Affiliations: [a] Serviço de Medicina III, Hospital Pulido Valente, CHULN, Lisbon, Portugal
Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| [c] Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| [d] Serviço de Cardiologia, Hospital Universitário de Santa Maria, CAML, Centro Cardiovascular da Universidade de Lisboa – CCUL, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| [e] Serviço de Neurologia, Departamento de Neurociências e Saúde Mental, CHULN, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| [f] CNS – Campus Neurológico Sénior, Torres Vedras, Portugal
Correspondence to: Joaquim J. Ferreira, Laboratório de Farmacologia Clínica e Terapêutica,
Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal. Tel.: +351 21 7802120;
E-mail: [email protected].
Abstract: 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.