People who take the drug phosphodiesterase-5 inhibitors (PDE5i) – a common medication for erectile dysfunction – are at higher risk of early death when they use it along with nitrates, a medication for chest pain, a new study has revealed.

Erectile dysfunction is a common condition in middle-aged and older men that makes it difficult to get and keep an erection. It can occur due to several causes, such as obesity, diabetes, heart disease, Parkinson's disease, multiple sclerosis, use of certain prescription medications, alcoholism and tobacco use.

Although PDE5i and nitrates should not be used together as they cause a drop in blood pressure, the number of people who are prescribed both is increasing. However, there are not many studies based on real-world data that have looked into the implications of using them together.

"Physicians are seeing an increase in requests for erectile dysfunction drugs from men with cardiovascular diseases. While there is a positive association of ED medication for men with CVD (cardiovascular disease), patients taking nitrates may experience an increased risk of negative health outcomes," said senior author Daniel Peter Andersson, from Karolinska Institutet in Stockholm.

The findings of the study were published in the Journal of the American College of Cardiology.

Researchers evaluated 61,487 men who had a myocardial infarction or percutaneous coronary intervention (angioplasty to open up blocked blood vessels) and received two nitrate prescriptions within six months. The team also followed up with those patients who had at least two filled prescriptions of any PDE5i medications.

Of the total participants, 55,777 men were treated with nitrates, and 5,710 were treated with both nitrates and PDE5i. Researchers noticed that the group that used both medications was younger at 61.2 years compared to 70.3 years in the nitrate-only users.

"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 a low immediate risk for an event," researchers said in a news release.

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

Researchers could not confirm if the patients were compliant with the medications prescribed to them. The study has also not looked into the causality of death.

The participants were people at high risk who already had a heart attack or revascularization to improve blood flow to the heart. They were given nitrate medications at least twice, and despite the recommended guidelines, they were also prescribed erectile dysfunction drugs (PDE5i) at least twice. So, the findings may not apply to the general population.

In an editorial comment, Dr. Glenn N. Levine, Baylor College of Medicine, and Michael E. DeBakey, VA Medical Center in Houston, said PDE5i is reasonably safe in patients with ischemic heart disease and mild angina with reasonable exercise ability if they are not on chronic nitrate therapy. However, the use is contraindicated in those on chronic oral nitrate therapy.

"ED (erectile dysfunction ) and CAD (coronary artery disease) are unfortunate, and all too common, bedfellows. But, as with most relationships, assuming proper precautions and care, they can co-exist together for many years, perhaps even a lifetime," Dr. Levine said.

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