New research findings confirm the need for caution when prescribing a phosphodiesterase-5 inhibitor (PDE5i) for the treatment of erectile dysfunction (ED) in men with heart disease using nitrate medications. In a large Swedish population study of men with stable coronary heart disease (CHD), the combined use of PDE5i and nitrates was associated with a higher risk of cardiovascular (CV) morbidity and mortality. Despite current recommendations against prescribing PDE5i to patients taking organic nitrates, both are frequently prescribed in clinical practice, leading to an increased risk of adverse cardiovascular outcomes.
Based on the results, the lead author, Ylva Trolle Lagerros, MD, PhD, of the Karolinska Institutet in Stockholm, Sweden, suggests that careful, patient-centered considerations should be made before prescribing PDE5 inhibitors to individuals with stable CHD taking nitrate medications, weighing the benefit of the medication against the potential increased risk for adverse cardiovascular outcomes.
The study, published online in the Journal of the American College of Cardiology (JACC), utilized the Swedish patient and prescription drug registers to assess the association between PDE5i treatment and cardiovascular outcomes in men with stable CHD treated with nitrate medications. The study found that the combined use of PDE5i and nitrates was associated with an increased relative risk for all outcomes assessed, including total mortality, cardiovascular and non-cardiovascular mortality, myocardial infarction, heart failure, heart revascularization, and major adverse cardiovascular events.
However, the authors also noted that the incidence of events 28 days after taking a PDE5i prescription was lower, with lower incidence rates compared to subjects taking only nitrates, indicating a low immediate risk for each event.
In a commentary in JACC, Dr. Glenn Levine from Baylor College of Medicine in Houston, Texas, highlighted the relationship between ED and coronary artery disease (CAD), noting that PDE5is are generally safe for most patients with stable CHD and mild angina, as long as they are not under chronic nitrate therapy. For those with chronic oral nitrate therapy, use of PDE5is should be considered unwise at best and generally contraindicated.
Levine suggested that for some patients under oral nitrate therapy who wish to use a PDE5i, it may be reasonable to initiate a several-week trial without nitrates (or another course of anti-anginal therapy) and assess if the patient remains relatively free of angina. For patients with infrequent angina, it may be prudent to prescribe PDE5i after a detailed discussion about the risks of temporary combination with sublingual nitroglycerin.
Levine recommended that these patients should be instructed not to take nitroglycerin within 24 hours of using a shorter-acting PDE5i or within 48 hours of using the longer-acting PDE5i tadalafil. They should also be advised to call 911 if angina develops during intercourse and does not resolve after sexual activity, and to inform medical personnel that they have recently used a PDE5i.
The study was funded by the Stockholm Region, the Center for Innovative Medicine, and the Karolinska Institutet. The researchers and editors reported no relevant conflicts of interest.