A Cross-Sectional Study of the Prevalence of Cardiac Valvular Abnormalities in Hyperprolactinemic Patients Treated With Ergot-Derived Dopamine Agonists

Drake, William M; Stiles, Craig E; Howlett, Trevor A.; Toogood, Andrew; Bevan, J. S.; Steeds, Richard P.

doi:10.1210/jc.2013-2254

Cited by 57 publications

(31 citation statements)

References 21 publications

(44 reference statements)

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“…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].…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2016

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Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as it permits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated in Parkinson's disease patients treated with dopamine agonists. Retrospective studies in prolactinoma patients treated with cabergoline at lower doses did not show such an effect. However, few prospective data with long-term follow-up are available. The aim of this study was to assess the safety of cabergoline regarding cardiac valvular status during prospective follow-up in patients treated for prolactinoma or idiopathic hyperprolactinemia. We report here a series of 100 patients (71F; median age at diagnosis: 41.5 years) treated with cabergoline for endocrine diseases (prolactinoma n = 89, idiopathic hyperprolactinemia n = 11). All patients underwent complete transthoracic echocardiographic studies at baseline and during long-term prospective surveillance using the same equipment and performed by the same technicians. The median interval between baseline and last follow-up echocardiographic studies while on cabergoline was 62.5 months (interquartile range: 34.75-77.0). The median total duration of cabergoline treatment was 124.5 months (interquartile range: 80.75-188.75) and the median cumulative total dose of cabergoline was 277.8 mg (interquartile range :121.4-437.8 mg) at last follow-up. We found no clinically relevant alterations in cardiac valve function or valvular calcifications with cabergoline treatment. Our data suggest that findings from retrospective analyses are correct and that cabergoline is a safe chronic treatment at the doses used typically in endocrinology.

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Section: Discussionsupporting

confidence: 90%

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

et al. 2016

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“…Moreover, none of the studies evaluating a relationship between bromocriptine exposure and valvular heart disease in prolactinoma subjects demonstrated any clinically significant valvular disease [200][201][202]. In hyperprolactinemia patients treated with bromocriptine up to a cumulative dose of 40 g, there was no increased relative risk of valvular heart disease [203]. The therapeutic dose of bromocriptine-QR used in treatment of type 2 diabetes is between 1.6 and 4.8 mg/day and is lower than bromocriptine doses typically used to treat hyperprolactinemia (5-15 mg/day) or Parkinson's disease (10-50 mg/day).…”

Section: Clinical Use and Treatment Considerations Summarymentioning

confidence: 99%

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary

Raskin

Cincotta

2016

Expert Review of Endocrinology & Metabolism

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An extended series of studies indicate that endogenous phase shifts in circadian neuronal input signaling to the biological clock system centered within the hypothalamic suprachiasmatic nucleus (SCN) facilitates shifts in metabolic status. In particular, a diminution of the circadian peak in dopaminergic input to the peri-SCN facilitates the onset of fattening, insulin resistance and glucose intolerance while reversal of low circadian peak dopaminergic activity to the peri-SCN via direct timed dopamine administration to this area normalizes the obese, insulin resistant, glucose intolerant state in high fat fed animals. Systemic circadian-timed daily administration of a potent dopamine D2 receptor agonist, bromocriptine, to increase diminished circadian peak dopaminergic hypothalamic activity across a wide variety of animal models of metabolic syndrome and type 2 diabetes mellitus (T2DM) results in improvements in the obese, insulin resistant, glucose intolerant condition by improving hypothalamic fuel sensing and reducing insulin resistance, elevated sympathetic tone, and leptin resistance. A circadian-timed (within 2 hours of waking in the morning) once daily administration of a quick release formulation of bromocriptine (bromocriptine-QR) has been approved for the treatment of T2DM by the U.S. Food and Drug Administration. Clinical studies with such bromocriptine-QR therapy (1.6 to 4.8 mg/day) indicate that it improves glycemic control by reducing postprandial glucose levels without raising plasma insulin. Across studies of various T2DM populations, bromocriptine-QR has been demonstrated to reduce HbA1c by -0.5 to -1.7. The drug has a good safety profile with transient mild to moderate nausea, headache and dizziness as the most frequent adverse events noted with the medication. In a large randomized clinical study of T2DM subjects, bromocriptine-QR exposure was associated with a 42% hazard ratio reduction of a pre-specified adverse cardiovascular endpoint including myocardial infarction, stroke, hospitalization for congestive heart failure, revascularization surgery, or unstable angina. Bromocriptine-QR represents a novel method of treating T2DM that may have benefits for cardiovascular disease as well. ARTICLE HISTORY

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“…However, it is important to emphasize that in this critical analysis, there was a high heterogeneity of studies and in many studies there was pre-selection of patients. The control rates in prospective clinical trials and in ''real life'' data from reference centers are lower [9][10][11][12][13]. In the prospective multicenter studies with both octreotide LAR and lanreotide autogel, biochemical control of acromegaly was obtained in about 30 % of the patients, and tumor shrinkage was observed in *75 % of the patients [10,11].…”

Section: Cabergoline As a Monotherapymentioning

confidence: 99%

“…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].…”

Section: Side Effectsmentioning

confidence: 99%

Cabergoline treatment in acromegaly: cons

Kasuki

Neto

2014

Endocrine

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Many options are available for the treatment of acromegaly, including surgery, radiotherapy, and medical treatment. Cabergoline (CAB), a dopamine agonist with high affinity for dopamine receptor type 2, has been used both in monotherapy and in conjunction with somatostatin analogs (SSAs). Although it is administered orally and has a relatively lower-cost in comparison with SSAs, few studies have demonstrated its usefulness, there is a lack of randomized-controlled trials and other drugs (SSAs and pegvisomant) with more data in the literature are available; these issues are the main drawbacks of adopting CAB for the treatment of acromegaly.

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A Cross-Sectional Study of the Prevalence of Cardiac Valvular Abnormalities in Hyperprolactinemic Patients Treated With Ergot-Derived Dopamine Agonists

Abstract: This large UK cross-sectional study does not support a clinically concerning association between the use of dopamine agonists for the treatment of hyperprolactinemia and cardiac valvulopathy.

Cited by 57 publications

References 21 publications

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

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

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary

Cabergoline treatment in acromegaly: cons

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