Carfilzomib was associated with a significantly increased reporting odds ratio of 11.73 for cardiac failure compared to other anticancer agents in Japanese patients with multiple myeloma.
Do proteasome inhibitors (carfilzomib, bortezomib, ixazomib) increase the risk of cardiovascular adverse events compared to other anticancer agents?
Carfilzomib and bortezomib are associated with significant cardiovascular adverse event signals compared to other anticancer agents, with risk profiles influenced by age and sex, highlighting the need for tailored cardiovascular monitoring.
Effect estimate: ROR 11.73 (carfilzomib for cardiac failure) (95% CI 10.34-13.31)
Absolute Event Rate: 11.73% vs 1%
Background/Aim: In this study, we aimed to evaluate the cardiovascular adverse event (CVAE) signals associated with three proteasome inhibitors (PIs), carfilzomib, bortezomib, and ixazomib, using the Japanese Adverse Drug Event Report (JADER) database, with anticancer agents as a reference. Patients and Methods: Spontaneous adverse event reports restricted to anticancer agents were extracted from the JADER database between April 2004 and March 2025. A disproportionality analysis was conducted for six predefined CVAE categories based on narrow Standardized MedDRA Queries. Additional analyses were stratified by age (≥70 vs. Results: In total, 12,181 CVAE reports were identified: 2,303 for carfilzomib, 6,851 for bortezomib, and 3,027 for ixazomib. The overall analysis detected multiple CVAE signals for carfilzomib and bortezomib, including cardiac failure and arrhythmia, whereas no signals were detected for ixazomib. The age-stratified analysis performed revealed new signals that were not observed overall, including venous thromboembolism in older adult patients receiving carfilzomib, cardiomyopathy in those receiving bortezomib, and cardiac failure in those receiving ixazomib. Sex-stratified analysis identified male-specific signals, including thromboembolic and arrhythmic events for carfilzomib, cardiomyopathy for bortezomib, and both cardiac failure and cardiomyopathy for ixazomib. The JADER database analysis identified multiple CVAE signals for carfilzomib and bortezomib, along with new age- and sex-specific signals not observed in the overall population. Conclusion: These findings highlight the potential influence of patient demographics on CVAE risk and support tailored monitoring strategies for patients receiving PIs, particularly older adult and male patients.
Fujiwara et al. (Fri,) conducted a other in Patients with multiple myeloma receiving proteasome inhibitors (carfilzomib, bortezomib, or ixazomib) reported with cardiovascular adverse events in Japanese clinical practice (n=12,181). Carfilzomib, Bortezomib, and Ixazomib vs. Other anticancer agents was evaluated on Reporting odds ratio (ROR) for cardiovascular adverse events (CVAE) categories compared to other anticancer agents (ROR 11.73 (carfilzomib for cardiac failure), 95% CI 10.34-13.31). Carfilzomib was associated with a significantly increased reporting odds ratio of 11.73 for cardiac failure compared to other anticancer agents in Japanese patients with multiple myeloma.