title: Cardiovascular and mortality risks in Parkinson's disease patients treated with entacapone.
abstract: 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.
authors: Office of Epidemiology and Surveillance, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993-0002, USA. david.graham1@fda.hhs.gov
authors: David J
authors: DJ
authors: Graham
authors: James R
authors: JR
authors: Williams
authors: Ya-Hui
authors: YH
authors: Hsueh
authors: Katlyn
authors: K
authors: Calia
authors: Mark
authors: M
authors: Levenson
authors: Simone P
authors: SP
authors: Pinheiro
authors: Thomas E
authors: TE
authors: Macurdy
authors: David
authors: D
authors: Shih
authors: Chris
authors: C
authors: Worrall
authors: Jeffrey A
authors: JA
authors: Kelman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002396:Catechols / Q000009:adverse effects / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000401:mortality*; D012306:Risk; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D002396:Catechols; D018491:Dopamine Agonists; D009570:Nitriles; D007980:Levodopa; C071192:entacapone