title: Cabergoline use and risk of fibrosis and insufficiency of cardiac valves. Meta-analysis of observational studies.
abstract: BACKGROUND
  Therapy with ergot-derivative dopamine agonists (ergot-DAs) is suspected to cause or promote the development of insufficiency and regurgitation in previously normal cardiac valves. Thus, we conducted a systematic review and meta-analysis of the literature to determine whether administration of cabergoline, i.e., an ergot-DA used to treat Parkinson's disease (PD) or hyperprolactinemia, is associated with an increased risk of valve regurgitation compared with pharmacological regimens not comprising ergot-DAs or with no therapy.
  
  
  METHODS
  Observational studies were selected from the Pubmed and Embase databases. Studies had to have assessed the prevalence, odds, or risk of cardiac valve regurgitation in patients who underwent chronic treatment with cabergoline for PD or hyperprolactinemia compared with patients with the same diseases whose therapy did not include cabergoline or another ergot-DA. Separate meta-analyses were performed for PD and hyperprolactinemia patients.
  
  
  RESULTS
  On the basis of five studies, 634 PD patients were taking cabergoline, while 9,120 PD patients were treated with dopa/dopamine decarboxylase inhibitor, alone or associated with a non-ergot DA. Valvular regurgitation of any degree - at one cardiac valve or more - was more frequent in PD patients who were taking cabergoline compared to those treated with a non-ergot DA agent or not treated with any dopamine agonist [adjusted (inverse variance: iv) odds ratio: 7.25 95 % CI: 3.71-14.18; p < 0.0001]. On the other hand, pooled data from seven studies showed that patients with hyperprolactinemia who were taking cabergoline (n = 444) exhibited significantly higher odds of mild- to-moderate tricuspid regurgitation compared to untreated controls (n = 954) [adjusted (iv) odds ratio: 1.92 95 % CI:1.34-2.73; p = 0.0003]. No significant differences in mitral or aortic valve regurgitation were detected between hyperprolactinemic patients taking cabergoline and controls.
  
  
  CONCLUSIONS
  In PD patients, the risk of valvular regurgitation of any grade involving one or more cardiac valves was proven to be strongly associated with cabergoline treatment. Furthermore, based on our results, hyperprolactinemic patients taking cabergoline have an increased risk of mild-to-moderate tricuspid valve regurgitation.
authors.affiliation: Cardiology Unit , Presidio Sanitario Intermedio"Elena d'Aosta", Via Cagnazzi 29, 80137, Naples, Italy, r.de.vecchis@alice.it.
authors.forename: R
authors.initials: R
authors.lastname: De Vecchis
authors.forename: C
authors.initials: C
authors.lastname: Esposito
authors.forename: C
authors.initials: C
authors.lastname: Ariano
mesh_terms: D000077465:Cabergoline; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use; D004873:Ergolines / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis; D006349:Heart Valve Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D009206:Myocardium / Q000473:pathology*; D064887:Observational Studies as Topic; D015995:Prevalence; D012307:Risk Factors
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D000077465:Cabergoline