ED Medication Tadalafil Significantly Lowers Risk of Major Adverse Cardiovascular Events, Study Finds

Erectile dysfunction (ED) medications appear to include a bonus benefit: a healthier heart. Multiple studies have indicated that PDE5 inhibitors, a class of drugs that includes well-known brands Viagra®, Cialis®, and Stendra®, may reduce a patient’s risk of experiencing major adverse cardiovascular events (MACE) like heart attacks or strokes.

Experts are building on this research with a first-of-its-kind study focused on tadalafil (also sold under the brand name Cialis), a long-acting PDE5 inhibitor that can be taken daily or as needed to treat ED. In addition to providing further evidence that ED medications can boost heart health, the study published in Clinical Cardiology also points to a link between dosage levels and patient outcomes.

The purpose of the observational study was to analyze whether prolonged exposure to a PDE5 inhibitor leads to improved cardiovascular outcomes. Tadalafil is unique as an ED drug because it’s a long-acting agent that remains in the system for up to 36 hours, which is far longer than comparable medications like Viagra (learn more about the differences between Cialis and Viagra here). Tadalafil is also FDA-approved for daily use.

Researchers retrospectively analyzed data from a large U.S. commercial insurance claims database and compared the information to the national death index. They identified adult men diagnosed with erectile dysfunction between January 2006 and October 2020. 

The researchers divided the men into two groups: The first included more than 8,000 men who started using tadalafil after receiving their diagnosis and had not experienced MACE in the 12 months before beginning the drug. The second group comprised more than 21,000 men diagnosed with ED who did not take tadalafil or any other PDE5 inhibitor. 

The analysis revealed the men who took tadalafil fared better than the ones without exposure to the drug. Compared to the men who didn’t take any PDE5 inhibitors, the men exposed to tadalafil had:

• 19% lower adjusted rates of MACE, including significantly lower rates of coronary revascularization and unstable angina

• 44% lower mortality rates

Dosage levels also contributed to patient outcomes. The men who took tadalafil were subdivided based on the number of tablets prescribed during the analysis period. The data revealed that higher dosages correlated with lower MACE and mortality rates.

Peter Stahl, MD, a urologist who prescribes tadalafil to his patients but was not involved in the new study, says the results make sense. “It’s reasonable to think that exposure to tadalafil, which is active for longer periods per dose compared to other drugs, might be more cardioprotective.”

The tadalafil study expands and builds upon previous research on the potential benefits of PDE5 inhibitors. A report published in December 2023 by the Princeton Consensus Conference analyzed at least 10 studies on PDE5 inhibitors conducted between 2016 and 2023. Each study concluded the medications were safe, and the majority found that PDE5 inhibitors were associated with lower rates of cardiovascular events and deaths.

The Princeton report also highlights a correlation between higher dosage levels and lower rates of MACE and stroke—just like the new study on tadalafil. Dr. Stahl, who is the senior vice president of Men’s Sexual Health & Urology at Hims & Hers, says this detail is important when evaluating the effectiveness of tadalafil and other ED treatments. 

“People with heart disease and ED who are still healthy enough to have sex are probably the ones taking the drugs. And people who are too sick to have sex are likely not taking ED drugs,” explains Dr. Stahl, “so the PDE5 inhibitor and decreased MACE association could be driven by selection bias.”

That higher dosage levels have been linked to better health outcomes is “compelling,” Dr. Stahl continues. “The dose-response relationship challenges the idea that it’s just selection bias because if anything, the people that need higher doses are the ones with worse ED, who you’d expect to have more serious underlying vascular problems. The fact that the more exposure you have to the drug, the more you're protected you are, is reassuring.” 

As Dr. Stahl and the study’s authors pointed out, one of the weaknesses of this study and others like it is the retrospective approach. Researchers analyzed existing data but had no oversight over the participants, and it’s always possible that unknown variables contributed to the results. In the tadalafil study, the researchers also did not directly compare the drug against short-acting PDE5 inhibitors.

Dr. Stahl explains that the existing research on the benefits of tadalafil and other PDE5 inhibitors for heart health “don’t imply causality just yet because that’s a pretty high bar. But these are high-powered, well-done, well-designed, population-based, observational studies that all show the same thing,” he says.

“At some point, the weight of the preponderance of all the evidence makes you start thinking about causality. It's at least becoming extraordinarily clear that these drugs are safe from a cardiovascular standpoint.”