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. OBJECTIVES: 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. CONCLUSION: 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.