Risk of Death in Patients With Coronary Artery Disease Taking Nitrates and Phosphodiesterase-5 Inhibitors

J Am Coll Cardiol. 2024 Jan 23;83(3):417-426. doi: 10.1016/j.jacc.2023.10.041.


Background: Phosphodiesterase-5 inhibitor (PDE5i) treatment for erectile dysfunction is associated with lower mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI). There are conflicting results regarding the impact of PDE5i treatment on mortality in conjunction with nitrate medication.

Objectives: The purpose of this study was to investigate the association between PDE5i treatment and cardiovascular outcomes in men with stable coronary artery disease treated with nitrate medication.

Methods: Using the Swedish Patient Register and the Prescribed Drug Register we included men with previous MI or revascularization in 2006-2013 who had 2 dispensed nitrate prescriptions within 6 months. Exposure was defined as at least 2 filled prescriptions of any PDE5i. We performed multivariable Cox proportional hazard regression to estimate HRs with 95% CIs for all-cause, cardiovascular, and noncardiovascular mortality, MI, heart failure, cardiac revascularization, and major cardiovascular events (MACE).

Results: In total, 55,777 men were treated with nitrates and 5,710 men with nitrates and a PDE5i. The combined use of PDE5i treatment with nitrates was associated with higher mortality (HR: 1.39; 95% CI: 1.28-1.51), cardiovascular mortality (HR: 1.34; 95% CI: 1.11-1.62), noncardiovascular mortality (HR: 1.40; 95% CI: 1.27-1.54), MI (HR: 1.72; 95% CI: 1.55-1.90), heart failure (HR: 1.67; 95% CI: 1.48-1.90), cardiac revascularization (HR: 1.95; 95% CI: 1.78-2.13), and MACE (HR: 1.70; 95% CI: 1.58-1.83).

Conclusions: The use of a PDE5i in combination with nitrate medication in men with stable coronary artery disease may pose an increased hazard for cardiovascular morbidity and mortality. Careful patient-centered consideration before prescribing PDE5is to patients with cardiovascular disease using nitrate medication is warranted.

Keywords: cardiovascular diseases; erectile dysfunction; mortality; myocardial infarction; sildenafil; tadalafil.

MeSH terms

  • Coronary Artery Disease* / complications
  • Coronary Artery Disease* / drug therapy
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / therapeutic use
  • Erectile Dysfunction* / complications
  • Erectile Dysfunction* / drug therapy
  • Heart Failure* / drug therapy
  • Humans
  • Male
  • Myocardial Infarction* / complications
  • Myocardial Infarction* / drug therapy
  • Nitrates / therapeutic use
  • Phosphodiesterase 5 Inhibitors / therapeutic use


  • Phosphodiesterase 5 Inhibitors
  • Nitrates
  • Cyclic Nucleotide Phosphodiesterases, Type 5