansson, Kjell
Publications (10 of 23) Show all publications
Rådegran, G., Kjellström, B., Ekmehag, B., Larsen, F., Rundqvist, B., Berg Blomquist, S., . . . Söderberg, S. (2016). Characteristics and survival of adult Swedish PAH and CTEPH patients 2000-2014. Scandinavian Cardiovascular Journal, 50(4), 243-250
Open this publication in new window or tab >>Characteristics and survival of adult Swedish PAH and CTEPH patients 2000-2014
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2016 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 50, no 4, p. 243-250Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: The Swedish Pulmonary Arterial Hypertension Register (SPAHR) is an open continuous register, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients from 2000 and onwards. We hereby launch the first data from SPAHR, defining baseline characteristics and survival of Swedish PAH and CTEPH patients.

DESIGN: Incident PAH and CTEPH patients 2008-2014 from all seven Swedish PAH-centres were specifically reviewed.

RESULTS: There were 457 PAH (median age: 67 years, 64% female) and 183 CTEPH (median age: 70 years, 50% female) patients, whereof 77 and 81%, respectively, were in functional class III-IV at diagnosis. Systemic hypertension, diabetes, ischaemic heart disease and atrial fibrillation were common comorbidities, particularly in those >65 years. One-, 3- and 5-year survival was 85%, 71% and 59% for PAH patients. Corresponding numbers for CTEPH patients with versus without pulmonary endarterectomy were 96%, 89% and 86% versus 91%, 75% and 69%, respectively. In 2014, the incidence of IPAH/HPAH, associated PAH and CTEPH was 5, 3 and 2 per million inhabitants and year, and the prevalence was 25, 24 and 19 per million inhabitants.

CONCLUSION: The majority of the PAH and CTEPH patients were diagnosed at age >65 years, in functional class III-IV, and exhibiting several comorbidities. PAH survival in SPAHR was similar to other registers.

Place, publisher, year, edition, pages
Taylor & Francis, 2016
Keywords
Incident, prevalent, pulmonary hypertension, survival
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-130206 (URN)10.1080/14017431.2016.1185532 (DOI)000379819900008 ()27146648 (PubMedID)
Note

Funding agencies:  Actelion Pharmaceuticals Sweden AB; Bayer Health Care; Eli Lilly Sweden; Glaxo-SmithKline; Nordicinfu Care; Pfizer; SALAR (SKL); "ALF" foundations

Available from: 2016-07-14 Created: 2016-07-14 Last updated: 2018-03-20Bibliographically approved
Andreassen, A. K., Andersson, B., Gustafsson, F., Eiskjaer, H., Radegran, G., Gude, E., . . . Gullestad, L. (2016). Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study. American Journal of Transplantation, 16(4), 1238-1247
Open this publication in new window or tab >>Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study
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2016 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 16, no 4, p. 1238-1247Article in journal (Refereed) Published
Abstract [en]

In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4mL/min (standard deviation [SD] 20.2mL/min) versus 59.2mL/min (SD 17.4mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3mL/min (95% CI 11.1-25.6mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade 2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p=0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage. A follow-up study of the SCHEDULE trial, which randomized de novo heart transplant recipients to everolimus with cyclosporine discontinuation or to standard-exposure cyclosporine, shows that measured glomerular filtration rate remains significantly higher in the everolimus group at three years posttransplant, with significantly reduced progression of allograft vasculopathy compared to cyclosporine therapy.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
Keywords
clinical research; practice; heart transplantation; cardiology; immunosuppression; immune; immunosuppressant; mechanistic target of rapamycin: everolimus; immunosuppressant; mechanistic target of rapamycin (mTOR); clinical trial modulation
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127413 (URN)10.1111/ajt.13588 (DOI)000373075400024 ()26820618 (PubMedID)
Available from: 2016-05-02 Created: 2016-04-26 Last updated: 2017-05-03
Gullestad, L., Eiskjaer, H., Gustafsson, F., Riise, G. C., Karason, K., Dellgren, G., . . . Iversen, M. (2016). Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial. Transplant International, 29(7), 819-829
Open this publication in new window or tab >>Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial
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2016 (English)In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 29, no 7, p. 819-829Article in journal (Refereed) Published
Abstract [en]

The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2016
Keywords
calcineurin inhibitor, certican, cyclosporine, everolimus, heart, lung, randomized, renal impairment, tacrolimus, transplantation
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-130205 (URN)10.1111/tri.12783 (DOI)000379691200009 ()27067532 (PubMedID)
Note

