Diltiazem as a cyclosporine A-sparing agent in heart transplantation: Benefits beyond dose reduction

Medicine (Baltimore). 2022 Oct 14;101(41):e31166. doi: 10.1097/MD.0000000000031166.

Abstract

Diltiazem (DZ) is widely prescribed in transplant recipients because of its drug-drug interactions with calcineurin inhibitors (CNI). However, these interactions have been primarily investigated in renal transplantation, and data regarding the long-term efficacy and safety of DZ in orthotopic heart transplantation (OHT) are still sparse. Our study aimed to elucidate the extent to which the co-prescription of DZ reduces the dose required to maintain adequate blood levels of cyclosporine A (CsA) and the resulting effect on morbidity and mortality in OHT recipients. We performed a retrospective single-center analysis of OHT recipients on a long-term immunosuppressive regimen based on CsA and mycophenolate mofetil (MMF). The study population consisted of 95 adult OHT recipients with a mean follow-up of 15.8 ± 6.7 years. DZ was co-prescribed in 39 subjects (41.1%) and was associated with a 28.6% reduction of the mean CsA daily dose (P < .001). Patients on DZ had less frequent rejection episodes (P = .002), better renal function (P = .009) and a lower rate of end-stage renal disease (P = .008). Additionally, they developed later cardiac allograft vasculopathy (CAV). We observed no prognostic relevance of DZ co-prescription in univariate and multivariate Cox-regression analyses. In addition to reducing the CsA dose required to maintain adequate blood through levels, DZ may have nephroprotective properties in OHT. The co-administration of DZ may decelerate the development of CAV and reduce the frequency of the rejection episodes. However, the beneficial influence on morbidity has no impact on mortality.

MeSH terms

  • Adult
  • Calcineurin Inhibitors / therapeutic use
  • Cyclosporine* / therapeutic use
  • Diltiazem / therapeutic use
  • Drug Tapering
  • Graft Rejection / prevention & control
  • Heart Transplantation* / adverse effects
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Mycophenolic Acid / therapeutic use
  • Retrospective Studies

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Diltiazem
  • Mycophenolic Acid