The Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Recipients: One-Year Results of a Scandinavian Randomized Trial

Am J Transplant. 2015 Jul;15(7):1967-75. doi: 10.1111/ajt.13214. Epub 2015 Mar 17.

Abstract

Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.

Keywords: clinical research / practice; heart (allograft) function / dysfunction; heart transplantation / cardiology; immunosuppressant; mechanistic target of rapamycin: everolimus.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allografts
  • Calcineurin Inhibitors / therapeutic use*
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Everolimus / therapeutic use*
  • Female
  • Follow-Up Studies
  • Graft Rejection / diagnosis
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control*
  • Graft Survival
  • Heart Diseases / complications
  • Heart Diseases / surgery*
  • Heart Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prognosis
  • Risk Factors
  • Sirolimus / therapeutic use
  • Transplant Recipients*
  • Vascular Diseases / diagnosis
  • Vascular Diseases / drug therapy*
  • Vascular Diseases / etiology

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Sirolimus