Phosphodiesterase type 5 inhibitors (PDE5i)-an erectile dysfunction drug sold under the names Viagra, Levitra, Cialis, and others are a standard medical treatment for erectile dysfunction (ED) in men with heart problems (CVD). Nevertheless, a brand new Swedish study published today within the Journal of the American College of Cardiology suggests that patients are at higher risk for morbidity and mortality over time when PDE5is and nitrate medication are each prescribed.

Study: Risk of Death in Patients With Coronary Artery Disease Taking Nitrates and Phosphodiesterase-5 Inhibitors. Image Credit: Recent Africa / Shutterstock

Erectile dysfunction is a standard condition in middle-aged and older men and is a robust predictor of coronary artery disease. Nitrates are medications commonly used to treat angina or chest pain. Each may cause drops in blood pressure, so that they are contraindicated to be used together. Nevertheless, there may be little real-world data on the implications of using each, and the variety of people who find themselves prescribed each is growing.

Serving as an update to previous studies using the identical Swedish national dataset from the Swedish Patient Register, this research analyzes the association between PDE5i treatment and cardiovascular outcomes in men with stable coronary artery disease (CAD) who’re being treated with nitrates. It goals to resolve the conflicting results regarding the impact of PDE5i treatment on cardiovascular morbidity and mortality.

“Physicians are seeing a rise of requests for erectile dysfunction drugs from men with cardiovascular diseases,” said Daniel Peter Andersson, MD, PhD, Associate Professor at Karolinska Institutet in Stockholm and senior creator of the study. “While there may be a positive association of ED medication for men with CVD, patients taking nitrates may experience an increased risk of negative health outcomes.”

The study included 61,487 men with a history of myocardial infarction (MI) or percutaneous coronary intervention (PCI) who had received two nitrate prescriptions inside six months. Exposure was defined as having received no less than two filled prescriptions of any PDE5i medications. Amongst these men, 55,777 men were treated with nitrates and 5,710 were treated with each nitrates and PDE5i. The median follow-up time for the complete cohort was 5.7 years in nitrate-only users and three.4 years in nitrate users with PDE5i treatment. The nitrate plus PDE5i group was younger at 61.2 years in comparison with 70.3 years within the nitrate-only users.

The researchers conducted multivariable Cox proportional hazard regression to estimate the hazard ratios (HR) with 95% confidence intervals (CI) for various health outcomes, including all-cause mortality, cardiovascular and non-cardiovascular mortality, myocardial infarction (MI), heart failure, cardiac revascularization and major cardiovascular events (MACE).

The outcomes of the study indicate that the combined use of PDE5i treatment with nitrates is related to a better risk for all health outcomes in comparison with those taking nitrates alone. In those taking each PDE5i and nitrates, few events occurred 28 days after shelling out the PDE5is, with lower incidence rates than in subjects taking nitrates, indicating that there’s a low immediate risk for an event.

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

Limitations of the study include the lack to know a patient’s compliance and drugs habits and the lack to infer causality of death from the info. Researchers assessed usage by filled prescriptions but didn’t know the way compliant patients were or what their medication habits were. Also, the patient population included high-risk individuals who already had experienced MI or revascularization. They were also prescribed nitrates no less than twice and despite guideline recommendations also prescribed PDE5i no less than twice; thus, results will not be entirely generalizable to the overall population. Further investigation is required to totally understand the consequences of the mixture of treatments.

In an accompanying editorial comment, Glenn N. Levine, MD, Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, said in patients with ischemic heart disease and only mild angina with reasonable exercise ability, ED PDE5i are reasonably protected – if the patient will not be on chronic nitrate therapy. Nevertheless, in those on chronic oral nitrate therapy, the usage of PDE5i is ill-advised at best and usually contraindicated.

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