Dopamine agonists and valvular heart disease in patients with Parkinson's disease: evidence and mystery

High doses of the ergot dopamine agonists, pergolide and cabergoline, frequently cause valvular regurgitation and, somewhat less frequently, valvular heart disease (VHD) in Parkinson's disease. Most patients with valvular regurgitation have no cardiac signs and symptoms. Reports from Asian countries showed no significant increase of valvular regurgitation associated with low-dose pergolide, but a high dose of cabergoline was associated with a high frequency of valvular regurgitation. This may be due to differences in the optimal recommended doses of these drugs between Asian and western countries. In Asian countries, the recommended daily dose of pergolide is low compared with that in western countries, whereas the dose of cabergoline used in Asian countries is the same as that in western countries. Stimulation of serotonin 5HT2B receptors has been considered as pathogenic mechanism underlying ergot dopamine agonist – induced fibrotic VHD. Ropinirole, a non-ergot dopamine agonist that has low affinity to 5HT2B receptors, rarely causes fibrosis of systemic organs and cardiac valvulopathy. Pramipexole,which has no affinity to 5HT2B receptors, may cause fibrosis of systemic organs. These observations remind us that postmarketing surveillance of drug side effects is very important to monitor the safety of these widely used agents.