Risk for death, heart events rises when combining erectile dysfunction drugs, nitrates
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Key takeaways:
- Men with CAD who combined nitrates with common ED drugs were at higher risk for death and adverse CV events.
- The risk for adverse events was low during the first 28 days after filling an ED drug prescription.
Men with CAD taking nitrates for chest pain plus a PDE5 inhibitor for erectile dysfunction were at greater risk for death or major adverse CV events compared with men taking nitrates alone, Swedish registry data show.
“Patients with stable CAD using nitrate medication who also use the most common treatment for erectile dysfunction (ED) need to consider the benefits of PDE5 inhibitors against the possible cardiovascular risk,” Ylva Trolle Lagerros, MD, PhD, associate professor at the Karolinska Institutet and a senior physician at the Center for Obesity, Stockholm, told Healio. “It is advisable to exercise careful, patient-centered consideration before prescribing PDE5 inhibitors to people with stable CAD who are using nitrate medication and weigh the benefits of the medication against the possible increased risk for cardiovascular morbidity and mortality given by this combination.”
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Impact of ED drugs with nitrates
Lagerros and colleagues analyzed data from 55,777 men with a history of MI or revascularization from 2006 to 2013 who filled at least two nitrate prescriptions within 6 months, including 5,710 men (9%) who also filled at least two prescriptions for a PDE5 inhibitor within 6 months, using the Swedish Patient Register and the Prescribed Drug Register. The median age was 70 years for men prescribed nitrates only and 61 years for men prescribed nitrates plus a PDE5 inhibitor.
“Based on the uncertainty of when the patients really take their PDE5 inhibitor, we considered the patients to be exposed during the whole follow-up period following dispensation of PDE5 inhibitor from the pharmacy,” the researchers wrote. “However, to be certain that the patients really used their PDE5 inhibitor and not only collected it from the pharmacy once, exposure was defined as prescriptions of PDE5 inhibitors dispensed on two different occasions. With two dispensed prescriptions, the person was considered to be exposed to PDE5 inhibitors from the time of the first dispensed prescription.”
Researchers calculated HRs for all-cause mortality, CV mortality, non-CV mortality, MI, HF, cardiac revascularization and major adverse CV events.
The findings were published in the Journal of the American College of Cardiology.
Within the cohort, the combined use of PDE5 inhibitor treatment with nitrates was associated with higher mortality (HR = 1.39; 95% CI, 1.28-1.51), CV mortality (HR = 1.34; 95% CI, 1.11-1.62), non-CV mortality (HR = 1.4; 95% CI, 1.27-1.54), MI (HR = 1.72; 95% CI, 1.55-1.9), HF (HR = 1.67; 95% CI, 1.48-1.9), cardiac revascularization (HR = 1.95; 95% CI, 1.78-2.13) and major adverse CV events (HR = 1.7; 95% CI, 1.58-1.83) compared with nitrates alone.
In a secondary analysis that defined exposure as 28 days after a PDE5 inhibitor dispensation, the researchers observed low incidence rates and few events among men prescribed both nitrates and PDE5 inhibitors. HRs ranged from 0 to 0.37 with 95% CIs ranging from zero to 0.85. In this analysis, the incidence rate for all-cause mortality was lower among men taking nitrates and PDE5 inhibitors vs. those taking nitrates only (0.4 vs. 6.73 cases per 100 person-years).
“A register-based observational study such as this one can give us the associations, but we cannot infer causality from the results,” Lagerros told Healio. “However, the random assignment in a randomized controlled trial, for example, could help to minimize known and unknown confounders.”
ED, CAD ‘unfortunate bedfellows’
In a related editorial published in the Journal of the American College of Cardiology, Glenn N. Levine, MD, FAHA, master clinician and professor of medicine at Baylor College of Medicine and chief of the cardiology section at the Michael E. DeBakey VA Medical Center, wrote that clinicians must counsel patients prescribed nitrates for chest pain who take ED drugs to call 911 if angina develops during sexual intercourse and does not resolve upon cessation of sexual activity, adding that it is also important to make medical personnel aware that a person taking nitrates recently used a PDE5 inhibitor.
“ED and CAD are unfortunate, and all too common, bedfellows,” Levine wrote. “But, as with most relationships, assuming proper precautions and care, they can coexist together for many years, perhaps even a lifetime.”
Reference:
For more information:
Ylva Trolle Lagerros, MD, PhD, can be reached at ylva.trolle@ki.se; X (Twitter): @karolinskainst.
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