Funding agencies: Novartis Scandinavia

Available from: 2016-07-14 Created: 2016-07-14 Last updated: 2017-11-28Bibliographically approved
Andreassen, A., Andersson, B., Gustafsson, F., Eiskjaer, H., Rdegran, G., Gude, E., . . . Gullestad, L. (2014). Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial. American Journal of Transplantation, 14(8), 1828-1838
Open this publication in new window or tab >>Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial
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2014 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 14, no 8, p. 1828-1838Article in journal (Refereed) Published
Abstract [en]

In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3-6 ng/mL) with reduced-exposure cyclosporine (n 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7-11 weeks and everolimus exposure increased (6-10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean +/- SD: 79.8 +/- 17.7 mL/min/1.73m 2 vs. 61.5 +/- 19.6 mL/min/1.73m 2; pless than0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7-11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, pless than0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.

Place, publisher, year, edition, pages
Wiley, 2014
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-109582 (URN)10.1111/ajt.12809 (DOI)000339433100018 ()25041227 (PubMedID)
Available from: 2014-08-21 Created: 2014-08-21 Last updated: 2017-12-05
Arbring, K., Chaireti, R., Janzon, M., Uppugunduri, S., Jansson, K. & Lindahl, T. (2013). First experience of structured introduction of new oral anticoagulants in a Swedish health care district: dabigatran as an alternative to warfarin in atrial fibrillation. In: : . Paper presented at XXIVth Congress of the International Society of Thrombosis and Haemostasi (ISTH 2013), 29 June - 4 Juli 2013, Amsterdam, Holland.
Open this publication in new window or tab >>First experience of structured introduction of new oral anticoagulants in a Swedish health care district: dabigatran as an alternative to warfarin in atrial fibrillation
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2013 (English)Conference paper, Published paper (Refereed)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103424 (URN)
Conference
XXIVth Congress of the International Society of Thrombosis and Haemostasi (ISTH 2013), 29 June - 4 Juli 2013, Amsterdam, Holland
Available from: 2014-01-20 Created: 2014-01-20 Last updated: 2014-08-26
Arora, S., Gude, E., Aage Mortensen, S., Eiskjaer, H., Riise, G., Mared, L., . . . Gullestad, L. (2012). Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate. The Journal of Heart and Lung Transplantation, 31(3), 259-265
Open this publication in new window or tab >>Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate
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2012 (English)In: The Journal of Heart and Lung Transplantation, ISSN 1053-2498, E-ISSN 1557-3117, Vol. 31, no 3, p. 259-265Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (FIX) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. less thanbrgreater than less thanbrgreater thanMETHODS: This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediarninetetraacetic acid clearance. less thanbrgreater than less thanbrgreater thanRESULTS: In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((Delta mGFR 6.7 +/- 9.0 vs -1.6 +/- 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (Delta mGFR 5.1 +/- 11.1 vs -0.5 +/- 8.7 ml/min/1.73 m(2); p andlt; 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CM reduction during the study period. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
thoracic transplantation, heart and lung transplantation, everolimus, CNI reduction, renal failure, GFR improvement
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-75892 (URN)10.1016/j.healun.2011.12.010 (DOI)000300806500006 ()
Note
Funding Agencies|Novartis Scandinavia||Available from: 2012-03-16 Created: 2012-03-16 Last updated: 2017-12-07
Selimovic, N., Lovgren Ekmehag, B., Jansson, K., Larsen, F., Soderberg, S. & Wikstrom, G. (2012). Pulmonary Arterial Hypertension in Sweden: First Data from a National Registry in JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol 31, issue 4, pp S284-S284. In: JOURNAL OF HEART AND LUNG TRANSPLANTATION (pp. S284-S284). Elsevier, 31(4)
Open this publication in new window or tab >>Pulmonary Arterial Hypertension in Sweden: First Data from a National Registry in JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol 31, issue 4, pp S284-S284
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2012 (English)In: JOURNAL OF HEART AND LUNG TRANSPLANTATION, Elsevier , 2012, Vol. 31, no 4, p. S284-S284Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76950 (URN)000302207900835 ()
Available from: 2012-05-02 Created: 2012-04-27 Last updated: 2012-05-02
Arora, S., Erikstad, I., Ueland, T., Sigurdardottir, V., Ekmehag, B., Jansson, K., . . . Gullestad, L. (2012). Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus—Results of a Multicenter Trial. American Journal of Transplantation, 12(10), 2700-2709
Open this publication in new window or tab >>Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus—Results of a Multicenter Trial
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2012 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 12, no 10, p. 2700-2709Article in journal (Refereed) Published
Abstract [en]

