Cardiovascular and mortality risks in Parkinson's disease patients treated with entacapone


  • Current address for Dr. Williams: Biogen Idec, Cambridge, MA, USA.

  • Funding agencies: This study was funded by the Centers for Medicare & Medicaid Services (CMS) and the Food and Drug Administration (FDA) under an intra-agency agreement. The views expressed are the authors and not necessarily those of the CMS, the FDA, or the Department of Health and Human Services.

  • Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article.

Correspondence to: Dr. David J. Graham, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Building 22, Room 4314, Silver Spring, MD 20993-0002;


The controlled trial Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) reported an unexpected increase in acute myocardial infarction (AMI) with entacapone use in patients with Parkinson's disease (PD). The authors investigated whether entacapone increased cardiovascular and mortality risk compared with the use of a non-levodopa dopamine agonist (DA) or a selective monoamine oxidase type-B inhibitor (MAOBI). Using national Medicare data, a new-user cohort of elderly patients with PD treated with entacapone was propensity score (PS) matched with new users of either DA or MAOBI. The PS model included variables for sociodemographics, cardiovascular disease, medications, prior PD treatment, and comorbidities. Cox proportional hazards regression was used to compare on-therapy time to event for AMI, stroke, and death with DA-MAOBI as a reference. Study cohorts included 8681 entacapone-treated and 17,362 DA-MAOBI-treated initators who were followed for 2569 and 5385 person-years, respectively. Cohorts were closely balanced for all covariates. During follow-up, there were 106 AMIs, 89 strokes, and 201 deaths. The hazard ratio (HR) and 95% confidence interval (CI) associated with entacapone use was 0.86 (95% CI, 0.57–1.30) for AMI, 0.85 (95% CI, 0.54–1.35) for stroke, and 0.79 (95% CI, 0.58–1.07) for death. The risk was unchanged for treatment of≤6 months’ and>6 months’ duration and was unaffected by adjustment for time-varying levodopa use during follow-up. The risk of each endpoint was not differentially affected by diabetes, ischemic heart disease, or kidney failure status. However, the risk of stroke was modified by the presence (HR, 2.09; 95% CI, 0.98–4.45) or absence (HR, 0.51; 95% CI, 0.27–0.95) of advanced PD-related morbidities (P value for interaction=0.004). Entacapone was not associated with an increased risk of AMI, stroke, or death in elderly patients with PD. © 2013 Movement Disorder Society