Safety of long-term treatment with cabergoline on cardiac valve disease in patients with prolactinomas

Abstract

Objective: Cabergoline (CAB) has been found to be associated with increased risk of cardiac valve regurgitation in Parkinson's disease, whereas several retrospective analyses failed to detect a similar relation in hyperprolactinemic patients. The current study aimed at investigating cardiac valve disease before and after 24 and 60 months of continuous treatment with CAB only in patients with hyperprolactinemia. Subjects and methods: Forty patients (11 men and 29 women, aged 38.7G12.5 years) newly diagnosed with hyperprolactinemia entered the study. Cumulative CAB dose ranged from 12 to 588 mg (median 48 mg) at 24 months and 48-1260 mg (median 149 mg) at 60 months. All patients underwent a complete trans-thoracic echocardiographic examination. Valve regurgitation was assessed according to the American Society of Echocardiography. Results: At baseline, the prevalence of trace mitral, aortic, pulmonic, and tricuspid regurgitations was 20, 2.5, 10, and 40% respectively, with no patient showing clinically relevant valvulopathy. After 24 months, no change in the prevalence of trace mitral (PZ0.78) and pulmonic (PZ0.89) regurgitations and of mild aortic (PZ0.89) and tricuspid (PZ0.89) regurgitations was found when compared with baseline. After 60 months, the prevalence of trace tricuspid regurgitation was only slightly increased when compared with that after 24 months (37.5%; PZ0.82), but none of the patients developed significant valvulopathy. No correlation was found between cumulative dose and prevalence or grade of valve regurgitation at both evaluations. Prolactin levels normalized in all patients but one. Conclusion: CAB does not increase the risk of significant cardiac valve regurgitation in prolactinomas after the first 5 years of treatment.

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

“…Follow-up was at least one year, but the median follow-up was much longer, at nearly 10 years and the cumulative median dose of cabergoline was >277 mg. None of the handful of moderate mitral or tricuspid regurgitation cases noted at baseline worsened significantly during follow-up. These results are in keeping with other data from prospective analyses [33][34][35]; however, in contrast to Delgado et al, we did not identify any cases of significant calcification despite similar mean ages at diagnosis in the two studies. Many factors can influence valvular calcifications (dyslipidemia, age, hypertension, renal failure, hyperphosphatemia) and discrepancies between studies might be explained by differences in the populations studied.…”

Cabergoline treatment in acromegaly: cons

“…This medication was discontinued for the treatment of Parkinson's disease; however, because the dose used in the treatment of pituitary adenomas is much lower, the drug continued to be used in this setting. Subsequently, there were several studies addressing the risk of valvar damage in prolactinoma and acromegaly patients, without clear evidence of clinically significant valvar disease [12,[40][41][42]. The majority of the studies evaluated patients treated for hyperprolactinemia, and the follow-up times were short to assure that CAB was not associated with a risk for valvar disease in the doses used in acromegaly treatment [40,41,43,44].…”

MANAGEMENT OF ENDOCRINE DISEASE: GH excess: diagnosis and medical therapy

“…However, a large register study of Parkinson's disease carried out in 2007 has documented an increased risk of valvulopathy in patients treated with a cabergoline dose higher than 3 mg/day (93), and Zanettini et al (94) reported an association between cumulated doses of cabergoline and valvulopathy. From 2008 to the present, 16 clinical studies have been published on dopamine agonists -primarily cabergoline -and valvulopathy in patients with hyperprolactinaemia (95). The conclusions from these clinical studies were reassuring, and a register study found no association between clinically significant cardiac valve disease and cabergoline therapy in patients with hyperprolactinaemia (96).…”