In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 +/- 3.8% and 1.6 +/- 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 +/- 4.0 vs. 0.3 +/- 3.1%; p = 0.02) and necrotic component (6.5 +/- 8.5 vs. 1.1 +/- 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx andgt;5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2012
Keywords
Cardiac allograft vasculopathy, everolimus, inflammation, virtual histology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85087 (URN)10.1111/j.1600-6143.2012.04234.x (DOI)000309180000017 ()
Note

Funding Agencies|Novartis Scandinavia||

Available from: 2012-11-02 Created: 2012-11-02 Last updated: 2017-12-07
Arora, S., Erikstad, I., Wennerblom, B., Sigurdardottir, V., Eiskjaer, H., Botker, H., . . . Gullestad, L. (2011). Effect of Everolimus Introduction and Calcineurin Inhibitor Reduction on Cardiac Allograft Vasculopathy Assessed by Virtual Histology in JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol 30, issue 4, pp S33-S34. In: JOURNAL OF HEART AND LUNG TRANSPLANTATION (pp. S33-S34). ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA, 30(4)
Open this publication in new window or tab >>Effect of Everolimus Introduction and Calcineurin Inhibitor Reduction on Cardiac Allograft Vasculopathy Assessed by Virtual Histology in JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol 30, issue 4, pp S33-S34
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2011 (English)In: JOURNAL OF HEART AND LUNG TRANSPLANTATION, ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA , 2011, Vol. 30, no 4, p. S33-S34Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67715 (URN)000288924300078 ()
Available from: 2011-04-26 Created: 2011-04-26 Last updated: 2011-05-09
Arora, S., Ueland, T., Wennerblom, B., Sigurdadottir, V., Eiskjaer, H., E. Botker, H., . . . Gullestad, L. (2011). Effect of Everolimus Introduction on Cardiac Allograft Vasculopathy-Results of a Randomized, Multicenter Trial. Transplantation, 92(2), 235-243
Open this publication in new window or tab >>Effect of Everolimus Introduction on Cardiac Allograft Vasculopathy-Results of a Randomized, Multicenter Trial
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2011 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 92, no 2, p. 235-243Article in journal (Refereed) Published
Abstract [en]

Background. Everolimus reduces the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown. Methods. In this Nordic Certican Trial in Heart and lung Transplantation substudy, 111 maintenance HTx recipients (time post-HTx 5.8 +/- 4.3 years) randomized to everolimus+reduced calcineurin inhibitor (CNI) or standard CNI had matching (intravascular ultrasound) examinations at baseline and 12 months allowing accurate assessment of CAV progression. Results. No significant difference in CAV progression was evident between the treatment groups (P=0.30). When considering patients receiving concomitant azathioprine (AZA) therapy (n=39), CAV progression was attenuated with everolimus versus standard CNI (Delta maximal intimal thickness 0.00 +/- 0.04 and 0.04 +/- 0.04 mm, Delta percent atheroma volume 0.2%+/- 3.0% and 2.6%+/- 2.5%, and Delta total atheroma volume 0.25 +/- 14.1 and 19.8 +/- 20.4 mm(3), respectively [Pless than0.05]). When considering patients receiving mycophenolate mofetil (MMF), accelerated CAV progression occurred with everolimus versus standard CNI (Delta maximal intimal thickness 0.06 +/- 0.12 vs. 0.02 +/- 0.06 mm and Delta percent atheroma volume 4.0%+/- 6.3% vs. 1.4%+/- 3.1%, respectively; Pless than0.05). The levels of C-reactive protein and vascular cell adhesion molecule-1 declined significantly with AZA+everolimus, whereas MMF+everolimus patients demonstrated a significant increase in levels of C-reactive protein, vascular cell adhesion molecule-1, and von Willebrand factor. Conclusions. Conversion to everolimus and reduced CNI does not influence CAV progression among maintenance HTx recipients. However, background immunosuppressive therapy is important as AZA+everolimus patients demonstrated attenuated CAV progression and a decline in inflammatory markers, whereas the opposite pattern was seen with everolimus +MMF. The different effect of everolimus when combined with AZA versus MMF could potentially reflect hitherto unknown interactions.

Place, publisher, year, edition, pages
Williams and Wilkins, 2011
Keywords
Cardiac allograft vasculopathy; Intravascular ultrasound; Everolimus
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69792 (URN)10.1097/TP.0b013e31822057f1 (DOI)000292633000023 ()
Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08
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