Are Calcineurin Inhibitor-Free Protocols Safe and Effective in the Long-Term After Heart Transplant?

Calcineurin inhibitors (CNIs) tacrolimus and cyclosporine, have improved outcomes of heart transplant (HTx) patients but unfortunately have many side effects which include nephrotoxicity, hypertension, and malignancy. CNI-free regimens may protect the kidneys but at the risk of rejection. The purpose of this study was to assess our center's experience with CNI minimization and discontinuation. We assessed 34 HTx patients transplanted between 2010-2020, who transitioned to CNI-free regimens 6m-2 years post HTx and 2-5 years post HTx. Outcomes assessed were any treated rejection (ATR; including acute cellular rejection [ACR], antibody-mediated rejection [AMR], and biopsy-negative rejection [BNR]), survival, cardiac dysfunction (ejection fraction ≤40%) in the 1 year following CNI-free initiation. We also assessed the need for antihypertensive medications, HgbA1c, and estimated glomerular filtration rate (eGFR). Of 34 HTx recipients, 89% of patients were successfully weaned off CNI at <2 years and 94% at 2-5 years after transplant. eGFR for both groups was markedly improved at 1-year post CNI-free initiation. There was no difference between groups in anti-hypertensive medications or HgbA1c. However, CNI had to be restarted in 50% of the CNI-free in <2 years group and in 31% of the CNI-free at 2-5 years group. Return to CNI was for: rejection, medication intolerance, and death. (Table). CNI-free regimens are safe and efficacious for select patients but may not be sustainable. Additional strategies for renal protection and immunosuppression optimization are warranted. [ABSTRACT FROM AUTHOR]