NEJM 356:39-46 January 4, 2007 Number 1
Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson's Disease
Renzo Zanettini, M.D., Angelo Antonini, M.D., Gemma Gatto, M.D., Rosa Gentile, M.D., Silvana Tesei, M.D., and Gianni Pezzoli, M.D.
ABSTRACT
Background Ergot-derived dopamine receptor agonists, often used in the treatment of Parkinson's disease, have been associated with an increased risk of valvular heart disease.
Methods We performed an echocardiographic prevalence study in 155 patients taking dopamine agonists for Parkinson's disease (pergolide, 64 patients; cabergoline, 49; and non–ergot-derived dopamine agonists, 42) and 90 control subjects. Valve regurgitation was assessed according to American Society of Echocardiography recommendations. The mitral-valve tenting area was also measured and used as a quantitative index for leaflet stiffening and apical displacement of leaflet coaptation.
Results Clinically important regurgitation (moderate to severe, grade 3 to 4) in any valve was found with significantly greater frequency in patients taking pergolide (23.4%) or cabergoline (28.6%) but not in patients taking non–ergot-derived dopamine agonists (0%), as compared with control subjects (5.6%). The relative risk for moderate or severe valve regurgitation in the pergolide group was 6.3 for mitral regurgitation (P=0.008), 4.2 for aortic regurgitation (P=0.01), and 5.6 for tricuspid regurgitation (P=0.16); corresponding relative risks in the cabergoline group were 4.6 (P=0.09), 7.3 (P<0.001), and 5.5 (P=0.12). The mean mitral tenting area was significantly greater in ergot-treated patients and showed a linear relationship with the severity of mitral regurgitation. Patients treated with ergot derivatives who had grade 3 to 4 regurgitation of any valve had received a significantly higher mean cumulative dose of pergolide or cabergoline than had patients with lower grades.
Conclusions The frequency of clinically important valve regurgitation was significantly increased in patients taking pergolide or cabergoline, but not in patients taking non–ergot-derived dopamine agonists, as compared with control subjects. These findings should be considered in evaluating the risk–benefit ratio of treatment with ergot derivatives.
Source Information
From the Cardiac Rehabilitation Unit (R.Z., G.G., R.G.) and Parkinson Institute (A.A., S.T., G.P.), Istituti Clinici di Perfezionamento, Milan.
NEJM 356:29-38 January 4, 2007 Number 1
Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation
René Schade, M.D., Frank Andersohn, M.D., Samy Suissa, Ph.D., Wilhelm Haverkamp, M.D., Ph.D., and Edeltraut Garbe, M.D., Ph.D.
ABSTRACT
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.
Source Information
From the Department of Clinical Pharmacology, Charité Campus Mitte (R.S., F.A., E.G.), and the Department of Cardiology, Charité Campus Virchow (W.H.), Charité-Universitätsmedizin Berlin, Berlin; and the McGill Pharmacoepidemiology Research Unit, Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University Health Centre, Montreal (S.S.). |
