ergoline and Fibrosis

Therapy with ergot-derivative dopamine agonists (ergot-DAs) is suspected to cause or promote the development of insufficiency and regurgitation in previously normal cardiac valves. Thus, we conducted a systematic review and meta-analysis of the literature to determine whether administration of cabergoline, i.e., an ergot-DA used to treat Parkinson's disease (PD) or hyperprolactinemia, is associated with an increased risk of valve regurgitation compared with pharmacological regimens not comprising ergot-DAs or with no therapy.. Observational studies were selected from the Pubmed and Embase databases. Studies had to have assessed the prevalence, odds, or risk of cardiac valve regurgitation in patients who underwent chronic treatment with cabergoline for PD or hyperprolactinemia compared with patients with the same diseases whose therapy did not include cabergoline or another ergot-DA. Separate meta-analyses were performed for PD and hyperprolactinemia patients.. On the basis of five studies, 634 PD patients were taking cabergoline, while 9,120 PD patients were treated with dopa/dopamine decarboxylase inhibitor, alone or associated with a non-ergot DA. Valvular regurgitation of any degree - at one cardiac valve or more - was more frequent in PD patients who were taking cabergoline compared to those treated with a non-ergot DA agent or not treated with any dopamine agonist [adjusted (inverse variance: iv) odds ratio: 7.25 95 % CI: 3.71-14.18; p < 0.0001]. On the other hand, pooled data from seven studies showed that patients with hyperprolactinemia who were taking cabergoline (n = 444) exhibited significantly higher odds of mild- to-moderate tricuspid regurgitation compared to untreated controls (n = 954) [adjusted (iv) odds ratio: 1.92 95 % CI:1.34-2.73; p = 0.0003]. No significant differences in mitral or aortic valve regurgitation were detected between hyperprolactinemic patients taking cabergoline and controls.. In PD patients, the risk of valvular regurgitation of any grade involving one or more cardiac valves was proven to be strongly associated with cabergoline treatment. Furthermore, based on our results, hyperprolactinemic patients taking cabergoline have an increased risk of mild-to-moderate tricuspid valve regurgitation.

Topics: Cabergoline; Dopamine Agonists; Ergolines; Female; Fibrosis; Heart Valve Diseases; Humans; Male; Myocardium; Observational Studies as Topic; Prevalence; Risk Factors

The initial association between the development of valvular heart disease and drugs stems from observations made during the use of methysergide and ergotamine for migraine prophylaxis in the 1960s. Since then, the appetite suppressants fenfluramine and dexfenfluramine, the dopamine agonists pergolide and cabergoline, and more recently, the recreational drug ecstasy (3,4 methylenedioxymethamphetamine; MDMA) have been implicated. Results from clinical trials show that drug dose and treatment duration affect both the risk of developing the disease and its severity. The natural history of the disease remains unclear, although regression of valvular lesions after the end of treatment has been reported. Interference with serotonin metabolism and its associated receptors and transporter gene seems a likely mechanism for development of the drug-induced valvular heart disease. Physicians need to balance the benefits of continued therapy with these drugs against possible risks. Further investigation is needed to assist with treatment decisions. Continued vigilance is necessary because several commonly prescribed treatments interact with serotonergic pathways.

Topics: Antiparkinson Agents; Appetite Depressants; Cabergoline; Dexfenfluramine; Dopamine Agonists; Drug Monitoring; Ergolines; Ergotamine; Fenfluramine; Fibrosis; Heart Valve Diseases; Heart Valves; Humans; Methysergide; Migraine Disorders; N-Methyl-3,4-methylenedioxyamphetamine; Patient Selection; Pergolide; Receptors, Serotonin; Serotonin Agents; Serotonin Plasma Membrane Transport Proteins; Vasoconstrictor Agents

Fibrotic valvular heart disease (VHD) has been reported in association with ergot dopamine agonists (DAs), but the current database is insufficient regarding clinical relevance and comparison to data on non-ergot DAs. We evaluated the effects of four DAs (pergolide, cabergoline, ropinirole, pramipexole) on morphology and function of heart valves in patients with Parkinson's disease (PD) to determine the frequency and clinical relevance of DA-induced VHD. A total of 85 patients treated with ergot or non-ergot DAs and 38 age-matched controls were evaluated by transthoracic echocardiography. Valvular pathology was assessed by established criteria of valvular regurgitation and a VHD scoring system. Both grading systems revealed increased frequency of VHD in ergot DA patients compared to both non-ergot DA patients and controls with 22% of ergot DA patients having moderate VHD versus 3% of non-ergot DA patients and none of controls (P = 0.001). We did not find correlations of echocardiographic findings with duration/cumulative dose of treatment, age, or vascular risk factors. Our data suggest that ergot DAs are associated with higher prevalence of VHD compared to non-ergot DAs and controls. Standard echocardiography seems sufficient to detect VHD in PD patients treated with DAs.

