Rapid Corticosteroid Withdrawal After Cardiac Transplantation Improves Outcomes

Modern immunosuppressive regimens have been associated with lower rejection rates after heart transplantation (HTx), yet long-term outcomes have remained limited by drug-related complications. Since 2010, our program has implemented a protocolized corticosteroid withdrawal (CSW) strategy following induction with rabbit anti-thymocyte globulin (RATG) and methylprednisolone. The protocol consists of shifting from a high-dose regimen to a minimization approach with a goal of steroid discontinuation within 12 months.

We evaluated the impact of this approach on the combined primary endpoint of freedom from allograft rejection ISHLT ≥ 2R, infection, non-cutaneous cancer, or coronary artery vasculopathy (CAV). We conducted a retrospective single-center study including 418 HTx patients. Patients were divided according to era of HTx: Early (1983-1998); Recent (1999-02/2010), and Corticosteroid withdrawal (CSW) (03/2010-06/2018). Multivariate Cox analyses identified predictors of adverse outcomes.

Five-year corticosteroid use markedly decreased over eras (Early 61, 4%, Recent 20, 3%, CSW 3, 4% at 5 years; p < 0.001). Freedom from the composite primary endpoint significantly improved with CSW (Early: HR: 3.42; 95% CI: 2.49-4.68; Recent: HR: 2.9; 95% CI: 4.1, both p < 0.0001 compared to CSW.) Only prednisone dose (HR:1.19; 95% CI: 1.09-1.30; p < 0.0001) and era of transplantation (Early vs. CSW: HR:2.70; 95% CI: 1.91-3.81; p < 0.0001; Recent vs. CSW: HR:2.38; 95% CI: 1.68-3.39; p < 0.0001) were independently associated with worse outcomes in the final multivariate Cox model. Notably, death, rejection, infection, and CAV were less frequent in the CSW era.

Protocolized CSW within 1 year after HTx was associated with improved long-term outcomes, including death, fewer rejection episodes, infections, and CAV. These findings support rapid steroid tapering as a safe and effective strategy in contemporary HTx.