Quadritherapy vs standard tritherapy immunosuppressant regimen after heart transplantation: A propensity score-matched cohort analysis

Am J Transplant. 2020 Oct;20(10):2791-2801. doi: 10.1111/ajt.15849. Epub 2020 Apr 17.

Abstract

After heart transplant, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting calcineurin inhibitors (CNIs) into EVL. The aim of this study was to describe the effects of combining low-dose EVL and CNIs in maintenance immunosuppression regimen (quadritherapy) and compare it with standard tritherapy associating standard-dose CNIs, mycophenolate mofetil, and corticosteroids. In the 3-year registry cohort of heart transplanted patients, those who received quadritherapy were compared with those who received tritherapy. EVL was added after 3 months posttransplant. Three analyses were performed to control for confounders: propensity score matching, multivariable survival, and inverse probability score weighting analyses. Among 213 patients who were included (75 with quadritherapy), propensity score matching selected 64 unique pairs of patients with similar characteristics. In the matched cohort (n = 128), quadritherapy was associated with fewer deaths (3 [4.7%] vs 17 [21.9%], P = .007) and biopsy-proven acute rejections (15 [23.4%] vs 31 [48.4%], P = .002). These results were confirmed in the overall cohort (n = 213), after multivariable and inverse probability score weighting analyses. Renal function and donor-specific HLA-antibodies remained similar in both groups. Low-dose combination quadritherapy was associated with fewer deaths and rejections, compared with standard immunosuppression tritherapy.

Keywords: clinical research/practice; heart (allograft) function/dysfunction; heart transplantation/cardiology; immunosuppressant-mechanistic target of rapamycin: everolimus; immunosuppression/immune modulation; immunosuppressive regimens-maintenance; rejection: acute.

MeSH terms

  • Cohort Studies
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control
  • Heart Transplantation*
  • Humans
  • Immunosuppressive Agents* / therapeutic use
  • Mycophenolic Acid / therapeutic use
  • Propensity Score

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid