Parkinson's Drugs: Heart Damage Link?

Researchers Raise Concerns About Damage to Heart Valves From 2 Parkinson's Drugs

From the WebMD Archives

Jan. 3, 2007 -- Two drugs used in the treatment of Parkinson's disease appear to increase the risk of heart valve disease, according to new research that also raises safety questions about similar-acting drugs.

The drugs pergolide, marketed as Permax, and cabergoline, sold as Dostinex, were associated with heart valve damage in two European studies published in the Jan. 4 issue of the New England Journal of Medicine.

Both drugs are in a class known as ergot-derived dopamine receptor agonists, and both have been linked to heart valve issues in earlier case reports.

"We showed that treatment with either pergolide or cabergoline for more than six months was strongly associated with an increase in valve-related heart disease," Edeltraut Garbe, MD, PhD, tells WebMD. "No increase in risk was seen in patients treated with other dopamine agonists."

Heart Valves and Parkinson's Drugs

Garbe and colleagues from a German research center compared treatment histories among Parkinson's disease patients who did and did not develop heart valve disease.

Heart valves are one-way valves that keep blood flowing in the right direction through your heart. If people have problems with their heart valves then blood may not move the way it should.

The study involved more than 11,000 patients prescribed anti-Parkinson drugs from the U.K. registered in a nationwide database.

The rate of heart valve disease was seven times higher than the rate in a matched comparison group of patients from the group who didn't develop heart valve disease among current pergolide-treated patients -- and five times higher among patients being treated with cabergoline. No increase was seen among current users of other types of dopamine-directed drugs.

Checking for Heart Valve Disease

In a separate study from Italy, researchers performed echocardiograms on Parkinson's patients being treated with either ergot-derived or nonergot-derived dopamine-targeting drugs. An echocardiogram is an ultrasound of the heart which can provide information on the heart's chambers and valves and how well blood is pumping through the heart.

Compared with an age-matched group without Parkinson's disease, patients taking pergolide or cabergoline had significantly more evidence of heart valve disease.

Continued

Clinically important evidence of valve damage was seen in roughly 5% of the comparison group, compared with 23% of patients taking pergolide and 28% of patients taking cabergoline.

Garbe says it is clear from the two studies that patients taking either pergolide or cabergoline should be monitored closely for heart valve damage.

"We aren't saying that these drugs should not be used," she says. "I think if patients are appropriately followed they can be prescribed. But neurologists and other treating physicians have to be made aware of the risks."

A spokesman for pergolide manufacturer Valeant Pharmaceuticals International tells WebMD that the company would have no direct comment on the two new studies. But a company statement reaffirmed the safety of the drug.

"Permax (pergolide) is a safe and effective treatment for patients with Parkinson's disease," the statement reads. "Although Valeant no longer promotes the product, we still make it available for those who prescribe it. We also routinely communicate with the FDA and recently worked with the agency to modify the label to advise physicians that the product, like other dopamine agonists, should be used with caution."

Important Mechanism

Bryan Roth, MD, PhD, tells WebMD that the two Parkinson's drugs appear to cause heart damage in the same way that the now notorious weight lossmedication fen-phen did.

Fen-phen was voluntarily withdrawn from the market a decade ago, following reports of life-threatening heart valve disease. Another related diet drug marketed by Wyeth-Ayerst Laboratories as Redux was also withdrawn.

The diet drugs and their byproducts have been shown by Roth and others to selectively bind to specific receptors in human heart valve cells, known as 5-HT2B. The same mechanism was seen in the two implicated Parkinson's drugs.

"The two new studies provide the best evidence yet for validating this particular mechanism," Roth tells WebMD. "5-HT2B receptor activity predicts heart valve disease."

Roth, who is a professor of pharmacology at the University of North Carolina School of Medicine, Chapel Hill, says all investigational drugs and byproducts should be screened for 5-HT2B activity in the future.

In an editorial published along with the two studies, Roth called on doctors to avoid prescribing the drugs.

WebMD Health News Reviewed by Louise Chang, MD on January 03, 2007

Sources

SOURCES: Schade, R. and Zanettini, R. The New England Journal of Medicine, Jan. 4, 2007; vol 356: pp 29-46. Edeltraut Garbe, MD, PhD, Charite Camps Mitte, Charite-Universitatsmedizin, Berlin. Bryan Roth, MD, PhD, director, National Institute of Mental Health Psychoactive Drug Screening Program; professor of pharmacology and medicinal chemistry, University of North Carolina at Chapel Hill.

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