Viagra combined with chest pain medication could increase risk of death

Combining erectile dysfunction drugs (such as Viagra, Levitra, and Cialis) with a common chest pain medication (nitrate) may increase the risk of death, according to international researchers who say these medications are often prescribed together, despite this combination not being recommended. The team looked at Swedish national data including 55,777 men with heart issues treated with nitrates and 5,710 treated with both nitrates and erectile dysfunction medication. The team found those prescribed both medications experienced a greater overall risk of death from any cause, and death from heart issues.  An accompanying editorial says these results, combined with previous (albeit weaker) studies that did not find a higher risk, indicate we should probably continue to consider the drug combination as ill advised, but discuss the risks with patients in cases where the combinations are required.

Journal/conference: Journal of the American College of Cardiology

Link to research (DOI): 10.1016/j.jacc.2023.10.041

Organisation/s: Karolinska Institutet, Sweden

Funder: Dr Trolle Lagerros was funded by the Stockholm County Council
(clinical research appointment). Dr Andersson was funded by the
Stockholm County Council (no. 954970, 963296, 962029), CIMED, and
the Strategic Research Program at Karolinska Institutet (no. 961507).
None of the funders were involved in the design, conduct of the
study, data collection, data analysis, interpretation of data, or preparation,
review, or approval of the manuscript. Dr Andersson has
received nonfinancial support from COVIS Pharma (study drug
donation) as principal investigator in another study; is site principal
investigator for Ionis 678354 for Ionis Pharmaceuticals; and is
employed at Werlabs; none of these studies or the outside employment
are related to the present work. All other authors have reported
that they have no relationships relevant to the contents of this paper
to disclose.

Media release

From: American College of Cardiology

 Erectile Dysfunction Medications May Increase Risk of Death When Combined with Common Chest Pain Medication

 Medications are contraindicated but often prescribed together

 WASHINGTON (Jan. 15, 2024) – Phosphodiesterase type 5 inhibitors (PDE5i)—an erectile dysfunction drug sold under the names Viagra, Levitra, Cialis, and others—are a common medical treatment for erectile dysfunction (ED) in men with cardiovascular disease (CVD). However, a new Swedish study published today in 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 both prescribed.

 Erectile dysfunction is a common condition in middle-aged and older men and is a strong predictor of coronary artery disease. Nitrates are medications commonly used to treat angina, or chest pain. Both can cause drops in blood pressure, so they are contraindicated for use together. However, there is little real-world data on the implications of using both and the number of people who are prescribed both is growing.

 Serving as an update to previous studies using the same 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 are being treated with nitrates. It aims to resolve the conflicting results regarding the impact of PDE5i treatment on cardiovascular morbidity and mortality.

 “Physicians are seeing an increase 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 author of the study. “While there is 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 within six months. Exposure was defined as having received at least two filled prescriptions of any PDE5i medications. Among these men, 55,777 men were treated with nitrates and 5,710 were treated with both nitrates and PDE5i. Median follow-up time for the entire cohort was 5.7 years in nitrate only users and 3.4 years in nitrate users with PDE5i treatment. The nitrate plus PDE5i group was younger at 61.2 years compared to 70.3 years in 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 results of the study indicate that the combined use of PDE5i treatment with nitrates is associated with a higher risk for all health outcomes compared to 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.

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

 Limitations of the study include the inability to know a patient’s compliance and medication habits and the inability to infer causality of death from the data. Researchers assessed usage by filled prescriptions but did not know how 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 at least twice and despite guideline recommendations also prescribed PDE5i at least twice; thus, results may not be entirely generalizable to the general population. Further investigation is needed to fully understand the effects of the combination 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 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 

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