Cardioprotective effects of PARP Inhibitors: A meta-analysis of animal studies

Abstract

Poly(adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitors are expected to provide benefits to the cardiovascular system. However, the cardioprotective effect of PARP inhibitors has not been systematically reviewed or quantitatively analyzed. This study aimed to assess the cardioprotective effects of PARP inhibitors through a meta-analysis of animal studies. Three databases PubMed, Web of Sciences, and Embase were searched until September 1, 2023. The risk of bias was assessed using SYRCLE's Risk of Bias. A total of 74 animal studies that investigated the cardiac function of PARP inhibitors compared to placebo or vehicle, were included. Outcome measures were hemodynamic indexes, cardiac contractility, and biomarkers of myocardial injury. Pooled effect size was estimated using a random-effects model with RevMan 5.4. PARP inhibitors were associated with enhanced hemodynamic indexes, including cardiac output (standardized mean difference, 0.86 [95 % CI, 0.54 to 1.17]; p < 0.00001) and stroke volume (0.42 [0.07 to 0.76]; p = 0.02). PARP inhibitors were associated with increased cardiac contractility, including ejection fraction (0.71 [0.42 to 1.01]; p < 0.00001) and fractional shortening (0.96 [0.62 to 1.31]; p < 0.00001). PARP inhibitors were associated with decreased troponin & Iukcy; (-1.42 [-2.16 to -0.68]; p = 0.0002), plasma B-type natriuretic peptide (-0.95 [-1.56 to -0.33]; p = 0.003), creatine kinase (-1.81 [-2.63 to -0.99]; p < 0.0001), and infarct size (-1.58 [-2.01 to -1.14]; p < 0.00001). PARP inhibitors improve cardiac functions and attenuate myocardial injury in animals, which indicate the cardioprotective effects. Further human studies are necessary.