Sildenafil is the generic name for Viagra, the popular drug for treating erectile dysfunction in men. Although it may not be widely known, sildenafil was actually first synthesized as part of a cardiovascular research program. Studies that were undertaken to test the drug’s effects on cardiovascular conditions showed that some patients reported a side effect of increased penile erections. Not long after this discovery, clinical trials were undertaken to study the drug’s effects on ED. Now, researchers are returning to the cardiovascular effects of PDE-5 inhibitors to see if they are having some additional health benefits for men who take them.
Sildenafil History
As mentioned, sildenafil was discovered as part of a program to find new treatments for cardiovascular conditions. When the side effect of increased erections was discovered, it was not long after put into clinical trials for erectile dysfunction. After thousands of men were given the drug for ED and efficacy was consistently demonstrated in clinical trials, it was approved by the FDA in 1998. Within weeks, more than a million prescriptions were written for the drug. In that time, the cardiovascular benefits of the drug have not been ignored by researchers but have not been apparent to the general public either. Is it possible that men who take PDE-5 inhibitors like sildenafil and tadalafil also have improved cardiac functioning compared to men who do not take them?
New Journal of Sexual Medicine Study
A new study in the Journal of Sexual Medicine expands on the current research. This retrospective observational cohort study included a large group of 23,816 men who had ED and were prescribed PDE-5 inhibitors. It included a control group of 48,682 men without PDE-5 inhibitor exposure. The use of PDE-5 inhibitors was associated with reduced major adverse cardiovascular events (MACE) and mortality in a large general US population of men with ED. Exposure to PDE-5 inhibitors was associated with significant and clinically meaningful lower incidence of MACE (by 13%), total mortality (by 25%) and CV mortality (by 39%), compared to the matched control group without exposure to PDE-5 inhibitors.
Recent studies have shown that there are no significant increases in adverse events when PDE-5 inhibitors are combined with nitrates. Another study published in the Journal of Sexual Medicine demonstrated that being prescribed both types of medications did not necessarily increase cardiovascular risks, although researchers noted that that co-exposure to both should still be avoided.
The results of the new study also confirm other recent studies that show the use of tadalafil in patients with diabetic cardiomyopathy improves cardiac function. Tadalafil is similar to sildenafil but is often prescribed to be taken daily instead of as-needed. Taking tadalafil daily has a cumulative effect that allows more spontaneity in sexual activity. Several studies have already shown that it is safe and effective for men with diabetes.
One of the theories as to why this class of drugs can help heart conditions is that they improve the dilation of blood vessels and result in a slight decline in blood pressure. Over time, this may reduce the amount of work done by the heart and prevent atherosclerosis (plaque buildup in arteries). Some studies have shown additional cardioprotective effects like preventing blood clots and reducing inflammation.
Limitations of the Study
One limitation of the study is that it is possible that men who take ED medications and engage in sexual activity are healthier than men who do not. The study also did not independently measure men who engaged in sexual activity but without a pharmacological intervention. In addition, the study used a population of men who had been prescribed PDE-5 inhibitors but there was no data on how compliant they were with their treatment or if they were actually taking them. Many men are prescribed sildenafil and take it “as-needed” not on a regular basis. Further randomized, placebo-controlled clinical trials should be conducted to confirm that PDE-5 inhibitors have cardioprotective effects.
Articles
Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond – Nature Public Health Emergency Collection
Effect of phosphodiesterase type 5 inhibitors on major adverse cardiovascular events and overall mortality in a large nationwide cohort of men with erectile dysfunction and cardiovascular risk factors: A retrospective, observational study based on healthcare claims and national death index data – The Journal of Sexual Medicine
Cardiovascular Outcome Risks in Patients With Erectile Dysfunction Co-Prescribed a Phosphodiesterase Type 5 Inhibitor (PDE5i) and a Nitrate: A Retrospective Observational Study Using Electronic Health Record Data in the United States – The Journal of Sexual Medicine