Could taking Viagra have an additional benefit?


This transcript has been edited for clarity.

welcome to Impact factor, your weekly dose of feedback on a new medical study. I’m Dr. F. Perry Wilson from Yale School of Medicine.

All right, let’s get something out of the way. This week we talk about drugs for erectile dysfunction (ED) and long-term mortality, thanks to this study, which appears in the Journal of the American College of Cardiology.

I know, you think I’m going to be immature about this, joking around, making bad puns, that kind of thing. Well I’m sorry to disappoint you, but this is a serious comment on a serious study.

Briefly, the researchers found vas deferens between men treated with phosphodiesterase-5 (PDE5) inhibitors, such as Viagra, and those treated with alprostadil.

It is fine, I am sorry. I’ve just finished.

The background here is that it has long been established that erectile dysfunction is associated with poor cardiovascular outcomes, probably because it is a surrogate for vascular disease. Previous studies of men with erectile dysfunction found that those who received PDE5 inhibitors had lower rates of these poor outcomes than men who did not receive those drugs. But compare men who receive erectile dysfunction prescriptions with those who cannot introduce bias. The men who get those recipes are healthy enough for sexual activity, for example.

A better control group might be men with erectile dysfunction who receive another type of treatment, such as alprostadil, which is applied locally (by injection, a cream, or a urethral suppository).

The study comes from Sweden, home to a large pharmacoepidemiology, thanks to its nationwide healthcare database that includes a wealth of data on the state of healthcare, medications, and outcomes for everyone in the country.

The researchers identified around 240,000 Swedish men who had had a previous heart attack or revascularization. Of that group, about 20,000 were receiving erectile dysfunction medications, mostly PDE5 inhibitors, but enough on alprostadil to perform the analysis.


Main results: Men taking PDE5 inhibitors for erectile dysfunction were less likely to have heart attacks, coronary revascularization, or heart failure than those taking alprostadil. In fact, over the course of up to 15 years of follow-up, 14% of men died from any cause in the PDE5 group compared to 26% in the alprostadil group.


Of course, when you see results like that, you immediately think about confusing. Who are these men who use injections when there is a pill on the market that achieves the same effect? You can see here that the populations were dramatically different. Men taking alprostadil were more likely to have diabetes, COPD, stroke, and active cancer, and they were basically sicker in any way the researchers could measure.


Adjusting for all of these factors dramatically attenuated the observed benefit of PDE5 inhibitors, but did not eliminate it. The class was still associated with lower rates of cardiovascular and all-cause mortality.


My gut [reaction] is to interpret studies like this conservatively. The dramatic differences observed in baseline characteristics in the two study groups suggest that there are quite dramatic unobserved differences that cannot be explained by statistics. The authors had no data on smoking or body mass index, for example.

They did the best they could with what they had, showing that there was a kind of dose-response effect here, with men filling plus Prescriptions for PDE5 inhibitors have a lower risk than those that filled less. And, of course, there really is a biological plausibility to this effect; Remember, PDE5s were initially developed to be antihypertensive and anti-anginal drugs. The effect on erectile dysfunction was a happy accident or perhaps the result of a pharmaceutical executive finding a magic lamp.

And there are others, ahem, mechanisms whereby these drugs may improve long-term results. Without data on sexual activity, we can’t unlink the pharmacological effects of these drugs on blood vessels from their effect on, well, lifestyle. Perhaps these men had more to live for. Several studies, yes, observational, have suggested that more sexual activity is associated with a longer life.

I would need a random test to analyze all of this, one that I am sure you will have no trouble recruiting. Meanwhile, the data we do have seems to suggest that with PDE5 inhibitors, you may get more than you bargained for. Just remember, if your life is longer than 4 hours, call your doctor.

F. Perry Wilson, MD, MSCE, is associate professor of medicine and director of the Yale Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.

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