Absence of major fibrotic adverse events in hyperprolactinemic patients treated with cabergoline

Abstract

Background: Cabergoline, a dopamine agonist used to treat hyperprolactinemia, is associated with an increased risk of fibrotic adverse reactions, e.g. cardiac valvular fibrosis, pleuropulmonary, and retroperitoneal fibrosis. Objective: This study evaluated the prevalence and risk of fibrotic adverse reactions during cabergoline therapy in hyperprolactinemic and acromegalic patients. Design: A cross-sectional study was conducted in a University Hospital. Patients: A total of 119 patients with hyperprolactinemia and acromegaly who were on cabergoline therapy participated in the study. Methods: All patients were requested to undergo a cardiac assessment, pulmonary function test, chest X-ray, and blood tests as recommended by the European Medicine Agency. Matched controls were recruited to compare the prevalence of valvular regurgitation. Cardiac valvular fibrosis was evaluated by assessing valvular regurgitation and the mitral valve tenting area (MVTa). The risk of pleuropulmonary fibrosis was assessed by a pulmonary function test, a chest X-ray, and if indicated, by additional imaging studies. Results: The prevalence of clinically relevant valvular regurgitation was not significantly different between cases (11.3%) and controls (6.1%; PZ0.16). The mean MVTa was 1.27G0.17 and 1.24G0.21 cm 2 respectively (PZ0.54). Both valvular regurgitation and the MVTa were not related to the cumulative dose of cabergoline. A significantly decreased pulmonary function required additional imaging in seven patients. In one patient, possible early interstitial fibrotic changes were seen. Lung function impairment was not related to the cumulative cabergoline dose. Conclusion: Cabergoline, typically dosed for the long-term treatment of hyperprolactinemia or acromegaly, appears not to be associated with an increased risk of fibrotic adverse events.

Prospective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia

“…In consequence, our subjects treated with long-term cabergoline therapy did not have a statistically significantly increased risk of clinically relevant cardiac valve disease. These results are concordant with most other studies [24][25][26][27][28][29][30]. Only one study found significant tricuspid valve regurgitation in patients receiving high cumulative doses of cabergoline [31].…”

Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment

“…A clear linear dose and duration dependency of fibrotic valvular disease was found in Parkinsonian patients who are usually treated with approximately tenfold higher doses than the prolactinoma patients (6,22). In contrast, results of the previous studies in prolactinoma patients are controversial, but most of them reported no linear relation between the severity of valvular lesions and cumulative dose (23,24,25,26,27,28). We could, therefore, suggest that the dose-response relationship may be different in low-and high-dose regimens.…”

“…Results from ten observational studies investigating the risk of fibrotic valvulopathy in cabergoline-treated patients have been published to date (23,24,25,26,27,28,29,30,31,32). Five of them have shown no relevant findings (24,25,27,29,30).…”

“…Five of them have shown no relevant findings (24,25,27,29,30). Four trials have demonstrated an increased prevalence of clinically insignificant valvular changes such as mild tricuspid regurgitation (23,28,32), pulmonic regurgitation (32), aortic calcification (28), and an increased mitral tenting area (26).…”

Transforming growth factor β1 is not a reliable biomarker for valvular fibrosis but could be a potential serum marker for invasiveness of prolactinomas (pilot study)

“…Cabergoline, which possesses a complete 5HT 2b agonistic activity, is the drug of choice in the treatment of prolactinomas, but the results of observational studies investigating the risk of FVHD in these patients are still controversial. Some of them have reported no relevant findings (8,9,10,11,12), five trials have observed clinically insignificant valvular changes (13,14,15,16,17), and only one study has reported an increased prevalence of moderate tricuspid regurgitation with a cumulative dose-dependent risk (18). Published data on the potential profibrotic effect of bromocriptine, a partial 5HT 2b agonist, are exclusively limited (19).…”