Parkinson's drugs can cause heart damage-studies


By Gene Emery and Toni Clarke

BOSTON, Jan 3 (Reuters) - Two Parkinson's disease drugs cause the same kind of heart damage that led to the withdrawal of the diet drug combination "fen-phen," according to two studies published on Wednesday.

Patients taking the drugs pergolide, developed by Eli Lilly & Co. <LLY.N> and sold under the brand name Permax, and cabergoline, developed by Pfizer Inc. <PFE.N> and sold under the brand Dostinex, had a sharply higher risk of heart valve damage than those taking other therapies, the studies said.

The studies, one of which analyzed the records of 11,417 patients in Britain and one of which tested 245 patients in Italy, reinforce the results of earlier, smaller studies showing that drugs which activate a cellular receptor known as 5-HT2b can cause damage to the heart valve, a serious condition that can lead to heart failure and sudden death.

"We recommend that physicians not prescribe drugs that have this biochemical property," said Bryan Roth, a researcher at the University of North Carolina, Chapel Hill, who was not involved in the trials but viewed the data and commented on it in The New England Journal of Medicine, where both studies appeared.

Such drugs also include the migraine headache drug ergotamine and the amphetamine derivative known as "ecstasy."

Roth said his team, in a separate piece of research that has yet to be published or reviewed by the scientific community, has identified several other big-selling drugs that have until now not been known to activate the 5-HT2b receptor.

He declined to reveal the names of the drugs until the research has been published.

"We recommend that every drug be screened at this receptor before it goes into humans," Roth told Reuters in an interview. "It costs just pennies per drug for such a screen."

The British study showed that patients taking pergolide were 7.1 times more likely to develop heart valve damage than those who took other treatments. Patients taking the highest doses of the drug had a 37 times greater risk.

The study showed that patients taking cabergoline were 4.9 times more likely to develop heart valve damage. At higher doses patients were 50.3 times more likely to suffer damage.

Both drugs are available in generic form.

A second study, conducted in Italy, tested 245 people, of whom 155 had Parkinson's disease. Of the diseased population, one group received pergolide, one group received cabergoline, and one group received an alternative Parkinson's treatment. The non-diseased control group received nothing.

The results showed that 23.4 percent of patients taking pergolide and 28.6 percent of patients taking cabergoline suffered heart damage, compared to just 5.6 percent in the control group.

"These are huge risks," said Roth. He said they were similar to the kind of damage seen with fen-phen, whose main ingredients were withdrawn in 1997 and forced the drug-maker Wyeth <WYE.N> to take more than $21 billion in charges to cover liabilities.

Wyeth's recalled drugs were fenfluramine, or Pondimin, and dexfenfluramine, or Redux. To make fen-phen, one or the other was combined with another drug called phentermine that is still sold by other companies.

Wyeth, then called American Home Products, recalled Pondimin and Redux after some of the 6 million Americans who had taken fen-phen developed heart-valve problems.

Roth said pergolide is also used to treat restless leg syndrome, a condition in which patients feel a crawling sensation in their legs combined with a need to move them.

Thanks for the info, ZF.

From the study:
NEJM: Volume 356:29-38 January 4, 2007 Number 1


Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation
René Schade, M.D., Frank Andersohn, M.D.,

"In conclusion, our study showed that treatment with either pergolide or cabergoline, particularly at daily doses greater than 3 mg and for periods of 6 months or longer, was associated with a substantially increased risk of newly diagnosed cardiac-valve regurgitation. There was no evidence of such an increase in risk with the use of other dopamine agonists."

ABSTRACT

Background Case reports and echocardiographic studies suggest that the ergot-derived dopamine agonists pergolide and cabergoline, used in the treatment of Parkinson's disease and the restless legs syndrome, may increase the risk of cardiac-valve regurgitation.

Methods We used data from the United Kingdom General Practice Research Database to identify a population-based cohort comprising 11,417 subjects 40 to 80 years of age who were prescribed antiparkinsonian drugs between 1988 and 2005.

We conducted a nested case–control analysis within this cohort in which each patient with newly diagnosed cardiac-valve regurgitation was matched with up to 25 control subjects from the cohort, according to age, sex, and year of entry into the cohort. Incidence-rate ratios for cardiac-valve regurgitation with the use of different dopamine agonists were estimated by conditional logistic-regression analysis.

