Questioning the cardioprotective effect of bromocriptine treatment.

Bromocriptine Treatment To the Editor: I read with interest the paper “Centrally Mediated Effects of Bromocriptine on Cardiac Sympathovagal Balance” by Drs Franchi, Lazzeri, Barletta, Ianni, and Mannelli, which was published in July 2001.1 The authors cite a report by Przuntek et al2 published in 1992 that suggested that bromocriptine treatment lessened mortality in patients with Parkinson disease. The authors presumed that this putative cardioprotective effect can be related to withdrawal of cardiac sympathetic activity leading to fewer life-threatening ventricular arrhythmias. Unfortunately, the authors failed to mention that since 1992, long-term studies in Australia3 and France4 have failed to replicate the findings cited in the Przuntek paper. The Australian and French studies were of 10-year durations and found no evidence of a cardioprotective effect from bromocriptine. Over the past 25 years, bromocriptine has been studied in the treatment of clinical indications such as acromegaly, hyperprolactinemia, postpartum lactation suppression, cocaine craving, and diabetes mellitus, in addition to Parkinson disease. Rather than a cardioprotective effect, bromocriptine shares with other ergot alkaloids the property of vasoconstriction, with the potential for serious tissue injury. Hypertension5 and cardiac injury6 have been reported in association with bromocriptine use in lactation suppression. Seizures and myocardial infarction were reported in association with bromocriptine use in the treatment of cocaine craving, which led the Italian Health Ministry to request the withdrawal of bromocriptine for use in cocaine craving.7 Finally, in clinical trials of bromocriptine for the treatment of Type 2 diabetes presented to the Food and Drug Administration, a relative risk of myocardial infarction of 2.9 after bromocriptine treatment was found.8 In the design of the study by Franchi and colleagues, the investigators used single oral doses of bromocriptine with measurements at baseline and 180 minutes after bromocriptine administration. It has long been known that bromocriptine has active metabolites9 that persist in the body for up to 120 hours. Hydroxylated metabolites of bromocriptine have been found to be effective in reducing prolactin in rats.10 Dr. Franchi and colleagues did not investigate pharmacologically active bromocriptine metabolites. Finally, medical journals have recognized the need for objectivity in the publication of clinical research findings.11 In the July 2001 edition of Hypertension, 21 articles were published under the heading “Scientific Contributions.” Of these 21 articles, this paper is one of two that failed to include an acknowledgments section. One can assume that no financial, institutional, or manuscript preparation assistance was provided in support of the publication of this research. Perhaps all published papers should include an acknowledgments section with the appropriate response to allow the reader to assess the potential for conflicts of interest.