Erectile Dysfunction Drugs Plus Nitrates Tied to CV Morbidity and Mortality Risk – Renal and Urology News

Among men with stable coronary artery disease (CAD), the use of phosphodiesterase-5 inhibitors (PDE5is), or erectile dysfunction drugs, combined with nitrate medication may increase the risk for cardiovascular morbidity and mortality, according to study findings published in the Journal of the American College of Cardiology.

Erectile dysfunction is typically treated with PDE5is by causing hypotension. Nitrates also cause hypotension and are therefore contraindicated in combination. However, given results from previous studies, researchers from the Karolinska Institutet in Stockholm, Sweden hypothesized that PDE5i would be associated with improved survival and cardiovascular morbidity among patients with CAD on nitrates.

To test their hypothesis, the researchers sourced data for this study from the National Swedish Patient Registry which includes data from all hospital stays in Sweden since 1987. Men (N=61,487; mean age, 69.5) who had undergone revascularization or had a myocardial infarction (MI) between 2006 and 2013 and had 2 dispensed nitrate prescriptions within 6 months were evaluated for mortality on the basis of filling 2 or more prescriptions of any PDE5i. Major cardiovascular events (MACE) was defined as heart failure, MI, or cardiac revascularization.

Of the study participants:

• 22.6% had diabetes,
• 10.4% had a history of stroke,
• 94.6% were using platelet inhibitors,
• 87.5% b-blockers,
• 84.4% statins, and
• 73.5% angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

Overall, 9% of men were exposed to PDE5is. The men who used nitrates and PDE5i were younger (mean age, 61.2) than those who used only nitrates (mean age, 70.3).

Overall, mortality occurred among 43% of the nitrate group compared with 10.4% of the nitrate and PDE5i group. Exposure to PDE5i was associated with lower mortality risk in the unadjusted analysis (hazard ratio [HR], 0.76; 95% CI, 0.70-0.82) but after adjusting for cofounders, PDE5i use was associated with elevated mortality risk relative to nitrate use alone (adjusted HR [aHR], 1.39; 95% CI, 1.28-1.51).

In the adjusted analyses, compared with nitrate use alone, PDE5i exposure was associated with an increased risk for:

• revascularization (aHR, 1.95; 95% CI, 1.78-2.13),
• MI (aHR, 1.72; 95% CI, 1.55-1.90),
• MACE (aHR, 1.70; 95% CI, 1.58-1.83),
• heart failure (aHR, 1.67; 95% CI, 1.48-1.90), 
• non-cardiovascular disease (CVD) death (aHR, 1.40; 95% CI, 1.27-1.54), and
• CVD death (aHR, 1.34; 95% CI, 1.11-1.62).

Stratified by type of nitrate, trends were similar for sublingual nitroglycerin and combination of nitrates as in the main analysis. For oral nitrates, however, no significant risk difference in mortality, CVD death, non-CVD death, MI, and revascularization was observed between oral nitrates alone or in combination with PDE5i.

This study was limited by its observational design. Additional study is needed for causal relationships to be made.

“[W]e show that in men with CVD that use nitrate medication, the concomitant use of PDE5i results in a significantly increased HR for both morbidity and mortality over time. […] The results are in line with current guidelines that suggest consideration before prescribing PDE5i to patients with CVD using nitrate medication.”

This article originally appeared on Neurology Advisor