Dopamine agonists, which are first-line drugs for treating Parkinson’s disease and also are used to treat restless legs syndrome, reportedly may be associated with fibrotic heart valve disease. Pergolide has been implicated, but there is reason to believe that not all dopamine agonists pose a risk. Unlike other drugs of this class, pergolide and cabergoline are strong agonists of the 5-hydroxytryptamine 2B receptor expressed on heart valves.
The investigators used data from the United Kingdom General Practice Research Database to form a population-based cohort of 11,417 individuals 40 to 80 years of age who, in the years 1988–2005, were prescribed anti-Parkinsonian drugs. In a nested case–control analysis, each patient with newly diagnosed cardiac valve regurgitation was matched with up to 25 control subjects for age, gender, and year of entry into the cohort. In addition to pergolide and cabergoline, patients variably received the dopamine agonists bromocriptine, lisuride, pramipexole, and ropinirole. Incidence-rate ratios for heart valve regurgitation were estimated by conditional logistic regression analysis.
Patients in the study cohort had a mean age at entry of 69 years and were followed for an average of 4.2 years. Thirty-one case patients had newly diagnosed cardiac valve regurgitation. Six each were currently receiving pergolide and cabergoline, whereas the remaining 19 had not received any dopamine agonist within the previous year. The incidence-rate ratio associated with the current use of pergolide was 7.1, with a 95% confidence interval of 2.3–22.3. The respective figures for cabergoline were 4.9 and 1.5–15.6. There was no indication that the risk of valve regurgitation was increased by the current use of other dopamine agonists. A particularly close association was evident when daily doses exceeded 3 mg of either pergolide or cabergoline, and the risk also was increased when either of these drugs was used for 6 months or longer. The only other significant risk factor was current use of amantadine. When adjusting for body mass index, smoking status, and the presence or absence of coronary heart disease, hypertension, diabetes, Parkinson’s disease, restless legs syndrome, and hyperprolactinemia, incidence-rate ratios for pergolide and cabergoline were 6.0 and 6.9, respectively. The respective excess risk figures were 33 and 21 additional case patients for every 10,000 persons exposed per year.
In this large-scale cohort study, current use of either pergolide or cabergoline was associated with a considerably increased risk of newly diagnosed heart valve regurgitation. No such association was found for other dopamine agonists, The increase in risk may actually have been underestimated because not all patients were monitored echocardiographically.
Department of Clinical Pharmacology, Charité Campus Mitte, and Department of Cardiology, Charité Campus Virchow, Charité-Universitätsmedzin Berlin, Berlin; and McGill Pharmacoepidemiology Research Unit, Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University Health Centre, Montreal
N Engl J Med 2007;356:29–38