Is a Switch to Cyclosporine from Tacrolimus a Risk in Heart Transplant Recipients

Purpose Cyclosporine (CsA) became available in the US in 1983 and improved clinical outcomes. Another calcineurin inhibitor, tacrolimus (TAC), became available in the 1990s and demonstrated benefit in further reducing rejection. In most heart transplant (HTx) programs, TAC is currently the drug of choice for immunosuppression. However, a switch to CsA does occur due to adverse effects from TAC. It is not well-established that this switch to CSA results in subsequent non-inferior outcomes. Therefore, we reviewed our single center experience to assess for real world potential outcomes. Methods Between 2010 and 2017, we identified 58 HTx patients who were administered CsA in place of TAC mostly due to neurologic adverse effects from TAC. For comparison, a TAC group was matched based on age, sex, baseline renal function and time from transplant. The average time of this switch occurred at 6.6 ± 1.1 months post-transplant. Outcomes included subsequent 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR) and 3-year subsequent survival, freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), and freedom non-fatal major adverse cardiac event (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke). Results The CsA/MMF group compared to the TAC/MMF group had significantly lower subsequent 3-year survival and worse renal function at 1-year (after the switch to CsA). There was similar subsequent 3-year freedom from CAV and NF-MACE and 1-year rejections between the two groups. (see table) Conclusion In the current era in a large, single center study there are indications that a switch to CsA from TAC may be inferior in heart transplant recipients. Further investigation with larger numbers is needed to confirm these findings.