PDE5 inhibition may better improve survival, outcomes in stable CAD vs. alprostadil
Click Here to Manage Email Alerts
In a comparison of two erectile dysfunction medications in men with stable CAD, phosphodiesterase type 5, or PDE5, inhibitors were associated with better survival and outcomes compared with alprostadil, researchers reported.
According to data published in Journal of the American College of Cardiology, men with prior MI or revascularization experienced lower mortality and risk for MI or HF hospitalization when treated with PDE5 inhibitors compared with alprostadil.
“Men with PDE5 inhibitor treatment had lower long-term risk of all-cause and cardiovascular mortality, MI, heart failure and cardiac revascularization after adjustment for potential confounders, including marital status and length of education,” Daniel P. Andersson, MD, PhD, of the department of medicine at the Karolinska Institutet, Karolinska University Hospital in Stockholm, and colleagues wrote. “To our knowledge, this is the largest study investigating the association between the use of erectile dysfunction medication and long-term outcomes.”
For this study, researchers included all men in the Swedish Patient Register and the Swedish Prescribed Drug Register with prior MI or revascularization who started treatment for erectile dysfunction with a PDE5 inhibitor or alprostadil more than 6 months after their index event (16,548 treated with PDE5; 1,994 treated with alprostadil).
“Erectile dysfunction is a multifactorial and common condition affecting more than 40% of men older than 70 years,” the researchers wrote. “It is associated with an increased risk of cardiovascular events and mortality in the general population and among individuals with established cardio-vascular disease.”
PDE5 inhibition vs. alprostadil
During a mean follow-up of 5.8 years, 26% of participants on alprostadil to treat erectile dysfunction and 14% on PDE5 inhibitors died.
Researchers observed that men with prior MI or revascularization treated with PDE5 inhibitors had a 12% lower risk for mortality compared with those on alprostadil (adjusted HR = 0.88; 95% CI, 0.79-0.98).
PDE5 inhibition for erectile dysfunction was also associated with a 19% lower risk for MI (aHR = 0.81; 95% CI, 0.7-0.93) and a 25% lower risk for HF hospitalizations compared with alprostadil (aHR = 0.75; 95% CI, 0.64-0.88).
Treatment with PDE5 inhibition compared with alprostadil only affected CV-related mortality (aHR for CV mortality = 0.83; 95% CI, 0.7-0.98; aHR for non-CV mortality = 0.92; 95% CI, 0.79-1.07), according to the study.
“This suggests that there’s a causal relationship, but a registry study can’t answer that question,” Martin Holzmann, MD, PhD, adjunct professor in the department of medicine at Karolinska Institutet, said in a press release. “It is possible that those who received PDE5 inhibitors were healthier than those on alprostadil and therefore had a lower risk. To ascertain whether it is the drug that reduces the risk, we would need to randomly assign patients to two groups, one that takes PDE5 and one that doesn’t. The results we have now give us very good reason to embark on such a study.”
Number of filled prescriptions and mortality
Compared with the lowest quintile of filled PDE5 inhibitor prescriptions, men in the three highest quintiles experienced significant benefit for reducing mortality (aHR for quintile 3 = 0.84; 95% CI, 0.74-0.96; aHR for quintile 4 = 0.75; 95% CI, 0.66-0.85; aHR for quintile 5 = 0.73; 95% CI, 0.63-0.84). A similar observation was made for men in the lowest quintile of filled alprostadil prescriptions compared with the highest.
However, reduced CV mortality was only associated with the fourth quintile among PDE5 inhibitor users and fifth quintile among alprostadil users, compared with the lowest quintiles of each, and no association between quintiles of prescriptions filled and changes in MI and HF hospitalization.
“The observed association of PDE5 inhibitor use and survival in men with coronary artery disease is intriguing but still insufficient to support any change in clinical practice,” Renke Maas, MD, of the Institute of Experimental and Clinical Pharmacology and Toxicology at Friedrich-Alexander-Universität Erlangen-Nürnberg in Erlangen, Germany, and Roman N. Rodionov, MD, PhD, of the division of angiology in the department of internal medicine at the University Center for Vascular Medicine, Technische Universität Dresden, Germany, wrote in a related editorial.
“Issues of confounding and bias by indication can only be resolved by a randomized placebo-controlled trial,” the editorial authors wrote. “However, before initiating such a trial one question should be addressed first: Why has the pharmaceutical industry not already conducted any larger trials in this broad indication in the last 20 years? This is puzzling, considering the ample experimental data indicating beneficial effects in the cardiovascular system and that PDE5 inhibitors were originally developed in the 1990s with the very large potential markets in coronary artery disease and hypertension in mind. The answers may offer some important, and possibly sobering, insights.”
Reference:
Collapse
Click Here to Manage Email Alerts