Risk of cardiac valve fibrosis and other fibroses with dopamine agonist use in Parkinson's disease

Objective: To explore the association between dopamine agonists (DAs) and cardiac valve regurgitation (CVR) or pleural/pulmonary/pericardial/retroperitoneal fibroses in patients with Parkinson’s disease (PD). Background: There is increasing evidence on ergot DA-induced cardiac valve fibrosis (i.e. regurgitation) in PD patients while the association between DA use and other fibroses is still unclear. Methods: A nested case control study was conducted in a cohort of PD patients who were newly treated with DAs or Levodopa. Study patients were identified from over 6 million persons in THIN (UK), Health Search-Thales (Italy), and IPCI (NL) general practice databases. Cases of CVR and fibroses were validated by manual review of medical records and specialist letters. Controls were matched to cases on age, gender, index date and database. Relative risks and 95% confidence intervals (CI) of CVR and fibroses were calculated for different DAs, compared to levodopa. Results: In the study cohort of 19,656 PD patients (7,890 DA users, 11,766 levodopa users), 85 incident cases of CVR were identified during follow-up. Compared to levodopa, only cabergoline was associated with significantly increased risk of CVR (OR:4.6; 95%CI:2.4-8.8). The risk was statistically significant after 6 months of therapy (OR:7.4; 95%CI:3.7-15.0) and was highest in those patients switching from pergolide (OR:60.7; 95%CI:12-308) and after the first specific safety warning in 2004 (OR:5.1; 95%CI:2.5-10.5). There was no association between any DA and other fibroses (N.cases513). Conclusions: Increased risk of CVR was observed only in PD patients using cabergoline for more than 6 months. Detection bias and previous exposure to pergolide may partly account for this risk. No increase in the risk of other fibroses for any DA was found.