This transcript has been edited for clarity.
Welcome to Impact factor, your weekly dose of comments on a new medical study. I’m Dr. F. Perry Wilson, from the Yale School of Medicine.
Okay, let’s get something out of the way. This week, we’re talking about drugs for erectile dysfunction (ED) and long-term mortality, thanks to this study, which appear in the Journal of the American College of Cardiology.
I know, you think I’m going to be immature about it – jokes, puns, that kind of thing. Well, I’m sorry to disappoint you, but this is a serious comment about serious study.
Briefly, the researchers found a different channel between men treated with phosphodiesterase-5 (PDE5) inhibitors, such as Viagra, and those treated with alprostadil.
OK sorry. I’m done now.
The background here is that it has long been established that ED is associated with poor cardiovascular outcomes, probably because it is a substitute for vascular disease. Previous studies of men with erectile dysfunction found that those who received PDE5 inhibitors had lower rates of poor results than men who did not receive these drugs. But comparing men who receive ED prescriptions with those who don’t can be prejudiced. The men who receive these recipes are healthy enough for sexual activity, for example.
A better control group may be men with erectile dysfunction receiving another type of treatment, such as alprostadil, which is applied locally (via injection, cream or urethral suppository).
The study comes from Sweden, home to an excellent pharmacoepidemiology, thanks to its national health database that includes a large amount of data on the state of health, medicines and results of everyone in the country.
The researchers identified about 240,000 Swedish men who had a previous myocardial infarction or revascularization. Of that group, about 20,000 were receiving ED medication – mainly PDE5 inhibitors, but enough with alprostadil to do the analysis.
Top line results: Men taking PDE5 inhibitors for ED were much less likely to have myocardial infarction, coronary revascularization or heart failure than those taking alprostadil. In fact, over 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 has 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 were basically more ill in any way that the researchers could measure.
Adjusting for all of these factors dramatically mitigated 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 in a conservative way. The dramatic differences observed in the baseline characteristics in the two study groups suggest that there are quite dramatic differences not observed that could not be explained by statistics. The authors had no data on smoking or body mass index, for example.
They did their best with what they had, showing that there was something like a dose-response effect here, with men filling in most The prescriptions for the PDE5 inhibitor are less risky than those that filled it less. And, of course, there really is biological plausibility for that purpose; remember that PDE5s were initially developed to be antihypertensive and anti-anginal drugs. The effect on ED was a happy accident or perhaps the result of a pharmaceutical executive finding a magic lamp.
And there are others, ahem, mechanisms why these drugs can improve long-term results. Without data on sexual activity, we cannot separate the pharmacological effects of these drugs on blood vessels from their effects on, say, lifestyle. Perhaps these men had more to live for. Several studies – yes, observational ones – have suggested that more sexual activity is associated with longer life.
You would need a randomized trial to separate all of this, one that I am sure will have no problems with recruitment. In the meantime, the data we have seems to suggest that, with PDE5 inhibitors, you may be getting more than you expected. Just remember, if your life spans more 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 on the Huffington Post, on the NPR and here on Medscape. He tweets @fperrywilson and hosts a repository of your communication work at www.methodsman.com.
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