PDE5 inhibitors didn't increase cardiovascular events in men on nitrates for heart disease

A Danish study also found that more men with ischemic heart disease are taking both nitrates and a phosphodiesterase type 5 (PDE5) inhibitor, with the prescription rate increasing 20-fold from 2000 to 2018.

Men with heart disease who took both nitrates and a phosphodiesterase type 5 (PDE5) inhibitor did not have a statistically significant increase in cardiovascular risk, a study found.

Researchers from Denmark collected patient data from the country's health registries to observe trends of coprescription of nitrates and PDE5 inhibitors and to measure any association with cardiovascular outcomes. The nationwide study focused on men with ischemic heart disease (IHD) from 2000 to 2018, including those who had a continuing prescription for nitrates and a new, filled prescription for PDE5 inhibitors. Two composite outcomes were studied: cardiac arrest, shock, myocardial infarction, ischemic stroke, or acute coronary arteriography and syncope, angina pectoris, or drug-related adverse events. The study was published April 19 by Annals of Internal Medicine.

Of 249,541 patients with IHD, 42,073 had continuing prescriptions for nitrates during the study period. The prescription rate for PDE5 inhibitors in patients with IHD who were taking nitrates increased 20-fold from an average of 0.9 prescriptions (95% CI, 0.5 to 1.2) per 100 persons per year in 2000 to 19.5 prescriptions (95% CI, 18.0 to 21.1 ) in 2018. No statistically significant association was found between coprescription of nitrates with PDE5 inhibitors and risk for either composite outcome (odds ratios, 0.58 [95% CI, 0.28 to 1.13] for the first outcome and 0.73 [95% CI, 0.40 to 1.32] for the second outcome).

While the study authors do not recommend coprescription of these medications for all patients, they said that a possible explanation for this lack of evidence of adverse events is that doctors are advising patients to take the two drugs at different times of the day, and patients are following this advice.

“… [N]itrates are often taken in the morning, and we think it is a reasonable assumption that most PDE5 inhibitors are taken in the evening. Therefore, for patients who meet these assumptions, the nitrates could be metabolized to a degree such that the synergistic interaction is negligible. Isosorbide dinitrate and isosorbide mononitrate accounted for 78% and 21% of the nitrates in our study and have plasma half-lives of 4.5 and 5 hours, respectively, conceivably allowing for a sufficient reduction in plasma levels,” they wrote.