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Heart-Valve Disease Linked to Two Parkinson's Drugs
The ergot-derived dopamine agonists Permax (pergolide) and Dostinex (cabergoline) are associated with an increased risk of cardiac-valve regurgitation, two groups of European researchers reported.
The frequency of clinically important valvular heart disease was significantly increased in patients taking these drugs but not in those taking non-ergot-derived dopamine agonists, according to two independent reports in the Jan. 4 issue of the New England Journal of Medicine.
In the first study, René Schade, M.D., of Charité-Universitätsmedizin Berlin, and colleagues, used data from the United Kingdom General Practice Research Database to identify a population-based cohort of 11,417 patients, 40 to 80 years old, treated with anti-Parkinson's drugs from 1988 to 2005.
In a nested case-control analysis within this cohort, each patient with newly diagnosed cardiac-valve regurgitation was matched with up to 25 controls from the cohort, according to age, sex, and year of entry into the cohort. The mean age at study entry was 69, and the mean duration of follow-up was 4.2 years.
Using conditional logistic-regression analysis, the researchers found that the potent 5-hydroxy-tryptamine 2B (5-HT2B) agonists, Permax and Dostinex, were significantly associated with cardiac valve disease affecting the mitral, aortic, and tricuspid valves.
Of 31 case patients with newly diagnosed cardiac-valve regurgitation, six were currently taking Permax, six were taking Dostinex, and 19 had not been exposed to any dopamine agonist within the previous year.
The rate of cardiac-valve regurgitation increased with current use of Permax (incidence rate ratio, 7.1; 95% confidence interval [CI], 2.3 to 22.3). Dostinex also increased the incidence rate ratio (4.9; CI, 1.5 to 15.6).
However, the risk was not increased among patients treated with other ergot-derived dopamine agonists, bromocriptine or Dopergine (lisuride) or with dopamine agonists that are not derived from ergot, Requip (ropinirole) or Mirapex (pramipexole), the researchers found.
The current use of amantadine was the only other significant risk factor and was found in five patients. However, three patients also had current exposure to Dostinex, and one had been treated with Permax. The unexpected finding of an increased risk with amantadine requires further investigation, the researchers said, because this drug is not known to activate 5-HT2B receptors.
Preferential activation of this receptor has been shown to induce prolonged mitogenic effects in fibromyoblasts, which could induce valvular fibroplasia, the investigators said.
There are mechanistic grounds for believing that not all dopamine agonists are equally likely to be implicated in the development of a heart-valve disorder, Dr. Schade's team wrote. Some agents in this class, such as bromocriptine and Dopergine have antagonistic properties, and others, such as Requip and Mirapex have a low affinity for the 5-HT2B receptor.