Cardiovascular Adverse Events Reported in Placebo Arm of Randomized Controlled Trials in Parkinson’s Disease

BACKGROUND: Parkinson's disease and cardiovascular disease are highly prevalent conditions in the elderly. Evidence shows inconsistent findings regarding the association between Parkinson's disease and cardiovascular events. OBJECTIVE: We sought to evaluate the proportion of cardiovascular adverse events among Parkinson's disease patients included in the placebo arm of randomized controlled trials. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2017. Randomized, placebo-controlled trials in Parkinson's disease were included. The primary outcome was the proportion of major cardiovascular adverse events, defined as myocardial infarction, stroke, peripheral artery disease, and sudden death. A random-effects meta-analysis was performed to derive pooled estimates of the proportion of adverse events and corresponding 95% confidence intervals (CIs). RESULTS: 236 randomized controlled trials were included, 80% (n = 189; 14704 patients) of which reported data on cardiovascular adverse events. The pooled proportion of major cardiovascular events ranged from 0.00% to 0.06% and the proportion of all cardiovascular adverse events was 3.33% (95% CI: 2.14, 4.70%), and ranged from 1.71% in de novo Parkinson's disease patients to 4.56% in patients receiving levodopa as their only antiparkinsonian medication. The most common adverse events were hypertension and orthostatic hypotension. CONCLUSIONS: These results suggest that the proportion of major cardiovascular adverse events is low and that blood pressure abnormalities are the most frequent cardiovascular adverse event.