Taking both erectile dysfunction and chest pain drugs linked with early death risk, study finds

By Kristen Rogers, CNN

(CNN) — For erectile dysfunction in men with cardiovascular disease, the ED drug phosphodiesterase-5 inhibitors — also known as PDE5i — is a common treatment.

But in a new study of more than 60,000 men, taking this medication along with nitrates, a common drug for chest pain, increased risks of negative health outcomes such as heart failure and early death, according to the study published Monday in the Journal of the American College of Cardiology.

“Our goal is to underscore the need for careful patient-centered consideration before prescribing PDE5i medication to men receiving nitrate treatment,” said the study’s senior author Dr. Daniel Peter Andersson, an associate professor in the department of medicine at the Karolinska Institute in Stockholm, in a news release. “Furthermore, it justifies our efforts for continued research into the ambiguous effects of ED drugs on men with (cardiovascular disease).”

A known yet increasing problem

The use of PDE5i in people with both ED and cardiovascular disease has been controversial since the drug and nitrates both induce hypotension, or low blood pressure, by working on endothelial cells in different ways. Endothelial cells line blood vessels and regulate exchanges between the blood and surrounding tissues. Previous studies on the benefits or harms of simultaneous use have been mixed.

But despite this existing research and clinical guidelines discouraging simultaneous use of the medications, “physicians are seeing an increase of requests for erectile dysfunction drugs from men with cardiovascular diseases,” Andersson said.

The study included 61,487 men from the National Swedish Patient Registry with a stable coronary artery disease and a history of myocardial infarction — a heart attack — or percutaneous coronary intervention between 2005 and 2013. Percutaneous coronary intervention, also known as revascularization, is a nonsurgical procedure that treats blockages in a coronary artery by opening up blocked or narrowed sections of the artery, restoring blood flow to the heart, according to Yale Medicine.

Participants also had received two prescriptions of nitrates — sublingual nitroglycerin or oral nitrates — within six months. The authors looked into the effects of also having received at least two filled prescriptions of the PDE5i medications sildenafil, vardenafil or tadalafil.

Of these participants, 55,777 men had been treated with nitrates alone, while 5,710 were treated with both nitrates and PDE5i. The average follow-up time and age in the nitrate group was 5.7 years and around 70 years old, respectively; for the combination group it was 3.4 years and around 61 years old.

The combination group had a slightly higher risk of premature death from all causes. The risk for having undergone revascularization during the follow-up period was twice that of the nitrates-only group.

Dr. Howard C. Herrmann, the John W. Bryfogle Professor of Cardiovascular Diseases at the University of Pennsylvania, wasn’t surprised by the main findings.

Experts “have known about the potential risk of low blood pressure with this combination of therapies for decades … (and) about the co-existence of erectile dysfunction in many patients with CAD due to both diseases having endothelial dysfunction,” Herrmann, who wasn’t involved in the study, said via email.

But he was “most surprised by the high frequency (9%) of patients who were prescribed both medications,” Herrmann, also the section chief of interventional cardiology at the Hospital of the University of Pennsylvania, added. “It should serve as an additional warning to physicians about the co-prescription of these medications.”

What patients should know

The study does have weaknesses, including “not knowing exactly how patients took both medications: the timing, how often, what instructions they were given in this regard, which types of nitrates and PDE5i (with their different half-lives),” Herrmann said. Half-life refers to how long it takes for the amount of a drug’s active ingredient in your body to reduce by half, or how long a drug is active.

“In addition, this type of analysis cannot prove causality and it may be that the need for PDE5i (e.g., ED) is a marker for more severe disease rather than that the medication is the cause of more events,” Herrmann added.

Having more definite conclusions about the effects of the medication combination on health would require “a randomized study where patients were either given PDE5 inhibitors and nitrates, or nitrates randomly,” said Dr. Dimitrios Terentes-Printzios, an interventional cardiologist in the first cardiology department of the National and Kapodistrian University of Athens in Greece, via email. Terentes-Printzios wasn’t involved in the study.

Generally, these medications shouldn’t be used together, Herrmann said.

But “patients with ED who want to use a PDE5i should discuss with their physician other ED treatment options as well as the need for nitrates (and alternatives) and be instructed about the timing of how to take both medications,” Herrmann said. “For example, a patient who takes a PDE5i, has sex and then develops angina should not take a nitrate medication to treat it, but should seek medical attention.”

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