Cardiac adverse events with PARP inhibitors: Real world pharmacovigilance study using FAERS database.

Abstract

e24011 Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) effectively target BRCA1/BRCA2-mutated tumors by exploiting dysfunctional homologous recombination pathways while sparing normal cells. Sporadic cardiac and vascular events, particularly with niraparib, have been reported due to off-target effects. Methods: This study evaluates real-world data on PARPi-associated cardiac events using the FDA Adverse Event Reporting System (FAERS) database.The FAERS database was queried on January 25, 2025, using product-specific terms (“Olaparib,” “Rucaparib,” “Rucaparib camsylate,” “Niraparib,” “Niraparib Tosylate monohydrate,” “Talazoparib,” and “Talazoparib Tosylate”), identifying 1,925 cardiac events. Descriptive statistics and disproportionality analyses were conducted, with the reporting odds ratio (ROR) and 95% confidence intervals (CI) calculated. An ROR was considered significant if the lower limit of the 95% CI exceeded 1. Results: The ROR (95% CI) for arrhythmias was 1.56 (1.36–1.80) for niraparib and 3.01 (1.86–4.87) for talazoparib compared to all other drugs in FAERS. Conclusions: Higher RORs for arrhythmias were observed with Niraparib and Talazoparib compared to other drugs in FAERS. While these findings suggest potential safety signals, they do not establish causality and warrant larger studies to evaluate these associations. Baseline demographics for all cardiac events and ROR for specific cardiac events divided in 5 subgroups for PARPi. Baseline characteristics Olaparib N=15,558 RucaparibN=8523 NiraparibN= 20325 TalazoparibN=1177 Years included Inception-2024 Inception-2024 Inception-2024 Inception-2024 Cardiac Disorders N= 407 N=164 N= 1304 N=50 Cardiac Failure 90 (22.1%) 19 (11.6%) 60 (4.6%) 6 (12%) Ischemic heart disease 75 (18.4%) 29 (17.6%) 102 (7.8%) 11(22%) Arrhythmias 84 (20.6%) 25 (15.2%) 198 (15.2%) 17 (34%) Myopericarditis 13(3.2%) 5 (3.0%) 5 (0.4%) NR Cardiac Arrest 22(5.4%) 4 (2.4%) 10 (0.8%) 4 (8%) Age<18 years18-6465-85>85Not specified NR101(24.8%)130(31.9%)5 (1.2%)171(42%) NR40 (24.4%)48 (29.3%)2 (1.2%)74 (44.1%) NR224 (17.2%)252 (19.3%)10 (0.8%)818 (62.7%) 1 (2%)10 (20%)34 (68%)0 (0)5 (10%) GenderMalesFemalesNot specified 92 (22.6%)291 (71.5%)24 (5.9%) 14 (8.5%)135 (82.3%)15 (9.1%) 26 (2%)789 (60.5%)489 (37.5%) 30 (60%)16 (32%)4 (8%) Cardiac failure 0.88(0.72,1.09) 0.38(0.24,0.60) 0.50(0.39,0.65) 1.75(0.78,3.91) Ischemic Heart disease 0.46(0.37,0.58) 0.38(0.26,0.54) 0.58(0.47,0.70) 1.24(0.688,2.25) Arrhythmias 0.63 (0.50,0.78) 0.66(0.44,0.98) 1.56(1.36,1.80) 3.01(1.86,4.87) Myopericarditis 1.12 (0.65,1.93) 0.07(0.03,0.18) 0.33(0.13,0.79) NR Cardiac arrest 0.30(0.19,0.45) 0.10(0.03,0.26) 0.10(0.05,0.19) 1.05(0.39,2.80) NR -Not reported.