The use of a phosphodiesterase type-5 (PDE5) inhibitor was associated with a lower risk for death and cardiovascular events than alprostadil for the treatment of erectile dysfunction in men with stable coronary artery disease in a large Swedish enrollment study.
“We decided to look at this group as incapacity is a major problem among older males,” and there are still concerns about whether PDE5 protectors can be used in those in this group. also have cardiovascular disease, “lead author Daniel P. Andersson, MD, PhD, Karolinska Institute, Stockholm, Sweden, said in an interview.
The team previously reported a mortality benefit of PDE5 inhibitors in men with the first myocardial infarction (MI), as did a British study in men with type 2 diabetes. However, the two compared between treatment with men who were not taking erectile dysfunction (ED) drugs, which may have been accompanied by symptomatic upset, he noted.
The current analysis included 18,542 Swedish men with ED who had MI or underwent coronary bypass surgery or percutaneous coronary intervention, of which 16,548 were treated with a PDE5 inhibitor (sildenafil, tadalafil, or vardenafil) and 1994 with local alprostadil. The average follow-up period for mortality was 5.8 years.
Alprostadil users were more likely to have a previous stroke, diabetes, active cancer, heart failure, chronic obstructive pulmonary disease, atrial fibrillation, or use peripheral artery disease and beta blockers, turned-on enzyme inhibitors angiotensin / angiotensin inhibitors, thiazides, opioids, nitrates, or selective serotonin reuptake inhibitors. PDE5 inhibitor users were slightly younger and more likely to receive postgraduate education.
After controlling these factors, the modified risks in the PDE5 inhibitor group were:
-
12% lower for all-cause mortality (14% vs. 26%; risk ratio) [HR], 0.88)
-
19% lower for myocardial infarction (9.4% versus 15%; HR, 0.81)
-
25% lower for heart failure hospitals (1.0% vs. 2.1%; HR, 0.75)
-
31% lower for recovery (13.1% vs 21%; HR, 0.69)
The modified risks for stroke and peripheral artery disease were similar between the two treatment groups, according to the study, published March 22 in the Journal of the American College of Geology.
Rates of cardiovascular (5.1% vs 10.6%) and noncardiovascular (6.9% vs 12.2%) mortality were significantly reduced in the PDE5 inhibitor group, although the association with treatment was significant after adjustment only for cardiovascular death (HR, 0.83) and not for noncardiovascular death.
“Our first idea was that cardiovascular mortality would be reduced but, as we can see, non-biological mortality was also reduced and we did not expect that,” Andersson said. leading to reduced mortality, but we cannot yet say anything about causation. “
Age-based analyzes indicated that men aged 60 to 69 years treated with PDE5 inhibition had lower mortality than their alprostadil-treated peers (modified HR, 0.81). This has not been seen, however, for men older than 70 years.
When the researchers compared quintiles of filled PDE5 protective orders, men in the third, fourth, and fifth quintiles had a 16%, 25%, and 27% lower risk of change, compared to men in the reed lowest. Men in the top fifth of alprostadil prescriptions had a lower risk of death compared to those in the bottom fifth.
“We need randomized controlled trials, however, if the doctor prescribing this medication sees that you are fit enough to get it, it is very likely to be good for you and you can take it with you and feel safe about it, “Andersson said.
Renke Maas, MD, Friedrich University Alexander Erlangen-Nürnberg, Erlangen Germany, and Roman Rodionov, MD, PhD, Dresden University of Technology, Dresden, Germany, write in an accompanying editorial “that the observed association of PDE5i use and survival in men with coronary artery disease is interesting but still sufficient to support any change in clinical use. “
They indicate that PDE5 or alprostadil inhibitors are not usually prescribed or given for daily use and that only tadalafil once a day, with an action period of 24 to 36 hours, would not meet the criteria for continued publication. “This makes it difficult to assign any strong association with mortality to normal dosing patterns of PDE5i in men with ED.”
“Supporting a causal relationship, it could be argued that PDE5i in the Swedish cohort, with a high incidence of hip hypertension, may have survived by contributing to the clinical effects of antihypertensive drugs,” they write. “Many may like the notion that sex is often certified as a lifelong stimulating physical activity and that PDE5i may reverse this benefit in fear of ED. Unfortunately, this interpretation could be a cause for action. “
General health decline is associated with a decrease in sexual desire and activity and, therefore, high harmful exposure to PDE5 inhibitors may have just identified healthier and more active patients, Maas and Rodionov suggest .
The editors agree that a randomized controlled trial is needed to deal with controversial and discriminatory cases with a mark but say that before such a trial begins, “one question should be addressed first: Why Hasn’t the pharmaceutical industry done more general testing of this brand in the last 20 years?
“This is disappointing, considering the ample experimental data showing beneficial effects in the cardiovascular system and that PDE5i was originally developed in the 1990s with the potentially huge markets. in prospective coronary artery and hip artery disease, ”they add. “
The study was conducted in collaboration with the Obesity Center in Stockholm, Sweden, and the University of Milan-Bicocca in Italy. Andersson was funded by a regional agreement on medical training and clinical research between Stockholm County Council and the Karolinska Institutet. Maas and Rodionov did not disclose any material financial relationships.
J Am Coll Cardiol. 2021; 77; 1535-1550, 1551-1553. Full text, Editorial
Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Epistemology, join us on it Twitter and Facebook.