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), such as cardiac failure and arrhythmias. However, a comprehensive post-marketing safety profile has not been fully established. 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 Open Vigil 2.1 platform. Disproportionality analysis was conducted using the reporting odds ratio (ROR) with 95% confidence intervals (CI) to detect statistically significant adverse reports. Of over 9 million drug-related adverse events in the FAERS database, 552 Cardiac events were linked to bortezomib. Cardiac amyloidosis showed the strongest association (ROR: 35.58; 95% CI: 28.16–44.95), followed by atrial flutter (ROR: 4.34; 95% CI: 3.41–5.52), left ventricular dysfunction (ROR: 4.25; 95% CI: 3.26–5.55), cardiac failure, acute (ROR: 3.66; 95% CI: 2.75–4.86), congestive cardiomyopathy (ROR: 3.23; 95% CI: 2.33–4.49), hypertrophic cardiomyopathy (ROR: 3.44; 95% CI: 1.95–6.08), cardiac failure (ROR: 3.18; 95% CI: 2.93–3.46), cardiomyopathy (ROR: 2.81; 95% CI: 2.30–3.43), atrial fibrillation (ROR: 2.65; 95% CI: 2.43–2.89), right ventricular failure (ROR: 2.30; 95% CI: 1.63–3.24), myocarditis (ROR: 2.25; 95% CI: 1.73–2.91), and supraventricular tachycardia (ROR: 2.17; 95% CI: 1.61–2.93). cardiac failure led to the highest number of hospitalizations (301) and deaths (208), followed by atrial fibrillation and cardiac amyloidosis. Older adults (≥65 years) and patients with amyloidosis or myeloma were the most vulnerable groups. Bortezomib is associated with a wide spectrum of serious cardiac adverse events, with cardiac amyloidosis and cardiac failure demonstrating particularly high disproportionality and mortality. These findings emphasize the need for routine cardiovascular risk assessment and proactive monitoring in high-risk patient populations receiving bortezomib.