This transcript has been edited for clarity.
Welcome to Impact factor, weekly dose of comments on a new medical study. I’m Dr. F. Perry Wilson of Yale School of Medicine.
Okay, 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 Journal of the American College of Cardiology.
I know, you think I’m going to be immature about it – jokes, bad puns, that sort of thing. Well, I’m sorry to disappoint you, but this is a serious comment about a serious study.
Briefly, the researchers found a vas deferens between men treated with phosphodiesterase-5 (PDE5) inhibitors, such as Viagra, and those treated with alprostadil.
Okay, I’m sorry. I’m ready now.
The context here is that it has long been established that ED is associated with poor cardiovascular outcomes, probably because it is a proxy for vascular disease. Previous studies in men with ED found that those who received PDE5 inhibitors had lower rates of these negative results than men who did not receive these drugs. But comparing men who receive ED prescriptions with those who do not could introduce prejudice. Men who receive these recipes are healthy enough for sexual activity, for example.
A better control group could be men with ED who receive another type of treatment, such as alprostadil, which is applied topically (by injection, a cream or a urethral suppository).
The study comes from Sweden, where excellent pharmacopepidemiology is located, thanks to their nationwide healthcare database, which includes a huge amount of data on health status, medicines and results for everyone in the country.
The researchers identified about 240,000 Swedish men who had previously had a heart attack or revascularization. Of this group, about 20,000 were receiving ED drugs – mostly PDE5 inhibitors, but enough on alprostadil to do the test.
Top results: Men who took PDE5 inhibitors for ED were much less likely to have MI, coronary revascularization, or heart failure than those who took alprostadil. In fact, up to 15 years of follow-up, 14% of men died of any cause in the PDE5 group, compared with 26% in the alprostadil group.
Of course, when you see results like this, you immediately think of confusion. Who are these men who use injections when there is a pill on the market that gets the same effect? You can see here that the populations were dramatically different. Men treated with alprostadil were more likely to have diabetes, COPD, stroke and active cancer, and were virtually sicker in any way that researchers could measure.
Adjustment 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 cardiovascular mortality rates and all causes.
My gut [reaction] is to interpret studies like this conservatively. The dramatic differences observed in the baseline characteristics in the two study groups suggest that there are rather unnoticed dramatic differences, which could not be taken into account by statistics. The authors did not have data on smoking status or body mass index, for example.
They did their best with what they had, showing that there was some dose-response effect here, with men filling up. More Prescriptions with PDE5 inhibitors have a lower risk than those that filled less. And, of course, there is really biological plausibility for this effect; Remember, PDE5 was originally developed to be antihypertensive and antianginal drugs. The effect on ED was either a happy accident or perhaps the result of a pharmaceutical director who found a magic lamp.
And there are, ahem, mechanisms through which these drugs could improve long-term results. Without data on sexual activity, we cannot unravel the pharmacological effects of these drugs on blood vessels from their effect on lifestyle. Maybe these men had more to live for. Several studies – yes, observational – have suggested that more sexual activity is associated with a longer life.
You would need a randomized study to destroy all of this, one that I am sure will not have problems with recruitment. In the meantime, the data we have suggests that, with PDE5 inhibitors, you may get more than you negotiated. Just remember, if your life is extended by more than 4 hours, call your doctor.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His scientific communication work can be found in the Huffington Post, on NPR and here on Medscape. He sends a tweet @fperrywilson and hosts a repository of his communication works at www.methodsman.com.
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