Combined use of ED drugs, nitrates linked with worse outcomes in patients with CAD

Men with stable coronary artery disease taking both a phosphodiesterase-5 inhibitor (PDE5i) and nitrates are at a heightened risk of poor cardiovascular outcomes, new research shows.

Researchers assessed outcomes from 55,777 men treated with nitrates and 5,710 men treated with nitrates and a PDE5i enrolled in two Swedish registries. All patients had a previous myocardial infarction (MI) or revascularization between 2006 and 2013. The median follow-up time was 5.7 years for patients only taking nitrates and 3.4 years in patients taking nitrates and a PDE5i. Patients taking both medications tended to be younger than those on nitrates only, with average ages of 61.2 years and 70.3 years, respectively. Patients taking a PDE5i were also healthier than their counterparts, with lower rates of heart failure, cancer, and other comorbidities. Findings were published by the Journal of the American College of Cardiology on Jan. 15.

Combined use of a PDE5i and nitrates was associated with a higher risk of overall mortality (hazard ratio [HR], 1.39; 95% CI, 1.28 to 1.51), both from cardiovascular causes (HR, 1.34; 95% CI, 1.11 to 1.62) and other causes (HR, 1.40; 95% CI, 1.27 to 1.54), than nitrate use alone. Patients taking both medications also had heightened risk of MI (HR, 1.72; 95% CI, 1.55 to 1.90), heart failure (HR, 1.67; 95% CI, 1.48 to 1.90), cardiac revascularization (HR, 1.95; 95% CI, 1.78 to 2.13), and major cardiovascular events (HR, 1.70; 95% CI, 1.58 to 1.83). There were 24,572 deaths during the follow-up period, of which 23,979 occurred in men taking nitrates only.

The researchers noted that few events occurred in the 28 days following dispensation of PDE5is, “indicating a low immediate risk for any event.” Because patients included in the study were high-risk individuals who already experienced revascularization or an MI, the results may not be generalizable to other patient populations, the authors cautioned. Another limitation to the study was a lack of data on potential confounders like body mass index, smoking status, and physical activity.

The authors concluded that “careful patient-centered consideration before prescribing PDE5is to patients with cardiovascular disease using nitrate medication is warranted.”

An accompanying editorial noted that the study did not include data on how often patients took the drugs. “In those on chronic oral nitrate therapy, we should continue to regard the use of PDE5is as ill-advised at best and generally contraindicated,” the editorialists wrote.