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The utility of immunosuppressive induction therapy (IT) following heart transplantation remains contested. In order to evaluate the effectiveness and safety of IT, we conducted a systematic review and network meta-analysis (NMA), evaluating outcomes at 1 year post-heart transplantation. We searched bibliographic databases for studies published from January 2000 to July 2021, reporting on the impact of any IT agent in adult patients undergoing heart transplantation. We performed a frequentist NMA evaluating the impact of currently available agents on 1-year all-cause mortality and treated rejection. The analysis generated direct and/or indirect estimates on the effect of IT on outcomes as relative risks (RR). The GRADE framework informed the quality of evidence. Of the 3,913 publications identified, 23 full-text studies proved eligible, of which 10 reported mortality or rejection outcomes at 1-year, informing the comparison among basiliximab, thymoglobulin (ATG), and no IT. These studies included 7 randomized controlled trials (RCTs) and 3 observational studies with adjusted analyses. Compared to no IT, ATG (RR 0.87, 95% CI 0.80-0.94) was associated with a significantly decreased risk of rejection, while basiliximab was not (RR 1.02, 95% CI 0.89-1.16). Mortality at 1 year was similar with vs without IT - ATG: RR 4.82, 95% CI 0.63-36.71 and basiliximab: RR 4.26, 95% CI 0.57-32.02. The use of ATG was associated with a significantly lower risk of rejection compared to basiliximab (RR 0.85, 95% CI 0.77-0.94), but with similar mortality (RR 1.14, 95% CI 0.40-3.23). As compared to the full network, our sensitivity analysis of RCTs alone showed no significant differences in pooled estimates of rejection or mortality for any of the network comparisons. With low certainty in the synthetized evidence, this NMA suggests that the use of IT does not confer mortality benefit at 1 year after heart transplantation. The risk of rejection may, however, be reduced by ATG compared to no IT or basiliximab, although this was not statistically significant when only evaluating data from RCTs, likely due to the small number of events and insufficient power. The utility of IT in specific patient populations, in the long-term, and on other outcomes such as infections, graft dysfunction, kidney dysfunction, and malignancies, remains to be explored. [ABSTRACT FROM AUTHOR]

In patients undergoing heart transplantation (HTx), induction therapy (IT) provides early intense immunosuppression. Whether to use IT, and the choice of optimal regimen remains controversial. We undertook a systematic review and network meta-analysis to assess outcomes following the use of IT agents, that informed a clinical practice guideline on the utility of contemporary agents: Thymoglobulin and Basiliximab. We recruited an international, multidisciplinary panel, inclusive of 3 patient partners, 5 cardiologists, 1 surgeon, 1 nurse practitioner, 1 pharmacist, and 4 methodologists. We used the GRADE framework summarize findings and develop recommendations. To develop internationally applicable recommendations, our panel took a global perspective. The panel considered balance between benefits and harms, quality of evidence, and patient's values and preferences, to make recommendations for or against the use of Thymoglobulin or Basiliximab. The panel focused on the following outcomes: all-cause mortality, cellular rejection (requiring treatment), infection, renal dysfunction, and malignancy. The review provided low- or, in most cases, very low-quality evidence of either benefit or harm of the two agents, leaving the effects of the interventions uncertain. The panel judged that with low or very low-quality evidence providing no compelling suggestion of benefit, the majority of patients would be reluctant to receive an intervention with possible serious adverse effects. Therefore, our review resulted in weak recommendations as follows: Recommendation #1: In adult HTx recipients, we suggest against the routine use of Basiliximab, as compared to no induction therapy. Recommendation #2: In adult HTx recipients, we suggest against the routine use of Thymoglobulin, as compared to no induction therapy. Recommendation #3: In adult HTx recipients for whom induction therapy is deemed desirable, we suggest using Thymoglobulin over Basiliximab. Our panel made weak recommendations against the routine use of IT agents. In select patients in whom shared decision-making leads to a decision to choose IT, the panel favored the use of Thymoglobulin over Basiliximab. Additional studies are needed to identify patient subgroups that may derive benefit from IT. [ABSTRACT FROM AUTHOR]