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 of the 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’ll be immature with that: jokes, sad puns, that sort of thing. Well, I’m sorry to disappoint you, but this is a serious comment on 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, sorry. I have finished.
The background here is that ED has long been established to be associated with poor cardiovascular outcomes, probably because it is a substitute for vascular disease. Previous studies in men with ED found that those who received PDE5 inhibitors had lower rates of these poor outcomes than men who did not receive these drugs. But comparing men who receive ED prescriptions with those who do not can introduce bias. Men who receive these recipes are, for example, healthy enough for sexual activity.
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, home to a large pharmacoepidemiology, thanks to its nationwide health database that includes a wealth of data on health status, medications, and outcomes from everyone in the country.
The researchers identified about 240,000 Swedish men who had a myocardial infarction or previous revascularization. Of this group, about 20,000 received ED drugs, mainly PDE5 inhibitors, but enough alprostadil to do the analysis.
Main results: Men taking PDE5 inhibitors for ED were much less likely to have MI, 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 with 26% in the alprostadil group.
Of course, when you see results like this, you will immediately think of confusing. Who are these men who make 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 with alprostadil were more likely to have diabetes, COPD, stroke, and active cancer, and were basically sicker in any way that researchers could measure.
The adjustment of all these factors drastically attenuated the observed benefit of PDE5 inhibitors, but did not eliminate it. The class was still associated with lower cardiovascular and all-cause mortality rates.
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 rather dramatic unobserved differences that statistics could not account for. The authors had no data on smoking status or body mass index, for example.
They did their best with what they had, proving that there was something of a dose-response effect here, with men filling up. month PDE5 inhibitor prescriptions have a lower risk than those that filled less. And, of course, there is really biological plausibility to this effect; remember that PDE5s were initially developed to be antihypertensive and antianginal drugs. The effect on ED was a happy accident or perhaps the result of a pharmaceutical executive who found a magic lamp.
And there are others, mechanisms whereby these drugs could improve long-term outcomes. Without data on sexual activity, we cannot disassociate the pharmacological effects of these drugs on blood vessels from their effect on good, lifestyle. Maybe these men had more to live on. Several (yes, observational) studies have suggested that more sexual activity is associated with a longer life.
You will need a random trial to separate all of this, which I am sure you will have no problems with hiring. Meanwhile, the data we have suggests that, with PDE5 inhibitors, you could get more than you traded. Remember that if your life is longer than 4 hours, call your doctor.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of the Yale Clinical and Translational Research Accelerator. His scientific communication work can be found in the Huffington Post, NPR and here at Medscape. Make a tweet @fperrywilson and hosts a repository of his communication work at www.methodsman.com.
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