title: Risks of Cardiac Valve Regurgitation and Heart Failure Associated with Ergot- and Non-Ergot-Derived Dopamine Agonist Use in Patients with Parkinson's Disease: A Systematic Review of Observational Studies.
abstract: BACKGROUND
  Dopamine agonists (DAs) are commonly used in the therapy of Parkinson's disease (PD). However, several observational studies have suggested a putative association between DAs and specific cardiac adverse events.
  
  
  OBJECTIVE
  The aim of this study was to systematically review and summarize the available epidemiologic evidence on the association between use of ergot- and non-ergot-derived DAs and the risk of valvular heart disease, specifically cardiac valve regurgitation (CVR) and heart failure (HF) in patients with PD.
  
  
  METHODS
  The databases MEDLINE/PubMed and EMBASE were searched for all relevant articles published before February 2015. Studies were eligible if they met the following inclusion criteria: exposure to any approved non-ergot- or ergot-derived DA, presentation of original data, inclusion of an unexposed reference group, and valvular heart disease or heart failure as the primary outcome of interest.
  
  
  RESULTS
  Thirteen publications for CVR were identified (two nested case-control, one cohort and ten cross-sectional studies). Compared with non-ergot DAs or other anti-parkinsonian drugs, exposure to ergot-derived DAs pergolide and cabergoline was associated with an increased risk of CVR among PD patients. Incidence rate ratios (IRR) in the nested case-control and cohort studies ranged from 2.00 to 7.10 and 4.58 to 4.90, respectively. Longer treatment duration and higher dose of those DAs was also associated with a higher risk of CVR. Risk of HF was estimated in three nested case-control studies and one cohort study. Use of cabergoline (IRR range 1.30-2.39) and the non-ergot-derived DA pramipexole (IRR range 1.40-1.81) was associated with a higher HF risk among patients with PD. Pergolide may also be associated with a higher risk of HF.
  
  
  CONCLUSIONS
  Despite the heterogeneous methodological approaches of the included studies, there is strong evidence that treatment with pergolide and cabergoline is associated with a higher risk of CVR, and moderate evidence that treatment with pramipexole and cabergoline is associated with a higher risk of HF in patients with Parkinson's disease.
authors.affiliation: Department of Epidemiology and Biostatistics, and of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Tanja
authors.initials: T
authors.lastname: Tran
authors.affiliation: Department of Epidemiology and Biostatistics, and of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: James M
authors.initials: JM
authors.lastname: Brophy
authors.affiliation: Department of Epidemiology and Biostatistics, and of Medicine, McGill University, Montreal, Quebec, Canada.|Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, McGill University, 3755 Cote Ste-Catherine, Montreal, Quebec, H3T 1E2, Canada.
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
authors.affiliation: Department of Epidemiology and Biostatistics, and of Medicine, McGill University, Montreal, Quebec, Canada. christel.renoux@mcgill.ca.|Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, McGill University, 3755 Cote Ste-Catherine, Montreal, Quebec, H3T 1E2, Canada. christel.renoux@mcgill.ca.|Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. christel.renoux@mcgill.ca.
authors.forename: Christel
authors.initials: C
authors.lastname: Renoux
mesh_terms: D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D004876:Ergot Alkaloids / Q000009:adverse effects / Q000627:therapeutic use; D006333:Heart Failure / Q000139:chemically induced / Q000453:epidemiology*; D006349:Heart Valve Diseases / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D064887:Observational Studies as Topic; D010300:Parkinson Disease / Q000188:drug therapy* / Q000453:epidemiology; D012306:Risk
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D004876:Ergot Alkaloids