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Men wouldn't return the trial pills
The failed angina drug
The drug did very little for chest pain. It became Viagra, or sildenafil.
Why it works elsewhere
It works on certain enzymes that are much more common in the lungs and the penis than in the heart or near the heart. That is also why it has a second medical use, treating pulmonary hypertension, where it reduces blood pressure.
The Alzheimer's question
Viagra has also been discussed in the context of Alzheimer's, though no big trial has tested it. So many people now take the drug that looking back at their data could show whether an effect exists.
How does sildenafil work in lungs and penis?
Sildenafil blocks an enzyme called PDE5, which breaks down a chemical messenger, cGMP, that relaxes smooth muscle. With less breakdown, blood vessel walls stay relaxed and widen. PDE5 is abundant in the blood vessels of the penis and the lungs. The FDA approved sildenafil for pulmonary arterial hypertension in 2005 under the name Revatio.
Why test sildenafil on angina first?
Pfizer scientists at Sandwich, Kent, developed it in the late 1980s and early 1990s as a heart drug. The nitric oxide pathway raises cGMP and relaxes the blood vessels that feed the heart, and Pfizer hoped that blocking cGMP's breakdown would ease angina. Trials found little effect on chest pain. The FDA approved sildenafil as Viagra in March 1998.
Why would insurance records hint at Alzheimer's?
Large claims databases show which patients filled prescriptions and who later developed disease. A 2021 analysis in Nature Aging, led by Feixiong Cheng at the Cleveland Clinic, found that sildenafil users had a 69 percent lower likelihood of an Alzheimer's diagnosis than nonusers. The study was observational, so it shows an association and not a proven benefit. The data came from insurance claims covering more than seven million people.
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