Prior Studies
While this analysis is the first to explore the impacts of center variability on induction therapy utilization for OHT, similar topics have been explored in the renal and hepatic transplant populations. Bittermann et al (16) found that out of 69,349 liver transplants, only 27% of these patients received induction therapy and that 65.7% of the variance in induction therapy utilization was attributed to the transplant center. Dharnidharka et al (17) analyzed 166,776 kidney transplants, in which 81.8% of recipients were treated with induction therapy although the induction agent utilized was highly variable (Thymoglobulin 58% and Alemtuzumab 66%) and related to center-level characteristics.
For heart transplant recipients the clinical decision of whether to use induction therapy, in which patients to use it in, and which agents to use have been explored without accounting for center variability. A meta-analysis that included 8 randomized controlled trials (18), using various induction therapy agents, found the use of induction therapy to be protective against moderate to severe acute rejection (OR 0.7 95% CI 0.3 – 1.7). Unfortunately, the high level of heterogeneity (I2 = 77%) somewhat limits the interpretability of these results. In a separate Cochrane review (19), Penninga et alincluded 22 RCTs with 1,427 patients and demonstrated that IL‐2 receptor antagonists significantly reduced the risks of rejection (RR 0.73 95% CI 0.59 to 0.90; I2 57%) when compared to no induction therapy, although there were elevated risks of rejection in patients who received IL-2 antagonists over polyclonal antibody induction therapy (RR 2.43, 95% CI 1.01 to 5.86; I2 28%). Conversely, our study did not demonstrate substantial differences in the odds of rejection at 1-year based on the type of induction therapy utilized. While the studies included in these meta-analyses have a high degree of bias, it is still important to consider the potential different efficacies of the available induction agents. Amin et al investigated the survival of 12,103 OHT recipients from 2006 to 2015 and reported an increase in mortality associated with induction therapy, without identifying any benefits in reductions rejection rates (20). Similarly, a retrospective analysis by Whitson et al (21) of 17,857 OHT recipients from 1987 to 2012 failed to show an overall survival benefit from induction therapy. Both of these studies suggested that the benefit of induction therapy is likely seen in short-term follow-up rather and is also re-enforced by improved patient-level survival at 30- and 90-days in induction therapy recipients in our study, which was mitigated at 1-year and 5-year follow-up among the groups.