Dopamine agonists and the risk of cardiac-valve regurgitation

N Engl J Med. 2007 Jan 4;356(1):29-38. doi: 10.1056/NEJMoa062222.


Background: Case reports and echocardiographic studies suggest that the ergot-derived dopamine agonists pergolide and cabergoline, used in the treatment of Parkinson's disease and the restless legs syndrome, may increase the risk of cardiac-valve regurgitation.

Methods: We used data from the United Kingdom General Practice Research Database to identify a population-based cohort comprising 11,417 subjects 40 to 80 years of age who were prescribed antiparkinsonian drugs between 1988 and 2005. We conducted a nested case-control analysis within this cohort in which each patient with newly diagnosed cardiac-valve regurgitation was matched with up to 25 control subjects from the cohort, according to age, sex, and year of entry into the cohort. Incidence-rate ratios for cardiac-valve regurgitation with the use of different dopamine agonists were estimated by conditional logistic-regression analysis.

Results: Of 31 case patients with newly diagnosed cardiac-valve regurgitation, 6 were currently exposed to pergolide, 6 were currently exposed to cabergoline, and 19 had not been exposed to any dopamine agonist within the previous year. The rate of cardiac-valve regurgitation was increased with current use of pergolide (incidence-rate ratio, 7.1; 95% confidence interval [CI], 2.3 to 22.3) and cabergoline (incidence-rate ratio, 4.9; 95% CI, 1.5 to 15.6), but not with current use of other dopamine agonists.

Conclusions: In this study, use of the dopamine agonists pergolide and cabergoline was associated with an increased risk of newly diagnosed cardiac-valve regurgitation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / adverse effects
  • Cabergoline
  • Case-Control Studies
  • Cohort Studies
  • Dopamine Agonists / adverse effects*
  • Ergolines / adverse effects*
  • Female
  • Heart Valve Diseases / chemically induced*
  • Heart Valve Diseases / diagnosis
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Parkinson Disease / complications
  • Parkinson Disease / drug therapy
  • Pergolide / adverse effects*
  • Serotonin 5-HT2 Receptor Agonists*
  • Serotonin Receptor Agonists / adverse effects


  • Antiparkinson Agents
  • Dopamine Agonists
  • Ergolines
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin Receptor Agonists
  • Pergolide
  • Cabergoline