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

Article type: Research Article

Authors: Alves, Mariana^{a; b; c} | Caldeira, Daniel^{b; c; d} | Rato, Miguel Leal^{b; c; e} | Duarte, Gonçalo S.^{b; c} | Ferreira, Afonso N.^{b; c; d} | Ferro, José^{c; e} | Ferreira, Joaquim J.^{b; c; f; *}

Affiliations: [a] Serviço de Medicina III, Hospital Pulido Valente, CHULN, Lisbon, Portugal | [b] 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: [*] 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: jferreira@medicina.ulisboa.pt.

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.

Keywords: Parkinson’s disease, randomized controlled trials, stroke, myocardial infarction, hypertension, orthostatic hypotension, cardiovascular diseases

DOI: 10.3233/JPD-191907

Journal: Journal of Parkinson's Disease, vol. 10, no. 2, pp. 641-651, 2020