Phosphodiesterase-Type-5 inhibitors (PDE5i) – a medication for erectile dysfunction sold under the names Viagra, Levitra, Cialis, and others – are a common medical treatment for erectile dysfunction (ED) in men with cardiovascular diseases (CVD). However, a new Swedish study published today in the Journal of the American College of Cardiology suggests that patients may be at a higher risk of morbidity and mortality over time when both PDE5is and nitrate medications are prescribed.
Study: risk of death in patients with coronary heart disease taking nitrates and phosphodiesterase-5 inhibitors. Image source: New Africa / Shutterstock
Erectile dysfunction is a common condition in men of middle and older age and a strong predictor of coronary heart disease. Nitrates are medications commonly used to treat angina pectoris or chest pain. Both can cause a drop in blood pressure, so their simultaneous use is contraindicated. However, there is limited real-world data on the effects of using both medications, and the number of people prescribed both is increasing.
Building on previous studies that used the same Swedish national dataset from the Swedish Patient Register, this study analyzes the relationship between PDE5i treatment and cardiovascular outcomes in men with stable coronary heart disease (CHD) being treated with nitrates. The goal is to resolve the conflicting results regarding the effects of PDE5i treatment on cardiovascular morbidity and mortality.
“Doctors are observing an increasing demand for erectile dysfunction medications from men with cardiovascular diseases,” said Daniel Peter Andersson, MD, PhD, associate professor at the Karolinska Institutet in Stockholm and lead author of the study. “While there is a positive association between ED medications and men with cardiovascular diseases, there may be an increased risk of negative health outcomes in patients taking nitrates.”
The study included 61,487 men with a history of myocardial infarction (MI) or percutaneous coronary intervention (PCI) who had received two nitrate prescriptions within six months. Exposure was defined as receiving at least two filled prescriptions of PDE5i medications. Of these men, 55,777 were treated with nitrates and 5,710 were treated with both nitrates and PDE5i. The mean follow-up time for the entire cohort was 5.7 years in nitrate-only consumers and 3.4 years in nitrate consumers with PDE5i treatment. The nitrate plus PDE5i group was younger at 61.2 years, compared to 70.3 years in the pure nitrate consumers.
The researchers conducted a multivariable Cox Proportional Hazard regression to estimate the Hazard Ratios (HR) with 95% confidence intervals (CI) for various health outcomes including overall mortality, cardiovascular and non-cardiovascular mortality, MI, heart failure, cardiac revascularization, and major adverse cardiovascular events (MACE).
The study’s results suggests that the combined use of PDE5i treatment with nitrates is associated with a higher risk for all health outcomes compared to those taking only nitrates. Few events occurred 28 days after the administration of PDE5is in individuals taking both PDE5i and nitrates, with incidence rates lower than those taking nitrates, indicating a low immediate risk of an event.
“Our aim is to underline the need for careful, patient-centered consideration before prescribing PDE5i medications to men receiving nitrate treatment,” said Andersson. “Additionally, it justifies our efforts to further research the unclear impacts of ED medications on men with cardiovascular diseases.”
Limitations of the study include an inability to know a patient’s compliance and medication habits and an inability to establish causality for death from the data. The researchers assessed consumption based on filled prescriptions but did not know how compliant the patients were or what their medication habits were. Additionally, the patient population included high-risk individuals who had already experienced MI or revascularization and had received nitrate and PDE5i prescriptions at least twice, contrary to guideline recommendations; therefore, the results may not be fully generalizable to the overall population. Further investigations are needed to fully understand the impacts of combination treatments.
In an accompanying editorial, Glenn N. Levine, MD, from Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, stated that ED PDE5i are reasonably safe in patients with ischemic heart disease and only mild angina pectoris with reasonable exercise capacity – if the patient is not receiving chronic nitrate therapy. However, in individuals receiving chronic oral nitrate therapy, the use of PDE5i is at best not advisable and generally contraindicated.
“ED and CAD are unfortunate and all too common bedfellows,” said Levine. “But, as with most relationships, with the right precautions and care, they can cohabitate for many years, perhaps even a lifetime.”