Cabergoline and cardiac valve disease in prolactinoma patients: additional studies during long-term treatment are required

Abstract

The increased risk of cardiac valve disease in patients treated for Parkinson's disease with cabergoline has raised concerns about the safety of treatment with ergot-derived dopamine agonists in patients with endocrine diseases, especially prolactinoma. Six cross-sectional studies have been published recently, of which five studies do not show an association between the treatment of prolactinoma with cabergoline during 45-79 months and clinically relevant valvular regurgitation in a total of 413 patients. Nonetheless, concern is raised because the use of cabergoline was associated in one study with an increased prevalence of moderate tricuspid regurgitation, and in two other studies with mild tricuspid regurgitation. Furthermore, the use of cabergoline was associated with increased frequencies of valvular thickening, calcifications and increased mitral tenting area. At present, the clinical relevance of these findings is still uncertain, but concern is raised with respect to the safety of the use of cabergoline in the long-term treatment of prolactinomas. Echocardiographic evaluation should be considered in patients, who require long-term treatment with cabergoline, especially in high doses. There is a need for larger, preferably prospective, studies with careful echocardiographic assessment and with longer durations of follow-up than the currently available studies.

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

“…The study conducted on Parkinson's disease patients reported a mean daily cabergoline dose of 3.6 mg, whereas the median weekly dose in our cohort was 1.0 mg (5). Therefore, in Parkinson's disease patients, the mean cumulative dose is far higher, 2500-6600 mg, compared with hyperprolactinemic patients (33). Identical to our results, five of eight previous publications evaluating valvular regurgitation in hyperprolactinemic patients on cabergoline therapy found no increased risk of valvular regurgitation of any grade (11,13,(15)(16)(17).…”

“…Significant evidence exists that cabergoline therapy in patients with Parkinson's disease is associated with an increased risk of developing valvular fibrosis (4,5,33). However, as mentioned before, several main differences between hyperprolactinemic and Parkinson's disease patients should be taken into account when evaluating the risks of fibrotic adverse reactions.…”

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

“…However, some important differences between the current results and our previous findings should be highlighted. In this study, median cumulative dose of CAB at both 2-year (48 mg) and 5-year evaluations (149 mg) was lower than that in our previous observation (280 mg) and much lower than that in patients with PD, usually treated with mean weekly doses up to 25 mg (7) and taking median cumulative doses ranging from 2600 to 6700 mg (8). Secondly, in our previous study (13), follow-up ranged from 16 to 250 months (median 74 months), whereas in the current prospective study, follow-up reached 60 months of observation.…”

“…In recent years, there has been an increasing recognition that ergot-derived DA, such as pergolide and cabergoline (CAB), are associated with an increased risk of cardiac valve disease in 29-39% of patients with PD (4,5,6), usually treated with mean weekly doses up to 25 mg (7) and taking median cumulative doses ranging from 2600 to 6700 mg (8), with the risk of valvular disease being significantly related to cumulative dose and treatment duration. Particularly, restrictive valvulopathy has been found in 33% of patients with PD receiving pergolide therapy, but in none of those never treated with DA (4).…”

Modern trends in diagnostics and treatment of prolactinomas

“…Îòaeå, áàãàòîð³÷íèé êë³í³÷íèé äîñâ³ä çàñòî-ñóâàííÿ ÀÄ ó ë³êóâàíí³ ïðîëàêòèíîì íå äຠïå-ðåêîíëèâèõ â³äïîâ³äåé íà òàê³ ïèòàííÿ: ÿêîþ ìຠáóòè ïî÷àòêîâà äîçà êàáåðãîë³íó, ÿê äîâãî ïîò-ð³áíî ïðîâîäèòè ë³êóâàííÿ ÀÄ àáè ïîïåðåäèòè ðèçèê ðåöèäèâó ã³ïåðïðîëàêòèíå쳿 òà ïðîãðå-ñóâàííÿ àäåíîìè, ÿê³ ð³âí³ ÏÐË ó êðîâ³ º ö³ëüî-âèìè òà ÷è º áåçïå÷íîþ äëÿ õâîðîãî òðèâàëà òåðàï³ÿ âèñîêèìè äîçàìè êàáåðãîë³íó ç îãëÿäó íà ðèçèê âèíèêíåííÿ óðàaeåíü êëàïàííîãî àïà-ðàòó ñåðöÿ [84,85,86,87]. Ñüîãîäí³ â³äñóòí³ óí³ô³êîâàí³ êðèòå𳿠ïðîãíîçóâàííÿ åôåêòèâíîñò³ òåðàﳿ ÀÄ ³ ðåöèäèâó ã³ïåðïðîëàêòèíå쳿 ï³ñëÿ ¿¿ ïðèïèíåííÿ.…”