Abstract 4369405: Comparative Cardiac Safety of Bruton Tyrosine Kinase Inhibitors: A Bayesian Network Meta-Analysis

Background: Bruton tyrosine kinase inhibitors (BTKi) are essential in managing B-cell malignancies, but cardiac toxicity remains a major concern. Ibrutinib, the first-in-class agent, has been linked to many cardiac adverse events, prompting investigation of newer BTKis such as acalabrutinib and zanubrutinib. We performed a Bayesian network meta-analysis to assess the comparative cardiac safety of these agents. Methods: We systematically searched PubMed, Embase, and the Cochrane to identify studies reporting cardiovascular outcomes in patients treated with BTKi. Eligible studies included studies with direct comparisons of ibrutinib, acalabrutinib, or Zanubrutinib. A triple-arm Bayesian network meta-analysis was conducted using a random-effects model. Markov Chain Monte Carlo simulations were performed using four chains and relative risks (RR) with 95% credible intervals (CrI) were estimated. Local inconsistency was assessed using node-splitting for comparisons supported by both direct and indirect evidence. Statistical analyses were performed using program R version 4.4.3. Results: A total of 10 studies were included in the final analysis. Compared with ibrutinib, both acalabrutinib (RR 0.43, 95% CrI: 0.32–0.53) and zanubrutinib (RR 0.34, 95% CrI: 0.23–0.49) were associated with significantly lower risks of atrial fibrillation ( Figure 1 ). For hypertension, acalabrutinib showed a significant reduction in risk compared to ibrutinib (RR 0.52, 95% CrI: 0.26–0.92), while zanubrutinib demonstrated no statistically significant difference (RR 0.89, 95% CrI: 0.41–1.90) ( Figure 2 ). Regarding the risk of any cardiac event, acalabrutinib again showed significantly reduced odds (OR 0.44, 95% CrI: 0.20–0.85), while zanubrutinib was non-significant (RR 0.87, 95% CrI: 0.37–1.90) ( Figure 3 ). No statistically significant differences were observed between acalabrutinib and zanubrutinib for any outcome, and node-splitting analyses showed no evidence of inconsistency (atrial fibrillation p = 0.8915; any cardiac event p = 0.907). Conclusion: In this Bayesian network meta-analysis, acalabrutinib demonstrated a lower risk of atrial fibrillation, hypertension, and any cardiac event compared to ibrutinib, while zanubrutinib was associated with reduced risk of atrial fibrillation but showed no significant differences for other outcomes.