Phosphodiesterase-5 Inhibitor Use Is Associated with a 56-71% Relative Decrease in the Rate of Ischemic Stroke: A Cohort Study Supporting the Need for a Phase Three Clinical Trial
Objective:
To evaluate the association between phosphodiesterase-5 inhibitor (PDE5i) use and ischemic stroke risk
Background:
We recently reported decreased odds of PDE5i use among patients with Alzheimer’s disease and related dementias (ADRD) in populations with erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary hypertension (pHTN)– three common PDE5i indications. Our study implies that PDE5i use may be associated with a decreased risk of various causes of dementia, including ischemic stroke. Preclinical studies evaluating PDE5i and ischemic stroke damage demonstrate inconsistent conclusions. To date, clinical studies evaluating PDE5i and ischemic stroke risk have been performed only in patients following implantation of left ventricular assist devices.
Design/Methods:
We conducted a retrospective cohort study using the electronic medical record database from a large healthcare system to evaluate whether PDE5i use is associated with decreased rates of ischemic stroke among patients with ED, BPH, and/or pHTN over six years of follow-up.
Results:
We observed a 56-71% relative hazard reduction for ischemic stroke associated with a history of PDE5i use among populations with ED (n[PDE5i+]=5989, n[PDE5i-]=3696), BPH (n[PDE5i+]=3520, n[PDE5i-] =15308), and pHTN (n[PDE5i+]=393, n[PDE5i-]=3314). Survival free from ischemic stroke was higher for patients with than for patients without a history of PDE5i use among 50-60-, 60-70-, and 70-80-year-old patients with ED and BPH. As pHTN is the only chronic PDE5i indication for women, we stratified patients with pHTN by sex and observed higher survival free from stroke among patients with than among patients without a history of PDE5i use for both sexes.
Conclusions:
History of PDE5i use is associated with decreased rates of ischemic stroke among patient populations with ED, BPH, and pHTN, among a wide range of ages, and among both men and women. Our research supports the need for a phase three clinical trial to evaluate the use of PDE5i in the prevention of ischemic stroke.