(203) Phosphodiesterase-5 Inhibitor Use and Progression to Heart Failure in Men with Coronary Artery Disease and Erectile Dysfunction
Authors: Ha A , Wayne G , Jacobs M , Kalogeropoulos A , Alukal J 
Published: May 2023

Abstract

Introduction
Erectile dysfunction (ED) is defined as an inability to reach or sustain an erection for satisfactory intercourse, and this condition affects more than 10 million men in the United States alone. Coronary artery disease (CAD) and ED often co-occur due to shared vascular risk factors for this condition. Phosphodiesterase-5-inhibitors (PDE5i) such as sildenafil and tadalafil are approved as first line treatments for ED, when early trials have demonstrated marked improvements in erectile function. PDE5i such as tadalafil have also been associated with decreased risk of death and cardiovascular disease, as it may alter endothelial function to improve myocardial perfusion and cardiac contractility. To date, information specific to the type of PDE5i used in relation to their perceived cardiac benefits has been limited.

Objective
We investigated whether the choice of PDE5i may impact progression to heart failure and other major adverse cardiac events (MACE) among men with both CAD and ED. We hypothesized that tadalafil, with its high affinity to PDE5 receptors compared with sildenafil, may provide greater clinical benefits in reducing MACE.

Methods
A retrospective, propensity-matched, cohort study was performed using the TriNetX Research Network. Patients with an ICD-10 diagnosis of CAD and ED but without pulmonary hypertension were captured from January 2011 to December 2016, with follow up restricted to 5 years. Patients were subdivided and analyzed via pairwise fashion according to known prescriptions for tadalafil, sildenafil, or no treatment (NT). Propensity matching was performed using baseline comorbidities of hypertension, ischemic heart disease, cerebral infarction, diabetes, and hyperlipidemia. Outcomes of interest included 5-year rates of heart failure (HF), acute myocardial infarction (MI), and mortality.

Results
Prior to propensity score matching, significant differences in baseline comorbidities were noted, with the highest rates of hypertension (9,653 [79.0%]), ischemic heart disease (9,109 [74.6%]), hyperlipidemia (8,541 [69.9%]), and cerebral infarction (690 [5.6%]) in the sildenafil group, and diabetes in the NT group (8,521 [38.2%]). Following propensity score matching, no significant differences were noted (Table 1). When compared with NT, both tadalafil and sildenafil were associated with reduced progression to HF, MI, and overall mortality. Most importantly, compared with sildenafil, tadalafil demonstrated lower progression to HF (HR: 0.85 [0.77-0.94]), MI (HR: 0.86 [0.76-0.97]) and mortality (HR: 0.85 [0.76-0.95]) (Table 2, Figure 1).

Conclusions
Tadalafil use was associated with a significant reduction in progression to HF, MI, and mortality, compared with sildenafil or no treatment. These preliminary results may signal meaningful clinical differences in drug choice for men suffering from CAD and ED, and therefore require further inquiry.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Endo.