Topics: Benzothiazoles; Cabergoline; Dopamine Agonists; Double-Blind Method; Echocardiography; Ergolines; Female; Fibrosis; Heart Valve Diseases; Humans; Hypertrophy, Left Ventricular; Indoles; Male; Middle Aged; Mitral Valve Insufficiency; Parkinson Disease; Pergolide; Pramipexole; Severity of Illness Index; Tricuspid Valve Insufficiency

Presently, the standard of care for prolactinomas, a type of pituitary adenoma, is dopaminergic agents such as bromocriptine and cabergoline. However, dopaminergic agents may induce fibrosis of cardiac valves leading to valvular insufficiency, necessitating surgical treatment of prolactinoma. Fibrosis of prolactinoma can be induced by prolonged medical treatment with bromocriptine, and this usually occurs after years of treatment. In comparison to bromocriptine, there have been no reports of cabergoline-induced fibrosis of prolactinoma. There is a potential for greater emphasis to be placed on assessing the tumour consistency from preoperative MRI scans, or even preoperative contrast-enhanced 3D Fast Imaging Employing Steady-state Acquisition imaging to allow better planning of the surgery. We report a rare case of fibrosis of prolactinoma after cabergoline treatment resulting in its subsequent difficult surgical removal. This patient had early MRI changes of fibrosis of prolactinoma after a short period of 6 months of cabergoline treatment.

Topics: Adult; Antineoplastic Agents; Cabergoline; Combined Modality Therapy; Diagnosis, Differential; Dopamine Agonists; Ergolines; Fibrosis; Humans; Hypogonadism; Hypothyroidism; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma; Thyroxine; Tricuspid Valve Insufficiency

In contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited.. To assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy.. Case-control study.. A transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls.. Clinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17-4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22-5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects.. Long-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.

Topics: Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Case-Control Studies; Dopamine Agonists; Echocardiography; Ergolines; Female; Fibrosis; Heart Valve Diseases; Heart Valves; Humans; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactinoma; Prospective Studies

Topics: Antiparkinson Agents; Cabergoline; Echocardiography, Doppler, Color; Ergolines; Fibrosis; Heart Valve Diseases; Heart Valves; Humans; Male; Middle Aged; Parkinson Disease

Cabergoline, a dopamine agonist used to treat hyperprolactinemia, is associated with an increased risk of fibrotic adverse reactions, e.g. cardiac valvular fibrosis, pleuropulmonary, and retroperitoneal fibrosis.. This study evaluated the prevalence and risk of fibrotic adverse reactions during cabergoline therapy in hyperprolactinemic and acromegalic patients.. A cross-sectional study was conducted in a University Hospital.. A total of 119 patients with hyperprolactinemia and acromegaly who were on cabergoline therapy participated in the study.. All patients were requested to undergo a cardiac assessment, pulmonary function test, chest X-ray, and blood tests as recommended by the European Medicine Agency. Matched controls were recruited to compare the prevalence of valvular regurgitation. Cardiac valvular fibrosis was evaluated by assessing valvular regurgitation and the mitral valve tenting area (MVTa). The risk of pleuropulmonary fibrosis was assessed by a pulmonary function test, a chest X-ray, and if indicated, by additional imaging studies.. The prevalence of clinically relevant valvular regurgitation was not significantly different between cases (11.3%) and controls (6.1%; P=0.16). The mean MVTa was 1.27+/-0.17 and 1.24+/-0.21 cm(2) respectively (P=0.54). Both valvular regurgitation and the MVTa were not related to the cumulative dose of cabergoline. A significantly decreased pulmonary function required additional imaging in seven patients. In one patient, possible early interstitial fibrotic changes were seen. Lung function impairment was not related to the cumulative cabergoline dose.. Cabergoline, typically dosed for the long-term treatment of hyperprolactinemia or acromegaly, appears not to be associated with an increased risk of fibrotic adverse events.

