Cardioprotective Effects of PARP Inhibitors: A Re-Analysis of a Meta-Analysis and a Real-Word Data Analysis Using the FAERS Database

Abstract

Objective: This study aimed to assess the potential of PARP inhibitors to prevent cardiotoxicity. Methods: First, a re-analysis and update of a previously published study was conducted. Additional searches were conducted of the PubMed and Cochrane Central Register of Controlled Trials databases on 2 June 2023. After the selection process, the pooled odds ratio (OR) for cardiac adverse events (AEs) was calculated. Second, the FAERS database was examined for 10 frequently co-administered anticancer agents. The reporting odds ratio (ROR) was calculated based on the occurrence of cardiac AEs depending on the co-administration of PARP inhibitors. Results: Seven studies were selected for the meta-analysis. Although not statistically significant, co-administration of PARP inhibitors with chemotherapy/bevacizumab decreased the risk of cardiac AEs (Peto OR = 0.61; p = 0.36), while co-administration with antiandrogens increased the risk of cardiac AEs (Peto OR = 1.83; p = 0.18). A total of 19 cases of cardiac AEs were reported with co-administration of PARP inhibitors in the FAERS database. Co-administration of PARP inhibitors with chemotherapy/bevacizumab significantly decreased the risk of cardiac AEs (ROR = 0.352; 95% confidence interval (CI), 0.194–0.637). On the other hand, for antiandrogens co-administered with PARP inhibitors, the ROR was 3.496 (95% CI, 1.539–7.942). The ROR for immune checkpoint inhibitors co-administered with PARP inhibitors was 0.606 (95% CI, 0.151–2.432), indicating a non-significant effect on cardiac AEs. Conclusion: This study reports that PARP inhibitors show cardioprotective effects when used with conventional anticancer agents.

Keywords

• PARP inhibitors
• cardiac adverse events
• combination
• meta-analysis
• FAERS