Level 2: Mid-level evidence

Some dopamine agonists (pergolide [Permax] or cabergoline [Dostinex]) used to treat Parkinson’s disease may be associated with cardiac-valve regurgitation, based on a case-control study (N Engl J Med. 2007;356:29-38) and a cohort study (N Engl J Med. 2007;356:39-46). The nested case-control study was conducted within a cohort of 11,417 patients aged 40-80 years in the United Kingdom General Practice Research Database who were prescribed antiparkinsonian drugs (levodopa [Sinemet], selegiline [Eldepryl, Emsam, Zelapar], bromocriptine [Parlodel], cabergoline, pergolide, lisuride [Dopergine], pramipexole [Mirapex], or ropinirole [Requip]) between the years 1988 and 2005. Thirty-one patients had newly diagnosed mitral regurgitation (26 cases), aortic regurgitation (12 cases), or tricuspid regurgitation (three cases); eight cases involved multiple valves. Compared with 663 controls matched for age, sex, and year of entry, pergolide and cabergoline were associated with cardiac-valve regurgitation. The incidence rate ratio was 7.1 with pergolide, based on six cases (19% cases vs. 4% controls), while the incidence rate ratio was 4.9 with cabergoline, based on six cases (19% cases vs. 5% controls). No case patients had exposure to bromocriptine, lisuride, pramipexole, or ropinirole, and few controls (0-3%) had exposure to these drugs.

The cohort study included patients with Parkinson’s disease who had echocardiography: 64 patients taking pergolide for at least 12 months, 49 patients taking cabergoline for at least 12 months, 42 patients taking a non-ergot-derived dopamine agonist (pramipexole or ropinirole) for at least 12 months, and 90 controls recruited from relatives of patients or acquaintances of medical staff. Pergolide was associated with moderate-to-severe mitral regurgitation in nine patients (14%), moderate-to-severe aortic regurgitation in nine patients (14%), and moderate-to-severe triscupid regurgitation in four patients (6%). Cabergoline was associated with moderate-to-severe mitral regurgitation in five patients (10%), moderate-to-severe aortic regurgitation in 12 patients (24%), and moderate-to-severe tricuspid regurgitation in three patients (6%). Two control patients (2%) had moderate-to-severe mitral regurgitation, three (3%) had moderate-to-severe aortic regurgitation, and one (1%) had moderate-to-severe tricuspid regurgitation. The rate of any moderate-to-severe cardiac-valve regurgitation was zero for patients exposed to non-ergot-derived dopamine agonists, 6% for controls, 23% for pergolide (NNH 5), and 29% for cabergoline (NNH 4).

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