Phosphodiesterase-5 Inhibitor Use Is Associated with a 60-61% Relative Decrease in the Rate of Parkinson’s Disease: A Cohort Study Supporting the Need for a Phase Three Clinical Trial
Objective:
To evaluate the association between phosphodiesterase-5 inhibitor (PDE5i) use and Parkinson’s disease (PD) risk
Background:
Preclinical and clinical studies have supported the use of phosphodiesterase-5 inhibitors (PDE5i) to decrease the risk of Alzheimer’s disease (AD), including our recent report which demonstrated decreased odds of PDE5i use among patients with AD and related dementias (ADRD) compared to patients without ADRD among populations with erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary hypertension (pHTN)– three common chronic FDA-approved PDE5i indications. Our study demonstrated similar results using the more limited outcome of AD and the more inclusive outcome of ADRD, implying that PDE5i use may be associated with a decreased risk of other causes of dementia, including PD. To date, clinical investigations of PDE5i have evaluated its efficacy in reducing PD symptoms but not in preventing PD.
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 a decreased rate of PD among patients with ED and BPH over six years of follow-up. Available sample sizes for pHTN were insufficient to achieve required power.
Results:
We observed a 61% (95% CI: 33-77%) and 60% (95% CI: 36-75%) relative hazard reduction for PD associated with a history of PDE5i use among populations with ED (n[PDE5i+]=6080, n[PDE5i-]=3693) and BPH (n[PDE5i+]=3558, n[PDE5i-]=15534), respectively. Survival free from PD was higher for patients with than for patients without a history of PDE5i use among 70-80-year-old patients with ED and 50-60- and 70-80-year-old patients with BPH.
Conclusions:
History of PDE5i use is associated with a decreased rate of PD among patient populations with ED and BPH over a wide range of ages, supporting the need for a phase three clinical trial evaluating the use of PDE5i in the prevention of PD.