Avoiding Scary Cardiovascular Drug Toxicities

Volume 8, Issue 4

Many medications have been approved for market and later found to be cardiotoxic. The weight loss product fenfluramine/phentermine was found to damage heart valves, and thiazolidinediones were associated with exacerbation of heart failure. Minimizing cardiovascular (CV) toxicity is therefore paramount. In honor of Halloween, this week’s issue of Talking Therapeutics will focus on some new data related to cardiovascular toxicity of commonly used medications.

Point One: Beware of Scary Stimulants in the Elderly

Use of stimulants continues to increase among older adults for a variety of indications. An association between stimulant use and increased risk of CV events has been established among children and young adults, but few studies have explored the risk of CV events among older patients, a group with increased baseline risk.

A propensity-matched analysis in the Journal of the American Medical Association this week found that stimulant initiation was associated with increased risk of CV events at 30 days (hazard ratio [HR], 1.4; 95% CI, 1.1-1.8) but not at 180 days (HR, 1.2; 95% CI, 0.9-1.6) or 365 days (HR, 1.0; 95% CI, 0.6 to 1.8). In the secondary analysis, stimulant initiation was associated with increased risk of ventricular arrhythmias (HR, 3.0; 95% CI, 1.1-8.7) and stroke or transient ischemic attack (HR, 1.6; 95% CI, 1.1-2.1) at 30 days.

This cohort study found that stimulant use was associated with an early increase in CV events among older adults (with no association for long-term use), so tread carefully and monitor patients early for scary drug side effects after starting stimulants.

Point Two: Tread Carefully With CAR-T

Pivotal trials of chimeric antigen receptor T-cell (CAR-T) therapy have demonstrated significant improvements in treating a variety of myelogenous malignancies. While prior studies have evaluated cardiovascular toxicity, few were adequately powered.

In the Journal of the American College of Cardiology this week, authors of a pharmacovigilance study used the Food and Drug Administration’s adverse event reporting system to identify CV toxicities associated with axicabtagene-ciloleucel and tisagenlecleucel. Compared with the full database, CAR-T was associated with over-reporting of tachyarrhythmias (n=74 [2.8%], adj.ROR=2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n=69 [2.6%], adj.ROR=3.51 [2.42-5.09]), and pericardial diseases (n=11 [0.4%], adj.ROR=2.26 [1.25-4.09], all IC₀₂₅>0). Atrial fibrillation (n=55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14).

These data are very important for informing patients and caregivers about the full spectrum of the risks and benefits of CAR-T therapy for patients with leukemia and lymphoma.

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