Sirolimus-based immunosuppression and reported rejection or death in heart transplant recipients using the U.S. Food and Drug Administration Adverse Event Reporting System.

BACKGROUND

Sirolimus, although not approved for heart transplant recipients (HTRs), is frequently prescribed off-label for mitigating calcineurin inhibitor-related toxicity and promoting graft survival. However, its adverse event profile and real-world outcome associations within specific immunosuppressive combinations remain unclear.

METHODS

This retrospective pharmacovigilance study utilized data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). To minimize confounding by concomitant medication, paired comparisons were restricted to regimens differing only by sirolimus use. Reporting odds ratios (RORs) and adjusted RORs (aRORs), controlling for demographic and geographic variables, were calculated for the composite outcome of transplant rejection or death. Each sirolimus-containing regimen was compared with its corresponding nonsirolimus reference.

RESULTS

The sirolimus plus tacrolimus regimen showed lower disproportional reporting of transplant rejection or death than the tacrolimus regimen (ROR, 0.532 [95% CI, 0.284-0.994], P=0.048; aROR, 0.419 [95% CI, 0.218-0.804], P=0.009). In other tacrolimus-based regimens (tacrolimus plus mycophenolic acid, tacrolimus plus prednisone, and tacrolimus plus mycophenolic acid plus prednisone), sirolimus addition consistently showed RORs and aRORs <1.000, indicating a similar but nonsignificant trend toward lower reporting of transplant rejection or death.

CONCLUSIONS

This FAERS-based analysis suggested an association between sirolimus-containing regimens and lower disproportional reporting of transplant rejection or death among HTRs. These findings should be interpreted as hypothesis-generating, as spontaneous reporting data are susceptible to confounding and cannot establish causality. Prospective studies with detailed clinical data are needed to determine whether this association persists after adequate confounding control.