Combined Erectile Dysfunction, Chest Pain Drug Use May Increase Mortality Risk

Daniel Peter Andersson, MD, PhD

Credit: Karolinska Institute

A new study found common erectile dysfunction medications prescribed in combination with common chest pain medication may increase the risk of morbidity and mortality in men with cardiovascular disease (CVD).¹

Results from the analysis indicate phosphodiesterase type 5 inhibitors (PDE5i), a common medication prescribed for erectile dysfunction in men with CVD, combined with nitrate medications, put men with CVD at an increased risk for negative health outcomes.

“Physicians are seeing an increase of requests for erectile dysfunction drugs from men with cardiovascular diseases,” said Daniel Peter Andersson, MD, PhD, a senior study author and an associate professor at the Karolinska Institute in Stockholm, Sweden.² “While there is a positive association of erectile dysfunction medications for men with CVD, patients taking nitrates may experience an increased risk of negative health outcomes.”

The study functioned as an update to previous analyses led by Andersson and colleagues using the same Swedish dataset from the Swedish Patient Register. The team assessed the link between PDE5i treatment and cardiovascular outcomes in men with stable CAD who are treated with nitrates. This study set out to clarify conflicting data on the impact of PDE5i treatment on cardiovascular morbidity and mortality.

Erectile dysfunction is common among middle-aged and older men and is an important predictive factor of coronary artery disease (CAD). Nitrates are prescribed to treat angina – both medications lead to drops in blood pressure, and they are traditionally contraindicated for use together. Andersson and colleagues indicated a growing number of people are prescribed both medications, but there are few real-world data sets on these implications.

The study included 61,487 men with a history of myocardial infarction or percutaneous coronary intervention who had received two nitrate prescriptions within six months. Study criteria defined exposure as ≥2 filled prescriptions of any PDE5i medications. Overall, the analysis consisted of 55,777 men undergoing nitrate treatment and 5,710 undergoing nitrate and PDE5i treatment analysis.

Overall follow-up occurred over a median of 5.7 years in nitrate-only users and 3.4 years in nitrate users with PDE5i treatment. Those in the nitrate and PDE5i group were younger at an average of 61.2 years, compared to 70.3 years in the nitrate-only group. For analysis, investigators used multivariable Cox proportional hazard regression to estimate hazard ratios for outcomes including all-cause mortality, cardiovascular and non-cardiovascular mortality, myocardial infarction, heart failure, cardiac revascularization, and major cardiovascular events (MACE).

Analyses revealed the combined use of PDE5i treatment with nitrates was associated with an increased risk of all health outcomes when compared with taking nitrates alone. However, among those taking both PDE5i and nitrates, the results showed few events occurred 28 days after dispensing of the PDE5is, with lower incidence rates than those taking nitrates. Andersson and colleagues suggested there is a low immediate risk for an event.

However, the results in the current study were limited by the inability to understand a patient’s compliance with their medication, as well as the inability to determine the causality of death in the data. The patient population was also considered high-risk, as they had previously experienced myocardial infarction or revascularization, and had been previously prescribed nitrates and PDE5is. As a result, Andersson and colleagues suggested the results may not be fully applicable to the general population.

“Our goal is to underscore the need for careful patient-centered consideration before prescribing PDE5i medication to men receiving nitrate treatment,” Andersson said.² “Furthermore, it justifies our efforts for continued research into the ambiguous effects of ED drugs on men with CVD.”

References

1. _{Trolle Lagerros, Y, Grotta, A, Freyland, S. et al. Risk of Death in Patients With Coronary Artery Disease Taking Nitrates and Phosphodiesterase-5 Inhibitors. J Am Coll Cardiol. 2024 Jan, 83 (3) 417–426.
   https://doi.org/10.1016/j.jacc.2023.10.041}
2. _{ACCmediacenter. Erectile dysfunction medications may increase risk of death when combined with common chest pain medication. EurekAlert! January 15, 2024. Accessed January 15, 2024. https://www.eurekalert.org/news-releases/1031060.}