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

Ylva Trolle Lagerros; Alessandra Grotta; Sara Freyland; David Grannas; Daniel Peter Andersson

doi:10.1016/j.jacc.2023.10.041

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.

Authors

Ylva Trolle Lagerros¹, Alessandra Grotta², Sara Freyland³, David Grannas³, Daniel Peter Andersson⁴

Affiliations

¹ Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; Center for Obesity, Academic Specialist Center, Stockholm Health Services, Stockholm Sweden.
² Department of Public Health Sciences, Stockholm University, Stockholm, Sweden.
³ Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Medicine Huddinge H7, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: daniel.p.andersson@ki.se.

PMID: 38233015
DOI: 10.1016/j.jacc.2023.10.041

Abstract

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

Substances

Phosphodiesterase 5 Inhibitors
Nitrates
Cyclic Nucleotide Phosphodiesterases, Type 5