دورية أكاديمية
Everolimus for the Prevention of Calcineurin-Inhibitor-Induced Left Ventricular Hypertrophy After Heart Transplantation (RADTAC Study).
| العنوان: | Everolimus for the Prevention of Calcineurin-Inhibitor-Induced Left Ventricular Hypertrophy After Heart Transplantation (RADTAC Study). |
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| المؤلفون: | Anthony C; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia., Imran M; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia., Pouliopoulos J; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute., Emmanuel S; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia., Iliff JW; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia., Moffat KJ; Medical Imaging Department, St. Vincent's Hospital, Sydney, Australia., Ross J; Medical Imaging Department, St. Vincent's Hospital, Sydney, Australia., Graham RM; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Kotlyar E; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Muthiah K; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Keogh AM; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Hayward CS; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Macdonald P; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Jabbour A; Heart and Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia. Electronic address: Andrew.Jabbour@svha.org.au. |
| المصدر: | JACC. Heart failure [JACC Heart Fail] 2021 Apr; Vol. 9 (4), pp. 301-313. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 101598241 Publication Model: Print Cited Medium: Internet ISSN: 2213-1787 (Electronic) Linking ISSN: 22131779 NLM ISO Abbreviation: JACC Heart Fail Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Elsevier, [2013]- |
| مواضيع طبية MeSH: | Heart Failure* , Heart Transplantation*, Calcineurin ; Calcineurin Inhibitors/adverse effects ; Drug Therapy, Combination ; Everolimus ; Graft Rejection/prevention & control ; Graft Survival ; Humans ; Hypertrophy, Left Ventricular/prevention & control ; Immunosuppressive Agents ; Prospective Studies |
| مستخلص: | Objectives: This study aimed to determine the safety and efficacy of combined low-dose everolimus and low-dose tacrolimus compared with standard-dose tacrolimus in attenuating left ventricular hypertrophy (LVH) after orthotopic heart transplantation (OHT). Background: Calcineurin inhibitors (CNIs) such as tactrolimus are important in preventing cardiac allograft rejection and reducing mortality after OHT. However CNIs are causatively linked to the development of LVH, and are associated with nephrotoxicity and vasculopathy. CNI-sparing agents such as everolimus have been hypothesized to inhibit adverse effects of CNIs. Methods: In this prospective, randomized, open-label study, OHT recipients were randomized at 12 weeks after OHT to a combination of low-dose everolimus and tacrolimus (the RADTAC group) or standard-dose tacrolimus (the TAC group), with both groups coadministered mycophenolate and prednisolone. The primary endpoint was LVH indexed as the change in left ventricular mass (ΔLVM) by cardiovascular magnetic resonance (CMR) imaging from 12 to 52 weeks. Secondary endpoints included CMR-based myocardial performance, T1 fibrosis mapping, blood pressure, and renal function. Safety endpoints included episodes of allograft rejection and infection. Results: Forty stable OHT recipients were randomized. Recipients in the RADTAC group had significantly lower tacrolimus levels compared with the TAC group (6.5 ± 3.5 μg/l vs. 8.6 ± 2.8 μg/l; p = 0.02). The mean everolimus level in the RADTAC group was 4.2 ± 1.7 μg/l. A significant reduction in LVM was observed in the RADTAC group compared with an increase in LVM in the TAC group (ΔLVM = -13.0 ± 16.8 g vs. 2.1 ± 8.4 g; p < 0.001). Significant differences were also noted in secondary endpoints measuring function and fibrosis (Δ circumferential strain = -2.9 ± 2.8 vs. 2.1 ± 2.3; p < 0.001; ΔT1 mapping values = -32.7 ± 51.3 ms vs. 26.3 ± 90.4 ms; p = 0.003). No significant differences were observed in blood pressure (Δ mean arterial pressure = 4.2 ± 18.8 mm Hg vs. 2.8 ± 13.8 mm Hg; p = 0.77), renal function (Δ creatinine = 3.1 ± 19.9 μmol/l vs. 9 ± 21.8 μmol/l; p = 0.31), frequency of rejection episodes (p = 0.69), or frequency of infections (p = 0.67) between groups. Conclusions: The combination of low-dose everolimus and tacrolimus compared with standard-dose tacrolimus safely attenuates LVH in the first year after cardiac transplantation with an observed reduction in CMR-measured fibrosis and an improvement in myocardial strain. Competing Interests: Funding Support and Author Disclosures This study was funded by an unrestricted grant from Novartis and The St. Vincent’s Clinic Foundation, Australia. Dr. Keogh has conducted clinical trial research for Actelion, Pfizer, United Therapeutics, Arena, Acceleron, Bayer, Respira, GlaxoSmithKline, and Gilead. Dr. Macdonald has received an institutional research grant from Novartis; has been on the advisory boards of Novartis and AstraZeneca; has received speaker honoraria from Servier; and has received travel support from Transmedics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Copyright © 2021 American College of Cardiology Foundation. All rights reserved.) |
| التعليقات: | Comment in: JACC Heart Fail. 2021 Apr;9(4):314-316. (PMID: 33795117) |
| فهرسة مساهمة: | Keywords: calcineurin inhibition; cardiac transplantation; everolimus; fibrosis; hypertrophy; immunosuppression; remodeling; tacrolimus |
| المشرفين على المادة: | 0 (Calcineurin Inhibitors) 0 (Immunosuppressive Agents) 9HW64Q8G6G (Everolimus) EC 3.1.3.16 (Calcineurin) |
| تواريخ الأحداث: | Date Created: 20210402 Date Completed: 20211025 Latest Revision: 20220531 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.jchf.2021.01.007 |
| PMID: | 33795116 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2213-1787 |
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| DOI: | 10.1016/j.jchf.2021.01.007 |