(307) Cardiovascular Adverse Events Associated with PARP Inhibitors: A Disproportionality Analysis of FDA Adverse Event Reporting System

Publication Number: 981

Background: Poly Adenosine diphosphate- Ribose Polymerase (PARP) inhibitors are targeted therapies used to treat cancer, mainly ovarian cancer, fallopian tube cancer, breast cancer and prostate cancer, but the incidence of cardiovascular adverse events (CVAEs) associated with them is not well established.

Objectives: To analyse the cardiovascular safety profile of PARP inhibitors using the FDA Adverse Event Reporting System (FAERS) database.

Methods: The key features of PARP inhibitor-related cardiovascular adverse events were characterised using disproportionality analysis in publicly available FAERS database using Open Vigil 2.1 (2014Q1-2021Q3). The drugs under study were Talazoparib, Niraparib and Olaparib. As the events of interest, all cardiovascular AEs that fall under the system organ classification of "Cardiovascular disorders" as per MedDRA-v24 were used. Proportional reporting ratio (PRR) and Reporting odds ratio (ROR) were the main parameters for generating safety signals. Value of ROR-1.96SE>1 and PRR≥2 with an associated χ2 value of 4 was considered the threshold for a signal.

Results: PARP inhibitors accounted for 14,199 total events in the FAERS database, of which 2396 reports(16.9%) were associated with the cardiovascular system. Most significant signals were obtained for angina bullosa haemorrhagica [ROR=32.4 (95% CI=10.3-102)], increased blood pressure [ROR=21.1(19.7-22.6)] and vein rupture [ROR=12.4(4-38.6)] for Niraparib, while ventricular arrhythmia [ROR=63.3(23.6-169.8)] and vascular rupture [ROR=8.3(2.7-25.8)] were seen to be most associated with Talazoparib and Olaparib respectively. The observed demographics were of median age 71 (IQR-63-76) years for Niraparib, 61 (55-67) years for Olaparib, and 75 years for Talazoparib. Most cases with talazoparib were reported among males(n=4) with metastatic prostrate cancer, whereas females (n=17) with ovarian, breast and fallopian tube cancer experienced most cardiovascular adverse events with Olaparib. In the case of Niraparib, CVAEs were seen more in females (n=1479) than males(n=4). Most deaths were seen among Niraparib and Olaparib (n=29;4), while life-threatening conditions were developed among all three drugs. (n=81;3;3 for Niraparib, Olaparib and talazoparib, respectively)

Conclusions: While analysing spontaneous reporting data, cardiovascular adverse events with Talazoparib, Olaparib, Niraparib were identified. The maximum number of these adverse events were associated with Niraparib. More studies with superior epidemiological study design should be undertaken to study the association and risk in compromised patients.