Background Ergot-derived dopamine receptor agonists, often usedin the treatment of Parkinson's disease, have been associatedwith an increased risk of valvular heart disease.
Methods We performed an echocardiographic prevalence study in155 patients taking dopamine agonists for Parkinson's disease(pergolide, 64 patients; cabergoline, 49; and non–ergot-deriveddopamine agonists, 42) and 90 control subjects. Valve regurgitationwas assessed according to American Society of Echocardiographyrecommendations. The mitral-valve tenting area was also measuredand used as a quantitative index for leaflet stiffening andapical displacement of leaflet coaptation.
Results Clinically important regurgitation (moderate to severe,grade 3 to 4) in any valve was found with significantly greaterfrequency in patients taking pergolide (23.4%) or cabergoline(28.6%) but not in patients taking non–ergot-derived dopamineagonists (0%), as compared with control subjects (5.6%). Therelative risk for moderate or severe valve regurgitation inthe pergolide group was 6.3 for mitral regurgitation (P=0.008),4.2 for aortic regurgitation (P=0.01), and 5.6 for tricuspidregurgitation (P=0.16); corresponding relative risks in thecabergoline 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 greaterin ergot-treated patients and showed a linear relationship withthe severity of mitral regurgitation. Patients treated withergot derivatives who had grade 3 to 4 regurgitation of anyvalve had received a significantly higher mean cumulative doseof pergolide or cabergoline than had patients with lower grades.
Conclusions The frequency of clinically important valve regurgitationwas significantly increased in patients taking pergolide orcabergoline, but not in patients taking non–ergot-deriveddopamine agonists, as compared with control subjects. Thesefindings should be considered in evaluating the risk–benefitratio 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.
Address reprint requests to Dr. Zanettini at the Cardiac Rehabilitation Unit, Via Bignami 1, Istituti Clinici di Perfezionamento, 20126 Milan, Italy, or at cardriab{at}icp.mi.it.
Dopamine Agonists and Valvular Heart Disease
Stephens J. W., Price D. E., Ionescu A., Linkova H., Ruzicka E., Penicka M., Kast R. E., Altschuler E. L., Ziegler J. L., Bukhman G. Y., Sartiani L., Cerbai E., Mugelli A., Schade R., Andersohn F., Garbe E., Zanettini R., Pezzoli G., Roth B. L.
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N Engl J Med 2007;
356:1676-1680, Apr 19, 2007.
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[Abstract][Full Text]
Lindsay, A.
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93: 645-647
[Full Text]
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