A comparison of cabergoline and bromocriptine on the risk of valvular heart disease in patients with prolactinomas

Abstract

Therapy with dopamine agonists has been associated with valvular heart disease (VHD) in Parkinson's disease, raising concern about the safety of these drugs. In hyperprolactinemic patients, the studies have mainly focused on the cardiac effects of cabergoline (CBG), with little information on bromocriptine (BRC). The aim of the present study was to evaluate the prevalence of VHD in patients with prolactinomas treated with CBG and BRC. The CBG group consisted of 51 patients (37 female; age 42.3 ± 13.5 years) who had been taking CBG for at least 1 year (mean 37.8 ± 21.3 months; cumulative doses 16-1,286.8 mg). The BRC group consisted of 19 patients (14 female; age 41.8 ± 11.5 years) who were on BRC for at least 1 year (mean 54.8 ± 30.2 months; cumulative doses 4,687.5-23,478.8 mg). The controls (CTR) were 59 healthy subjects matched for age, sex, and prevalence of arterial hypertension. Participants were subjected to transthoracic echocardiography and the valvular regurgitation was graduated as absent (grade 0), trace (1), mild (2), moderate (3) or severe (4). Compared to CTR, trace mitral (Mi) regurgitation (49% vs. 27.1%; P = 0.02), trace tricuspid (Tri) regurgitation (45.1% vs. 20.3%; P = 0.0003) and mild Tri regurgitation (7.8% vs. 0%; P = 0.0003) were more prevalent with CBG, while trace Tri regurgitation (73.7% vs. 20.3%; P = 0.0004) were more prevalent with BRC. Mitral tenting area was significantly higher in CBG than in BRC and CTR. None of the valvar abnormalities was associated with symptoms. In conclusion, patients with prolactinomas treated with either CBG or BRC showed higher prevalence of trace and mild Tri or Mi regurgitation, but these findings were not clinically significant.

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

“…Results from 15 observational studies investigating the risk of fibrotic valvulopathy in hyperprolactinemic patients treated with CAB have been published to date (13,14,15,16,17,18,19,20,21,22,23,24,25,26,27). Two of them (15,20) have shown no relevant findings.…”

“…Four studies (16,18,21,24) have demonstrated an increased prevalence of non-clinically relevant valve regurgitations, including mild tricuspid regurgitation (16,21,24), pulmonic insufficiency (16), or enlarged mitral tenting area (18). Ten trials (13,14,17,18,19,22,23,25,26,27) have reported a variable prevalence, ranging from 2% (25) to 54% (13), of relevant valvulopathy including moderate-to-severe mitral or tricuspid insufficiency and mild aortic regurgitation, with the latter being observed only in two investigations (22,24). Overall, a median CRVD rate of w4% has been reported in hyperprolactinemic patients receiving treatment with CAB.…”

“…Over the past 5 years, 15 independent studies (13,14,15,16,17,18,19,20,21,22,23,24,25,26,27) (Table 1) have investigated the effects of CAB on the development of CRVD in patients with prolactinomas. Overall, these studies have reported a median CRVD rate of w4%, with the prevalence of CRVD ranging from 54% (13), 40% (24), 15% (17) to 0% (15,16,19,21) and valvulopathy being assessed according to the International Guidelines suggested by the American Society of Echocardiography (28,29) in all studies and also according to the European Association of Echocardiography (30,31) in ten studies (13,16,17,18,20,22,23,25,26,27). Moreover, a significant correlation between cumulative dose of CAB and prevalence of valve disease has been demonstrated in only two reports (13,24), whereas the vast majority of studies have agreed on safety of treatment with CAB on valvulopathy in hyperprolactinemic patients.…”

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

“…Regarding cabergoline use in the endocrine setting, they did find a trend to develop mild to moderate valve regurgitation. In their analysis, they included seven studies [13,24,26,31,32,39,40] comparing data of 444 treated cases versus 954 controls. They conclude that although globally safe, a periodic ultrasound assessment should not be avoided even if cabergoline dose is low.…”

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)

“…Published data on the potential profibrotic effect of bromocriptine, a partial 5HT 2b agonist, are exclusively limited (19). Although there are numerous case reports in the literature, only a few studies have been dedicated to this topic (13,17,20,21). As drug-induced valvulopathy in Parkinsonian patients has been shown to be a cumulative dosedependent process, for potentially at-risk groups, not only patients receiving high daily doses, but also those on low-dose long-term treatment, such as patients with invasive macroprolactinomas who are often on lifelong therapy, should be considered.…”