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PDE5 inhibition may better improve survival, stable CAD and alprostadil results

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March 22, 2021

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Disclosure: Anderson reports that it was funded by an agreement between the Stockholm County Council and the Karolinska Institute. See the survey for relevant financial disclosures of all other authors. Mars and Rodionov have not reported disclosure of relevant financial information.

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In a comparison of the two erectile dysfunction drugs in men with stable CAD, phosphodiesterase type 5, or PDE5, the researchers reported that the inhibitor was associated with better survival and outcome compared to alprostadil.

According to the data published in journal The·f tHe is an American college The·f Cardiology,male Previous MI or revascularization Compared to alprostadil, treatment with PDE5 inhibitors resulted in lower mortality and lower risk of hospitalization for MI or HF.

In a comparison of the two erectile dysfunction drugs in men with stable CAD, phosphodiesterase type 5, or PDE5, the inhibitor was associated with better survival and outcome compared to alprostadil. The data was obtained from Andersson DP et al. J Am Coll Cardiol.. 2021; doi: 10.1016 /j.jacc.2021.01.045.

“Men treated with PDE5 inhibitors have a lower long-term risk of all causes and cardiovascular death, MI, heart failure, and revascularization after adjusting for potential confounding factors such as marital status and duration of education. Was Daniel P. Anderson, MD, PhDWritten by a colleague of the Karolinska Institute School of Medicine at the Karolinska University Hospital in Stockholm. “As far as we know, this is the largest study investigating the association between erectile dysfunction drug use and long-term outcomes.”

In this study, researchers began all treatments for erectile dysfunction with PDE5 inhibitors or alprostadil more than 6 months after the index event in Swedish patient enrollments and Swedish prescription drug enrollments with a history of MI or revascularization. Men were included (16,548 people treated with PDE5; 1,994 treated with alprostadil).

“Erectile dysfunction is a common multifactorial condition that affects more than 40% of men over the age of 70,” the researchers write. “It is associated with an increased risk of cardiovascular events and mortality with the general public. Individuals with established cardiovascular disease.. “

PDE5 Inhibition vs. Alprostadil

During an average follow-up of 5.8 years, 26% of Alprostadil participants and 14% of PDE5 inhibitors died to treat erectile dysfunction.

Researchers have observed that men who have previously undergone MI or revascularization have a 12% lower risk of death when treated with PDE5 inhibitors than men who receive alprostadil (” Adjusted HR = 0.88; 95% CI, 0.79-0.98).

Inhibition of PDE5 for erectile dysfunction is also associated with a 19% lower risk of MI (aHR = 0.81; 95% CI, 0.7-0.93) and a 25% lower risk of HF hospitalization compared to alprostadil. (AHR = 0.75; 95% CI, 0.64-0.88).

Treatment with PDE5 inhibition compared to alprostadil only affected CV-related mortality (CV mortality aHR = 0.83; 95% CI, 0.7-0.98; non-CV mortality aHR = 0.92; 95 % CI, 0.79-1.07). Survey.

“This suggests a causal relationship, but a registry survey cannot answer that question.” Martin Holtzmann, MD, PhD, A part-time professor of medicine at the Karolinska Institute, said in a press release. “Patients who received PDE5 inhibitors were healthier than those who received alprostadil, so they may have been at lower risk. To see if the drug reduces the risk, Patients should be randomly assigned to two groups, one taking PDE5 and the other not. The results we now have are a very good reason to undertake such a study. Give us. “

Number of prescriptions filled and mortality

Compared to the lowest quintile of the filled PDE5 inhibitor prescription, the three highest quintile men experienced significant benefits to reduce mortality (3 quintiles aHR = 0.84; 95). % CI, 0.74-0.96; aHR in quintile 4 = 0.75; 95% CI, 0.66-0.85; aHR in quintile 5 = 0.73; 95% CI, 0.63-0.84). Similar observations were made for men in the lowest quintile of the filled alprostadil prescription compared to the highest.

However, the reduction in CV mortality is associated only with the 4th quintile of PDE5 inhibitor users and the 5th quintile of alprostadil users, compared to their lowest quintiles in the prescription. There was no association between the quintile and changes in MI and HF hospitalization.

“The association between PDE5 inhibitor use and survival observed in men with coronary artery disease is interesting, but still insufficient to support changes in clinical practice.” Renke Mars, MDThe Institute of Experimental and Clinical Pharmacology and Toxicology, Erlangen-Nuremberg, Friedrich-Alexander University, Erlangen, Germany, and Roman numerals Rodionov, MD, PhDThe Department of Angiology, Department of Internal Medicine, Dresden University of Technology, Dresden University of Technology, wrote in a related editorial.

“The problem of confounding and bias due to indications can only be solved by a randomized, placebo-controlled trial,” the editors write. “But before we start such a trial, we must first address one question. The pharmaceutical industry has not conducted any larger trials in this wide range of indications in the last 20 years. Why? Consider that sufficient data showing beneficial effects in the cardiovascular system and that PDE5 inhibitors were originally developed in the 1990s with the enormous potential market for coronary artery disease and hypertension in mind. And this is puzzling. The answer may provide some important, and perhaps cool, insights. “

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