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

Author:

Han Ja-Young1,Seo Young-Eun2,Kwon Jae-Hee1,Kim Jae Hyun3ORCID,Kim Myeong Gyu14ORCID

Affiliation:

1. Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea

2. Graduate School of Clinical Biohealth, Ewha Womans University, Seoul 03760, Republic of Korea

3. School of Pharmacy, Jeonbuk National University, Jeonju 54896, Republic of Korea

4. College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea

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.

Funder

National Research Foundation of Korea

Publisher

MDPI AG

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