Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation

Clin Transplant. 2013 Nov-Dec;27(6):E649-58. doi: 10.1111/ctr.12241. Epub 2013 Sep 12.

Abstract

We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long-term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient-years) was significantly higher than that observed on CNI therapy in the pre-conversion period (2.2 per 100 patient-years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post-conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow-up. Conversion to a CNI-free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post-conversion rejection could help to refine the current PSI conversion strategies.

Keywords: cardiac transplantation; complications; everolimus; rejection; sirolimus.

Publication types

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

MeSH terms

  • Aged
  • Calcineurin Inhibitors*
  • Cell Proliferation / drug effects
  • Everolimus
  • Female
  • Follow-Up Studies
  • Graft Rejection / etiology*
  • Graft Survival
  • Heart Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • Spain / epidemiology
  • Survival Rate

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus
  • Sirolimus