Phosphodiesterase type 5 inhibitors (PDE5i) are a common medical treatment for erectile dysfunction (ED) in men with cardiovascular disease. However, a study published Jan. 15 in JACC suggests that patients are at higher risk for morbidity and mortality over time when PDE5is and nitrate medication are both prescribed.

Ylva Trolle Lagerros, MD, et al., looked at 61,487 men from the Swedish Patient Register with a history of myocardial infarction (MI) or PCI who had received two nitrate prescriptions within six months. Exposure was defined as having received at least two filled prescriptions of any PDE5i medications. Among these men, 55,777 were treated with nitrates and 5,710 were treated with both nitrates and PDE5i.

Results of the study indicate that the combined use of PDE5i treatment with nitrates is associated with higher mortality (HR: 1.39; 95% CI: 1.28-1.51), cardiovascular mortality (HR: 1.34; 95% CI: 1.11-1.62), noncardiovascular mortality (HR: 1.40; 95% CI: 1.27-1.54), MI (HR: 1.72; 95% CI: 1.55-1.90), heart failure (HR: 1.67; 95% CI: 1.48-1.90), cardiac revascularization (HR: 1.95; 95% CI: 1.78-2.13), and major cardiovascular events (HR: 1.70; 95% CI: 1.58-1.83), vs. those taking nitrates alone. In those taking both PDE5i and nitrates, few events occurred 28 days after dispensing the PDE5is, with lower incidence rates than in subjects taking nitrates, indicating that there is low immediate risk for an event.

“Physicians are seeing an increase of requests for ED drugs from men with cardiovascular diseases,” said Daniel Peter Andersson, MD, PhD, senior author of the study. “Our goal is to underscore the need for careful patient-centered consideration before prescribing PDE5i medication to men receiving nitrate treatment. Furthermore, it justifies our efforts for continued research into the ambiguous effects of ED drugs on men with cardiovascular disease.”

In an accompanying editorial comment, Glenn N. Levine, MD, FACC, said in patients with ischemic heart disease and only mild angina with reasonable exercise ability, ED PDE5i are reasonably safe – if the patient is not on chronic nitrate therapy. However, in those on chronic oral nitrate therapy, use of PDE5i is ill-advised at best and generally contraindicated.

“ED and CAD are unfortunate, and all too common, bedfellows,” Levine said. “But, as with most relationships, assuming proper precautions and care, they can co-exist together for many years, perhaps even a lifetime.”