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.