Pharmacovigilance-Based Safety Profile of Bortezomib: A Disproportionality Analysis Using FAERS Data

Bortezomib is a 26S proteasome inhibitor used to treat multiple myeloma and systemic amyloidosis. While effective in prolonging survival, bortezomib has been increasingly associated with cardiovascular adverse events (CVAEs), including cardiac failure and arrhythmias, yet a comprehensive post-marketing cardiac safety profile remains incompletely defined. We analyzed cardiovascular adverse events reported between May 2003 and May 2025 using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) via the OpenVigil 2.1 platform. Disproportionality analysis was performed using reporting odds ratios (RORs) with 95% confidence intervals (CIs). Among over 9 million drug-related adverse events in FAERS, 552 cardiac events were linked to bortezomib. Several cardiac outcomes, including atrial flutter, left ventricular dysfunction, cardiac failure, cardiomyopathy, atrial fibrillation, right ventricular failure, myocarditis, and supraventricular tachycardia, demonstrated elevated disproportionality signals. Separately, cardiac amyloidosis exhibited the highest disproportionality signal (ROR: 35.58; 95% CI: 28.16–44.95), a finding that reflects underlying disease severity rather than treatment-emergent cardiotoxicity. Cardiac failure accounted for the greatest number of hospitalizations (301) and deaths (208), followed by atrial fibrillation and cardiac amyloidosis. Older adults (≥65 years) and patients with amyloidosis or multiple myeloma were the most vulnerable populations. Overall, bortezomib was associated with serious cardiac adverse events, particularly cardiac failure and atrial arrhythmias, underscoring the need for routine cardiovascular risk assessment and proactive monitoring in high-risk patients.