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Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease

Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease. 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.;

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Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease

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  1. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease 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. Published in the New England Journal of Medicine January 4, 2007

  2. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Background • Ergot-derived dopamine receptor agonists, which are frequently used in the treatment of Parkinson’s disease, have been associated with an increased risk of valvular heart disease. • In particular, pergolide, cabergoline, and bromocriptine, all ergot-derived dopamine receptor agonists, have been related to the occurrence of valvular heart disease. Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  3. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Background • Although non-ergot-derived dopamine agonists may represent a valid alternative for the treatment of Parkinson’s disease, their safety with regard to fibrotic reactions has been questioned. • The goal of the present study was to assess the prevalence of valvular disease in patients treated with pergolide, cabergoline, or non-ergot-derived dopamine agonists and in a group of control subjects without Parkinson’s disease. Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  4. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Study Design 245 patients total: 155 patients attending the out-patient service of the Parkinson Institute of the Instituti Clinici di Perfezionamento, Milan between January and June 2005, and taking only one type of dopamine agonist for Parkinson’s disease for at least 12 months and 90 control subjects without Parkinson’s disease recruited from among relatives of patients, acquaintances of medical staff, or referred to echocardiography laboratory for arterial hypertension or fitness evaluation Convenience Sample. Pergolide Group n=64 Cabergoline Group n=49 Control Subjects n=90 Non-ergot-derived dopamine agonists n=42 transthoracic echocardiographic examination • Primary Endpoint: Valve regurgitation • Secondary Endpoint: Leaflet thickening, Mitral-valve tenting area Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  5. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Baseline Characteristics *Plus-minus values are means ± SD. The body-mass index is the weight in kg divided by the square of the height in m. NA denotes not applicable. Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  6. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Mitral Regurgitation Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  7. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Aortic Regurgitation N Engl J Med; 356(1): 39-46

  8. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Tricuspid Regurgitation N Engl J Med; 356(1): 39-46

  9. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Valvular Regurgitation Frequency (%) of moderate to severe (grade 3 to 4) valvular regurgitation in any valve • The frequency of clinically significant valve disease (grade 3 to 4 regurgitation) was significantly higher in the pergolide group (23.4%, p=0.001) and cabergoline group (28.6%, p<0.001) as compared to the control group (5.6%). • There was no significant difference in frequency of moderate to severe valvular regurgitation between the non-ergot-derived group (0%) and the control group (5.6%). p<0.001 p=0.001 Frequency of Valvular Regurgitation (%) p=0.17 n=49 n=90 n=64 n=42 Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  10. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Composite Regurgitation Score Mean composite regurgitation scores of all treatment groups • The mean composite regurgitation scores were significantly higher in both the pergolide group (p<0.001) and the cabergoline group (p<0.001) as compared with the control group. • There was no significant difference in mean composite regurgitation scores between the non-ergot-derived group and the control group. 5.14+1.84 p<0.001 4.8+2.01 p<0.001 3.27+2.02 3.4+1.29 p=0.44 Composite Regurgitation Score n=90 n=49 n=42 n=64 Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  11. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Leaflet Thickening Frequency (%) of leaflet thickening of any valve • Patients treated with ergot-derived dopamine agonists demonstrated a significantly higher frequency of localized or diffuse leaflet thickening. • No leaflet thickening was observed in the non-ergot-derived group or in the control group. p<0.001 p<0.001 Frequency of Leaflet Thickening (%) p=NA n=49 n=90 n=64 n=42 Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  12. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Mitral-Valve Tenting Mitral tenting area in each of the treatment groups • The mitral tenting area in each of the three drug treatment groups was significantly higher than that observed in the control group 3.1+0.80 p<0.001 2.95+0.81 p=0.001 2.8+0.62 p=0.002 2.37+0.49 Mitral-valve tenting area (cm2) n=90 n=49 n=42 n=64 Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  13. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Limitations • Limited non-randomized sample of patients used for analysis. • A larger, randomized comparison would be more definitive. Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  14. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Summary • 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. • The observed relationship between the severity of valvular functional impairment and the presence of the typical morphologic alterations found in patients in the ergot group supports the hypothesis of a fibrosing process involving the valve leaflets and subvalvular apparatus. Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

  15. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease: Summary • The finding of a significantly increased mean mitral tenting area in both patients treated with ergot-derived and those treated non-ergot-derived dopamine agonists, suggests that follow-up echocardiographic monitoring is advisable in all patients being treated with dopamine agonists for Parkinson’s disease. • In conclusion, the study demonstrates a significant increase in the risk of heart-valve regurgitation in patients being treated with ergot-derived dopamine-receptor agonists for Parkinson’s disease. Zanettini et al. N Engl J Med; 2007 Jan. 356(1): 39-46.

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