A Follow-Up Study of the Prevalence of Valvular Heart Abnormalities in Hyperprolactinemic Patients Treated With Cabergoline

Abstract

This large UK follow-up study does not support a clinically significant association between the use of DA for the treatment of hyperprolactinemia and cardiac valvulopathy.

Cabergoline for hyperprolactinemia: getting to the heart of it

“…The mean cumulative dose in the study by Vroonen L et al was 277.8 mg, interquartile range (IQR) 121.4-427.8 [18], similar to another recent prospective study in which cumulative dose was 232 mg, with IQR 91-551 mg [17], less than one tenth of the mean cumulative dose associated clinically significant valulopathy in men with Parkinson's [1]. The absence of a significant association with cumulative dose of cabergoline among the few hyperprolactinemic patients who developed valvular dysfunction [17,18], may be due to the fact that the sample size was too small to show this and/or that the cumulative dose was lower than the threshold dose required to see this association. Of note in the prospective study by Drake et al among 192 patients, even though a significant association of cumulative dose and valvular insufficiency was not found, four of the five patients who had interval progression to grade 3 (moderate) had received a cumulative dose of cabergoline higher than the mean, and in three of these cumulative dose was >1000 mg.…”

“…The cumulative dose reached after many years in patients treated with cabergoline for prolactin disorders does not nearly approach the critical threshold reported in the studies of Parkinson's patients, in which cumulative doses averaged >2 g (mean was 2820 mg with standard deviation (SD) of 2515 mg) in the group with trace or mild valvular regurgitation and >4 g (mean was 4015 mg with SD of 3208 mg) in those with clinically significant disease (moderate or severe regurgitation) [1]. The mean cumulative dose in the study by Vroonen L et al was 277.8 mg, interquartile range (IQR) 121.4-427.8 [18], similar to another recent prospective study in which cumulative dose was 232 mg, with IQR 91-551 mg [17], less than one tenth of the mean cumulative dose associated clinically significant valulopathy in men with Parkinson's [1]. The absence of a significant association with cumulative dose of cabergoline among the few hyperprolactinemic patients who developed valvular dysfunction [17,18], may be due to the fact that the sample size was too small to show this and/or that the cumulative dose was lower than the threshold dose required to see this association.…”

“…None reported clinically significant valvular heart disease [8][9][10][11][12][13][14][15] with the single exception in a cohort with a high rate of background hypertension [7] and for which the prospective follow up of this cohort receiving ongoing cabergoline therapy, failed to show progressive * Lisa B. Nachtigall lnachtigall@mgh.harvard.edu disease [16]. While the preliminary cross-sectional data were essentially negative, including mean cumulative doses in these studies that ranged from 146-443 mg [7][8][9][10][11][12][13][14][15], long term randomized prospective studies have recently become available [16][17][18] and the one by Vroonen et al in this issue is the longest in duration with a median interval between echocardiograms of 62.5 months and a median total duration of therapy with cabergoline of 124.5 months, and this study was unique, among the prospective studies, by virtue of the inclusion a control group of non cardiac patients at baseline [18]. The prospective randomized controlled study by Vroonen et al from CHU Liège in Belgium, reported in this issue of Endocrine, is reassuring in the lack of clinically relevant valvular heart disease seen in pituitary patients treated with typical doses of dopamine agonists [18] and confirms similar findings among patients with prolactin disorders prospectively evaluated [16,17] as well as a prior prospective study among patients treated for acromegaly [19].…”

“…While the preliminary cross-sectional data were essentially negative, including mean cumulative doses in these studies that ranged from 146-443 mg [7][8][9][10][11][12][13][14][15], long term randomized prospective studies have recently become available [16][17][18] and the one by Vroonen et al in this issue is the longest in duration with a median interval between echocardiograms of 62.5 months and a median total duration of therapy with cabergoline of 124.5 months, and this study was unique, among the prospective studies, by virtue of the inclusion a control group of non cardiac patients at baseline [18]. The prospective randomized controlled study by Vroonen et al from CHU Liège in Belgium, reported in this issue of Endocrine, is reassuring in the lack of clinically relevant valvular heart disease seen in pituitary patients treated with typical doses of dopamine agonists [18] and confirms similar findings among patients with prolactin disorders prospectively evaluated [16,17] as well as a prior prospective study among patients treated for acromegaly [19]. Given the bulk of data, including the many cross sectional studies and the newly reported perspective studies in patients with prolactin disorders treated with cabergoline, it is not unreasonable to consider baseline echocardiography in patients in whom chronic treatment with cabergoline is planned but to reserve mandating ongoing follow up echocardiography to those with the following: (1) baseline echocardiogram demonstrating significant abnormalities, (2) increased risk of valvular disease, (3) signs or symptoms of valvular disease, (4) high cumulative doses of cabergoline (those who receive higher doses and/or very long duration of therapy).…”

Recent Progress in the Medical Therapy of Pituitary Tumors

“…Higher doses may induce cardiac valvular abnormalities by a serotonin-mediated stimulatory effect on fibroblasts [48]. Recent prospective studies did not show a clear association with smaller doses [50], but should be monitored on cabergoline doses >2 mg/week [46]. Overall, 10% of patients will remain DA resistant and will require surgery, which can also be considered for patients intolerant to medication or with larger tumors pre-pregnancy.…”