Topics: Acromegaly; Blood Sedimentation; C-Reactive Protein; Cabergoline; Creatinine; Cross-Sectional Studies; Dopamine Agonists; Echocardiography; Electrocardiography; Ergolines; Female; Fibrosis; Glomerular Filtration Rate; Heart Valve Diseases; Heart Valves; Humans; Hyperprolactinemia; Lung; Lung Diseases; Male; Middle Aged; Respiratory Function Tests; Retroperitoneal Fibrosis; Statistics, Nonparametric

There is growing evidence that the ergot-derived dopamine agonists cabergoline and pergolide can cause fibrotic cardiac valvulopathy. Data on other fibrotic reactions and nonergot-derived dopamine agonists are sparse. Aim of this study was to investigate whether there are signals that dopamine agonists are related to cardiac and other fibrotic reactions. We identified all reports of fibrotic reactions at the heart, lung, and retroperitoneal space associated with dopamine agonists within the US Adverse Event Reporting System database. Disproportionality analyses were used to calculate adjusted reporting odds ratios (RORs). For ergot-derived dopamine agonists (bromocriptine, cabergoline, pergolide), the RORs of all reactions under study were increased, whereas no such increases were observed for nonergot-derived drugs (apomorphine, pramipexole, ropinirole, rotigotine). Fibrotic reactions due to ergot-derived dopamine agonists may not be limited to heart valves. For nonergot-derived dopamine agonists, no drug safety signals were evident.

Topics: Aged; Aged, 80 and over; Apomorphine; Benzothiazoles; Bromocriptine; Cabergoline; Databases, Factual; Dopamine Agonists; Endomyocardial Fibrosis; Ergolines; Female; Fibrosis; Heart Valve Diseases; Humans; Indoles; Male; Middle Aged; Pergolide; Pericarditis; Pleural Diseases; Pramipexole; Pulmonary Fibrosis; Retroperitoneal Fibrosis; Tetrahydronaphthalenes; Thiophenes; United States

Topics: Brain Ischemia; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Fatal Outcome; Fibrosis; Heart Valve Prosthesis Implantation; Humans; Intestinal Obstruction; Male; Middle Aged; Mitral Valve Insufficiency; Pituitary Neoplasms; Prolactinoma; Tricuspid Valve Insufficiency; Ventricular Dysfunction, Left

Cardiac valvulopathy has been recently associated with the use of the ergot dopamine agonist (EDA) pergolide in Parkinson's disease (PD). Cabergoline a widely used, well-tolerated EDA which has also been recently implicated in relation to fibrotic side effects although the evidence base for this is not sound.. In PD patients on chronic cabergoline therapy, do symptoms suggestive of serosal/cardiac fibrosis imply underlying fibrotic lesions?. A retrospective data review of 234 PD cases from three UK centres, on chronic cabergoline monotherapy or adjunctive treatment to identify symptoms suggestive of pleuro-pulmonary, cardiac or retroperitoneal fibrosis. These causes were thereafter selectively examined by appropriate specialists with relevant investigations.. Out of 234 cases, 15 were identified with symptoms suggestive of respiratory, cardiac or abdominal systems involvement although subsequent investigations failed to reveal definite association with cabergoline except two cases with probable alveolitis and a possible association with cardiac murmur in one case. In spite of the deficiencies of a retrospective study, the results suggest a low risk of fibrotic side effects with cabergoline, particularly cardiac valvulopathy.

Topics: Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Cabergoline; Ergolines; Female; Fibrosis; Heart Valve Diseases; Humans; Male; Middle Aged; Parkinson Disease; Pulmonary Fibrosis; Retroperitoneal Fibrosis; Retrospective Studies

A 63 year old man with a six year history of Parkinson's disease presented with signs of right heart failure following a knee replacement. Constrictive pericarditis was diagnosed and a radical pericardectomy performed. Six months later, the patient remained unwell with raised inflammatory markers. An inflammatory fibrotic reaction caused by cabergoline was diagnosed. He improved after cessation of cabergoline.

Topics: Antiparkinson Agents; Cabergoline; Ergolines; Fibrosis; Humans; Male; Middle Aged; Parkinson Disease; Pericarditis, Constrictive; Pleura; Pulmonary Fibrosis

Topics: Aortic Valve; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Fibrosis; Heart Valve Diseases; Humans; Parkinson Disease; Pergolide