title: Non-Ergot Dopamine Agonists Do Not Increase the Risk of Heart Failure in Parkinson's Disease Patients: A Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  In recent years, some observational studies suggested that pramipexole, a non-ergot dopamine agonist (DA) used for the treatment of Parkinson's disease (PD), may increase the risk of heart failure (HF). However, the limitations inherent in observational studies made it difficult to determine whether the excess of incident HF was related to the drug or to other determinants. Thus, some concerns remained regarding the increased putative HF risk associated with non-ergot DAs as a class or individually.
  
  
  METHODS
  In our meta-analysis, primary endpoint was the risk of incident HF in patients with PD treated with non-ergot DAs compared to those treated with monotherapy with levodopa. Secondary outcome measures were all-cause mortality and cardiovascular events. For these purposes, only randomized controlled trials (RCTs) were considered, provided that they offered complete outcome data pertaining to the incident HF, all-cause mortality and risk of cardiovascular events. Systematic searches were performed in the databases of PubMed, Embase and ClinicalTrial.gov up to May 2015. The effect size was estimated using the pooled relative risk (RR) of non-ergot DAs versus placebo on incident HF as well as on all-cause mortality or cardiovascular events.
  
  
  RESULTS
  Six out of 27 RCTs reported at least one case of incident HF; therefore, we included them in the RR estimate, whereas 13 RCTs were included in the meta-analysis for mortality rates and 22 RCTs were included to evaluate cardiovascular events. Treatment with non-ergot DAs did not reveal an increase in the risk of incident HF as compared with the placebo group (pooled RR: 0.95; 95% CI: 0.30 - 2.90; P = 0.893). Similarly, patients treated with non-ergot DAs did not show any significant differences compared to controls with regard to all-cause mortality (pooled RR: 0.617; 95% CI: 0.330 - 1.153; P = 0.13) as well as with regard to cardiovascular events (pooled RR: 1.067; 95% CI: 0.663 - 1.717; P = 0.789).
  
  
  CONCLUSIONS
  The use of non-ergot DAs in PD patients was not associated with an increased risk of incident HF, nor was it shown to increase the overall mortality or the risk of cardiovascular events compared to the PD patients taking monotherapy with levodopa alone. However, larger studies are warranted to confirm the cardiovascular safety of non-ergot DAs for PD management.
authors.affiliation: Cardiology Unit, Presidio Sanitario Intermedio "Elena d'Aosta", ASL Napoli 1 Centro, Napoli, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: De Vecchis
authors.affiliation: Cardiology Unit, Presidio Sanitario Intermedio "Elena d'Aosta", ASL Napoli 1 Centro, Napoli, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cantatrione
authors.affiliation: Cardiology Unit, Presidio Sanitario Intermedio "Elena d'Aosta", ASL Napoli 1 Centro, Napoli, Italy.
authors.forename: Damiana
authors.initials: D
authors.lastname: Mazzei
authors.affiliation: Heart Department, Interventional Cardiology, A.O.U. "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Baldi
authors.affiliation: Department of Cardiology, Second University of Napoli, Monaldi Hospital, Napoli, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Maio
keywords: Cardiovascular prevention; Heart failure; Non-ergot dopamine agonists; Parkinson’s disease