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.

Risk of myocardial infarction in Parkinson's disease: A systematic review and meta‐analysis

“…After title and abstract screening, 1953 articles were excluded. Finally, 20 studies with a total of 80,441 patients with PD and 802,857 controls were included in our qualitative and quantitative synthesis [16, 29–47]. The included studies comprised 12 cohorts, seven case–controls and one cross‐sectional study (Table 1).…”

“…After title and abstract screening, 1953 articles were excluded. Finally, 20 studies with a total of 80,441 patients with PD and 802,857 controls were included in our qualitative and quantitative synthesis [16,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47].…”

Exercise-mitigated sex-based differences in aging: from genetic alterations to heart performance

“…Moreover, low activity of the Comt gene is associated with a decreased risk of myocardial infarction in human subjects (32). It is noteworthy that Graham et al (33) discussed that MAO-B inhibitors and COMT inhibitors do not increase mortality compared to placebo; however, the link between the COMT inhibitors and acute myocardial infarction remains to be proven.…”

Treatment of advanced Parkinson's disease

“…dyskinesia induction), but also very helpful in instilling a sense of caution when using COMT inhibitors (29). Additionally in the STRIDE-PD study there was an increase in acute myocardial infarction (29), though in more recent studies it was not associated with entacapone (entacapone-treated PD patients) (31). …”