Cardiovascular complications of modern multiple myeloma therapy: A pharmacovigilance study.

AIMS: Multiple myeloma accounts for over 10-15% of haematological malignancies. Continued molecular advances have resulted in the development of new drugs for treatment of multiple myeloma. Four drugs were approved by the Food and Drug Administration (FDA) in 2015, but their safety is not well defined. The aim of this study is to delineate the cardiovascular adverse events of these drugs. METHODS: We reviewed the adverse cardiac events of newly approved FDA drugs since 2015 using the US FDA Adverse Events Reporting System (FAERS) database. We calculated the reporting odds ratio (ROR) with 95% confidence interval (CIs) for the drugs that have the highest incidence of cardiovascular adverse events. RESULTS: Among the medications that have approved for multiple myeloma between 2015 and 2020, 4 novel drugs showed the highest incidence of cardiotoxicity. ROR (95% CI) for atrial fibrillation due to elotuzumab, ixazomib, daratumumab and panobinostat compared to other FAERS drugs was 5.8 (4.4-7.7), 1.9 (1.5-2.3), 4.8 (4.2-5.6) and 5.7 (4.1-8.1), respectively. The ROR (95% CI) for cardiac failure was 8.2 (6.4-10.5), 4.7 (4.1-5.4), 5.8 (4.9-6.7) and 5.6 (3.8-8.1) and ROR (95% CI) for coronary disease was 2.7 (1.9-3.9), 2.7 (2.3-3.2), 2.3 (1.9-2.8) and 4.6 (3.2-6.6) due to elotuzumab, ixazomib, daratumumab and panobinostat compared to all other drugs in FAERS. CONCLUSION: Our results demonstrated that certain newly approved antimyeloma therapies are significantly associated with previously unknown cardiotoxicity. These results warrant further studies and highlight the importance of considering the cardiac history of patients with multiple myeloma when utilizing these novel agents.

Novel multiple sclerosis agents-associated cardiotoxicity: A real-world pharmacovigilance study.

BACKGROUND: Emerging novel therapeutics have been developed to hamper the progression of multiple sclerosis (MS). However, the adverse events related to these new agents remain largely unknown. Therefore, we sought to investigate the cardiovascular complications of these drugs. METHODS: Utilizing data from the U.S. food and drug administration (FDA) adverse events reporting system (FAERS), we comprehensively evaluated the cardiovascular complications of the newly FDA-approved anti-MS modifying therapies approved since 2015. Disproportionality signal analysis was conducted by measuring reporting odds ratio (ROR) with a 95% confidence interval of all cardiovascular adverse events since approval till 2021. RESULTS: After vetting the newly approved agents for MS, CD20 and CD25 inhibitors and sphingosine-1-phosphate receptors agonists were the latest approved medications for MS since 2015. Two CD20 (ocrelizumab, ofatumumab) and one CD25 inhibitors (daclizumab) were significantly associated with multiple cardiovascular adverse events. Among all the cardiotoxic events; coronary artery disease, cardiac failure and atrial fibrillation were the most predominant among CD20 or CD25 blockers. Interestingly, sphingosine-1-phosphate receptors (S1PR) agonists showed much fewer reported cardiac adverse events. However, fingolimod and siponimod were associated with significant AV block and bradycardia. CONCLUSIONS: Our data revealed the new MS agents are associated with various undefined cardiovascular complications. These findings potentially instigate further studies to personalize prescribing these agents for MS based on patient's cardiovascular profile.

Sarcopenia is a Significant Predictor of Mortality After Abdominal Aortic Aneurysm Repair.

AIMS: Repair of abdominal aortic aneurysms (AAA) decreases the incidence of rupture and death. In cancer patients, sarcopenia has been associated with increased surgical complications and mortality. The impact of sarcopenia on survival after AAA repair has yet to be described. METHODS AND RESULTS: Patient demographic, laboratory, body composition measurements and survival data were obtained from patients undergoing AAA repair at the Indiana University medical campus over a 5-year period. Univariate and multivariate analyses were performed to identify factors associated with overall survival. Overall, 58.2% presented with sarcopenia. Sarcopenic patients were older (71.8±8.3 versus 66.8±8.1 years; p<0.001), had lower body mass index (BMI) (26.3±5.2 versus 31.5±5.9 kg/m2; p<0.001), higher rates of myosteatosis (84.4% versus 52.%; p<0.001), greater AAA diameter (60.6±14.0 versus 57.8±11.7 mm; p=0.016), higher Charlson Comorbidity Index (CCI) (32.3% versus 25.1% ≥6; p=0.034), and increased rates of rupture (8.2% versus 3.8%; p=0.047). Sarcopenic and nonsarcopenic patients had no difference in 30-day morbidity (8.5% versus 8.5%; p=0.991) or mortality (3.7% versus 0.9%; p=0.07). Univariate analysis demonstrated age, sarcopenia, myosteatosis, CCI, and BMI to be associated with long-term survival. There was no correlation between BMI and sarcopenia. Both sarcopenia and myosteatosis resulted in decreased one-, three-, and five-year survivals compared to their counterparts. On multivariate analysis sarcopenia is independently associated with survival, conferring a 1.6-fold increase in death (p=0.04). The combination of sarcopenia plus myosteatosis doubled the risk of death compared to sarcopenia alone. CONCLUSIONS: This is the first study to demonstrate that over half of all patients undergoing AAA repair are sarcopenic, a condition associated with increased mortality. Sarcopenia with myosteatosis is associated with double the mortality of sarcopenia alone. CT scan, but not BMI, accurately identifies sarcopenia and myosteatosis. Defining the mechanisms through which sarcopenia contributes to late death after AAA repair is critical to developing novel interventions that may improve survival in this high risk population.