Induction Therapy in Patients with Prolonged Ischemic Times May Be Protective for Early Graft Failure

PURPOSE: Primary graft dysfunction (PGD) in heart transplantation (HTx) patients is the leading cause of death within the first 30 days of HTx. Ischemic time >4 hours has been associated with a significant increase in mortality at 30 days post-transplant and up to 6 years post-transplant. The optimal immunosuppression regimen including induction therapy to prevent allograft failure is unclear. Induction therapy may have a protective effect against ischemia-reperfusion injury, a main mechanism of allograft injury after HTx. We sought to evaluate the effect of induction therapy in heart transplant recipients with longer ischemic times in both early and long-term graft failure. METHODS: This retrospective cohort study used the United Network for Organ Sharing (UNOS) and included adult (>21yr) heart transplant patients from Jun 30, 2004 to Mar 2015. The effect of induction therapy, either basiliximab (IL-2Rab) or ATG/ALG/thymoglobulin, on all-cause early and late graft failure was estimated by a logistic regression adjusted for the covariates ischemic time, age, African American race, serum creatinine >2.5, HLA mismatch > 4, and acute rejection episodes. The Inverse Probability Treatment Weighting (IPTW) was used to control for imbalanced propensity of receiving induction given the covariates. RESULTS: At 30 days, induction was shown to reduce graft failure OR 0.69 (95% CI, 0.57-0.82) in all comers with no additional benefit for patients with prolonged ischemic time OR 1.08 (95% CI 0.87-1.36). Induction had no effect on long term graft failure up to 5.6 years OR 0.96 (95% CI 0.88 -1.04), except in patients with prolonged ischemic time OR 0.88 (95%CI 0.79-0.98). CONCLUSION: Our results suggest that induction therapy may be protective against graft failure at 30 days, and late graft failure up to five years in a subset of patients with prolonged ischemic times.