The January 4, 2007 issue of the New England Journal of Medicine includes a paper that documents a British study of more than 11,000 Parkinson's Disease patients. The study found that two ergot-derived drugs, Pergolide and Cabergoline, commonly used to treat Parkinson's Disease may increase the risk of leaky heart valves by up to 700%
"A total of 11,417 patients were included in the final cohort, all of whom had received at least two prescriptions for antiparkinsonian drugs and met all the inclusion and exclusion criteria. The mean age at entry into the study cohort was 69 years, and the mean duration of follow-up (from entry to exit from the study cohort) was 4.2 years. The numbers of patients taking dopamine agonists at any time during follow-up and the respective duration (person-years) of exposure during follow-up were as follows: 828 patients taking bromocriptine (1683 person-years), 61 taking lisuride (88 person-years), 931 taking pergolide (2031 person-years), 1228 taking cabergoline (1812 person-years), 492 taking pramipexole (648 person-years), and 993 taking ropinirole (1565 person-years). Patients may have been included in more than one of these categories of exposure because of changes in their use of dopamine agonists during follow-up. The total number of person-years of no exposure to dopamine agonists was 34,548. There were 7702 patients who were never exposed to any dopamine agonist during follow-up, accounting for 28,892 person-years. Cardiac-valve abnormalities were recorded for 81 patients in the study cohort, of whom 31 were validated as case patients with newly diagnosed cardiac-valve regurgitation.
Characteristics of 31 Case Patients with Cardiac-Valve Regurgitation, According to Use of a Dopamine Agonist. For one case patient, only 11 months of recorded data before the index date were available in the database. We included this case patient in the analysis, since the inclusion did not materially change the results of the analysis. Among the 31 case patients, 6 were currently exposed to pergolide, 6 were currently exposed to cabergoline, and 19 had no current or recent exposure to a dopamine agonist (Table 2). The resulting incidence rates of newly diagnosed cardiac-valve regurgitation were 30 per 10,000 per year for pergolide, 33 per 10,000 per year for cabergoline, and 5.5 per 10,000 per year for no exposure to any dopamine agonist.
A total of 666 controls who could be matched to the case patients were identified in the study cohort. Of these controls, 3 were excluded because of current use of multiple dopamine agonists, leaving 663 controls (Figure 1 and Table 1). The mean age of case patients and controls was 73 and 74 years, respectively. The primary diagnosis was Parkinson's disease in case patients (94%) and controls (86%). Except for current use of amantadine (Symmetrel, Endo Pharms), there was no significant difference in characteristics between case patients and controls (Table 1). Of the five case patients who were currently exposed to amantadine, three also had current exposure to cabergoline and one had current exposure to pergolide.
The rate of cardiac-valve regurgitation was elevated among patients who were currently exposed to either pergolide (adjusted incidence-rate ratio, 7.1; 95% CI, 2.3 to 22.3) or cabergoline (adjusted incidence-rate ratio, 4.9; 95% CI, 1.5 to 15.6) but not among those who were currently exposed to other dopamine agonists. For amantadine, the only concurrent medication found to have a significant association with cardiac-valve regurgitation, the adjusted incidence-rate ratio was 3.5 (95%, CI, 1.1 to 11.3). The adjusted incidence-rate ratios were particularly elevated for daily doses greater than 3 mg of pergolide (37.1; 95% CI, 5.1 to 270.6) and 3 mg of cabergoline (50.3; 95% CI, 6.6 to 381.4), as well as for a duration of use of 6 months or more.
Although current use of amantadine was the only other significant risk factor identified, the small number of case patients reduced the likelihood of the detection of additional risk factors of potential importance to the analysis. We therefore created a model that included body-mass index, smoking status, and the presence or absence of hypertension, diabetes, coronary heart disease, Parkinson's disease, restless legs syndrome, and hyperprolactinemia. In this analysis, the adjusted incidence-rate ratios were 6.0 (95% CI, 1.7 to 21.3) for pergolide and 6.9 (95% CI, 1.9 to 25.9) for cabergoline. The excess risks of cardiac-valve regurgitation for current use of pergolide and for current use of cabergoline were 33 and 21 additional case patients per 10,000 persons exposed per year, respectively. We did not have systematic clinical follow-up data on the case patients with cardiac-valve regurgitation identified in this analysis. One patient had echocardiographic evidence of regression of aortic regurgitation after discontinuation of cabergoline. Valve replacement was considered in another patient, who had been exposed to pergolide, but the procedure was not performed."
Source: ^ NEJM - Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation Study.
Reply With Quote
Originally Posted by songdog
