Parkinson's drugs again linked to heart valve seal failure

Two dopamine agonist treatments used to treat Parkinson's disease (PD), Eli Lilly's Permax (pergolide) and Pfizer's Dostinex (cabergoline), may raise the risk of heart valve leakage, according to two EU studies published in the New England Journal of Medicine.

The new findings support those observed in earlier studies.

The Charite-Universitatsmedizin Berlin study assessed dopamine agonist use among 31 patients prescribed a drug for PD and were later diagnosed with cardiac valve regurgitation, where the valve fails to seal properly in reverse-flow. Each case patient was matched up to 25 control subjects by age and sex. The case patients included six taking Permax, six on Dostinex and 19 who had not taken any dopamine agonist in the last year.

Results from the German study revealed that current use of Permax or Dostinex increased the risk of valve regurgitation by 7.1 and 4.9 times, respectively. Taking other dopamine agonists seemed to have no effect on the risk of cardiac valve regurgitation.

A parallel study at the Instituti Clinici di Perfezionamento Milan assessed valve regurgitation in 64 Permax users, 49 Dostinex users, 42 users of other dopamine agonists and 90 control subjects.

Regurgitation was observed in approximately 23 per cent of Permax users, 29 per cent of Dostinex users, while none of the users of other dopamine agonist products and control subjects exhibited valve problems. The severity of the regurgitation with Permax and Dostinex seemed to increase with higher dosages of the drugs.

Dr Bryan L Roth of the University of North Carolina also noted that in addition to stimulating dopamine receptors, both Permax and Dostinex stimulate serotonin receptors, a key step in the progression of drug-induced heart valve disease. He advises doctors to avoid prescribing potent serotonin receptor agonists, such as Permax and Dostinex.

About 73,000 prescriptions were written for Permax in 2005, representing USD 10.5 million in the billion-dollar market for Parkinson's drugs in the US , according to IMS Health. US sales of Dostinex totalled approximately USD 88 million in 2005, and about 87,000 prescriptions were written, according to Wolters Kluwer Health.