Results Of 31 case patients with newly diagnosed cardiac-valve regurgitation, 6 were currently exposed to pergolide, 6 were currently exposed to cabergoline, and 19 had not been exposed to any dopamine agonist within the previous year. The rate of cardiac-valve regurgitation was increased with current use of pergolide (incidence-rate ratio, 7.1; 95% confidence interval [CI], 2.3 to 22.3) and cabergoline (incidence-rate ratio, 4.9; 95% CI, 1.5 to 15.6), but not with current use of other dopamine agonists.

Conclusions In this study, use of the dopamine agonists pergolide and cabergoline was associated with an increased risk of newly diagnosed cardiac-valve regurgitation.

"Roth said his team, in a separate piece of research that has yet to be published or reviewed by the scientific community, has identified several other big-selling drugs that have until now not been known to activate the 5-HT2b receptor.

He declined to reveal the names of the drugs until the research has been published."

Now that's a real case of lack of transparency. "Aw come on give us a hint, please tell us which medicines are killing people. Pretty please."

paula

Paula, they may be other ergot derived drugs. I used to take ergotamine for migraines that I used to get. Thank god those days are over. It may be other migraine medicines too:

5-Hydroxytryptamine (5-HT) and the initiation of migraine: new perspectives

1994

Abstract

The hypothesis that 5-hydroxytryptamine (5-HT) acting through 5-HT2c receptors is a key factor in the initiation of migraine has been re-evaluated in the light of recent basic and clinical scientific developments. The key findings are that nitric oxide is an important trigger for migraine, that 5-HT2B/5-HT2C receptors are present on endothelial cells and trigger nitric oxide release when activated and that supersensitivity of the 5-HT2B/5-HT2C receptor is a neurochemical feature predisposing to headache. Taken together the data bring new perspectives to the role of 5-HT acting through 5-HT2C (or closely similar) receptors in the initiation of migraine.

****************

"Pathological assessment of the surgically removed valves showed noninflammatory fibrotic degeneration, hypothesized to involve the 5-HT2B serotonin receptors."

from:

Research Article
Role of COMT inhibitors and dopamine agonists in the treatment of motor fluctuations

http://www3.interscience.wiley.com/c...4918/HTMLSTART

From this reference:

Severe multivalvular heart disease: A new complication of the ergot derivative dopamine agonists:

21 May 2004

Abstract
Abstract CASE REPORTS DISCUSSION References
We report on 4 new cases of valvular heart disease in Parkinson's disease patients treated with the ergot derivative dopamine agonists pergolide and cabergoline. Noninflammatory fibrotic degeneration of cardiac valves has been reported to occur in patients with carcinoid syndrome and to occasionally complicate therapies with the anti-migraine ergot alkaloid ergotamine and methysergide and with the appetite suppressants fenfluramine and dexfenfluramine. In these cases, the pathogenesis is suspected to involve serotonin-mediated abnormal fibrogenesis by means of the 5-HT2B receptors, which are expressed in the fibroblasts of heart valves. Based on strikingly similar echocardiographic and histopathological features, we strongly suspect that ergot-derived dopamine agonists may cause a valvular heart disease nearly identical to that seen in those conditions. These cases add to a rapidly growing and worrying list of similar published reports, suggesting that we may well be facing a novel, yet unrecognized, complication of this class of agents, which are widely used not only in Parkinson's disease but also in restless legs syndrome and various common endocrine dysfunctions. Therefore, until more is known about the true prevalence of this side effect, we propose that an assessment of cardiac function be performed before and in the course of a long-term therapy with ergot derivative dopamine agonists. © 2004 Movement Disorder Society

http://www3.interscience.wiley.com/c...064/HTMLSTARTW

I read that the 5-HT2b receptor is expressed in very low levels in the human brain, and is mainly expressed in the peripheral organs. Only low expressionis found in the blood or brain. Most other serotonin receptors are found mainly in the brain (like 5-HT2c).

http://www.sciencedirect.com/science...4c5d72be404498

To Quote Paula_W...in "Update: Pergolide, Cabergoline and Heart Damage"
Quote:
See new post today: "Fast-Multiplying Lawsuits Can Stymie Medical Science, Authors Warn"