Nitrates and Erectile Dysfunction Meds? Increasingly Common, Mostly Benign

Despite widely publicized warnings about the potential interaction between nitrates prescribed for angina and oral (phosphodiesterase type 5) PDE5 inhibitors taken for erectile dysfunction, a Danish study suggests that prescriptions for the latter have steadily increased over the last 20 years in men who take nitrates, but without an accompanying increase in adverse CV events.

Current guidelines for the management of patients with unstable angina/NSTEMI state that nitroglycerin or other nitrates should not be administered within 24 hours of taking sildenafil or within 48 hours of tadalafil, two of the most common PDE5 inhibitors.

Anders Holt, MD (Herlev and Gentofte Hospital, Hellerup, Denmark), who led the new study, told TCTMD that his group’s data suggest that “it seems safe to possess both drugs, which could suggest that patients are adequately warned against co-use and that patients follow this recommendation. It could also point towards an increased empowering of patients and focus on quality of life, where patients are involved in the decisions and discussions concerning the worries in relation to co-prescribing.”

For the study, published online ahead of print in Annals of Internal Medicine, Holt and colleagues analyzed registry data on 249,541 male patients with CAD. Of these, 42,073 (median age 70) had prescriptions for nitrates. Overall, there was a 20-fold increase in PDE5 inhibitor prescriptions between 2000 and 2018 in those with nitrate prescriptions and a 10% increase in the overall group of patients with CAD. The majority of PDE5 inhibitor prescriptions—69%—were written for sildenafil.

Looking at all cases of cardiac arrest, shock, MI, ischemic stroke, or angiography during follow-up, there was no evidence of an increased risk of these events during a 14-day window when patients had filled a PDE5 inhibitor prescription compared with a similar time frame when they had only filled a nitrate prescription (OR 0.58; 95% CI 0.28-1.13). There also was no increase in syncope, angina, or drug-related adverse events (OR 0.73; 95% CI 0.40-1.32).

A primary limitation of the study is that Holt and colleagues could not be certain when the nitrates and PDE5 inhibitors were taken in relation to each other, only that patients had prescriptions for both.

It could also point towards an increased empowering of patients and focus on quality of life, where patients are involved in the decisions and discussions concerning the worries in relation to co-prescribing. Anders Holt

Holt and colleagues say that in addition to the possibility that patients are being well-informed about the interaction by their physicians as an explanation for the lack of increased events, there also may be enough of a time window to avoid any interaction if patients are regularly taking their nitrates in the morning but not taking the PDE5 inhibitors until evening. If that is the case, they say, the nitrates could be sufficiently metabolized by late in the day so that any synergistic interaction would be negligible.

A third possibility, however, is that some men do experience hypotension from taking both drugs, but that it isn’t significant enough to seek medical help or to report to a physician. To TCTMD, Holt said men who are experiencing the interaction shouldn’t remain silent about it.

“If hypotensive symptoms arise, I would recommend that patients talk to their physician in order to discuss alternatives or other mitigation strategies,” he said. “Drops in blood pressure which the patient feels for a longer period should be avoided, in my opinion.”