Do certain dopamine agonists increase the risk of heart valve damage?

The risk of cardiac valve damage is elevated in patients taking pergolide (Permax) or cabergoline (Dostinex), especially if the dose is higher than 3 mg per day and the drug is taken for more than 6 months. The absolute risk is modest: approximately 2.5 additional cases of valve damage for every 1000 patients who take one of the drugs for 1 year. (LOE = 3b)

Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med 2007;356:29-38.  [PMID:17202453]

Case-control

Industry

Outpatient (primary care)

The dopamine agonists pergolide and cabergoline interact with 5-hydroxytryptamine 2B receptors on cardiac valves, and there have been case reports of valve damage in patients taking these drugs for treatment of Parkinson's disease or restless leg syndrome. This was a case-control study nested inside of a large cohort study of primary care patients; the researchers used the General Practice Research Database, which includes data on more than 6 million patients in 350 British general practices. The database tracks medication use, diagnoses, physician encounters, and patient demographics. Patients were included in this study if they were between the ages of 40 years and 80 years and had received at least 2 prescriptions for levodopa, selegiline, bromocriptine, cabergoline, pergolide, lisuride, pramipexole, or ropinirole between 1988 and 1995. Patients were excluded if they had a history of heart valve damage, had taken medications suspected of causing heart valve damage, or had a condition like cardiomyopathy or heart failure associated with heart valve damage. Patients were followed up until they died, developed valve damage, or met one of the study exclusion criteria. Of 11,417 patients who met the inclusion criteria, 81 developed possible new valvular regurgitation; of which 31 were confirmed by a review of records by independent, blinded cardiologists. These 31 cases were each matched with 25 control patients by sex, age, and time that they entered the study. All had to have at least 12 months of prescription data and no myocardial infarction within the past 3 years. The average patient was 69 years old and was followed up for 4.2 years. The most common drug used was levodopa, used by 75% of the patients and control patients. Valve regurgitation was more common among patients taking pergolide (adjusted incidence ratio [AIR] = 7.1; 95% CI, 2.3 - 22.3) and cabergoline (AIR = 4.9; 1.5 - 15.6) than in those not taking a dopamine agonist. There was a small increase in risk with amantadine (AIR = 3.5; 1.1 - 11.3). Risk was especially high in patients taking doses higher than 3 mg or more of either drug (AIR = 37.1 for pergolide; AIR = 50.3 for cabergoline). All patients with valve damage attributed to one of these drugs had used the drug for at least 6 months. It is important to note that although the relative risks are relatively high, valve damage is still a rare complication in absolute terms, occurring in 30 patients per 10,000 per year taking pergolide compared with 5.5 patients per 10,000 per year for control patients.