Two European studies add to mounting evidence linking two treatments for Parkinson's disease, pergolide and cabergoline, with valvular heart disease. The first was a case control study using routine data from UK general practices. The authors found a significantly increased risk of valve regurgitation in patients taking either drug for more than six months (incidence rate ratio 7.1; 95% CI 2.3 to 22.3 for pergolide and 4.9, 1.5 to 15.6 for cabergoline), particularly if they took more than 3 mg a day. In the second study, researchers measured valve regurgitation directly by echocardiography and found a higher incidence in patients taking these drugs than in matched controls without Parkinson's disease. Both studies reported drug related damage to all three heart valves.
Pergolide and cabergoline are dopamine agonists derived from ergot. Unlike other drug treatments for Parkinson's disease, they are also potent agonists at 5-hydroxytryptamine type 2B (5HT 2B) receptors, which are plentiful in heart valves. Other agonists at this receptor have already been implicated in valvular heart disease. Known agonists include appetite suppressants (fenfluramine, now banned from sale), drugs for treating migraine (dihydroergotamine, methysergide, and ergotamine), and the recreational drug ecstasy. A linked commentary (pp 6-9) urges drug manufacturers and regulatory agencies to screen compounds for their activity at the 5HT 2B receptor before starting clinical trials.
References
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