ergoline and Heart-Valve-Diseases

Present recommendations by the US Food and Drug Administration advise that patients with prolactinoma treated with cabergoline should have an annual echocardiogram to screen for valvular heart disease. Here, we present new clinical data and a systematic review of the scientific literature showing that the prevalence of cabergoline-associated valvulopathy is very low. We prospectively assessed 40 patients with prolactinoma taking cabergoline. Cardiovascular examination before echocardiography detected an audible systolic murmur in 10% of cases (all were functional murmurs), and no clinically significant valvular lesion was shown on echocardiogram in the 90% of patients without a murmur. Our systematic review identified 21 studies that assessed the presence of valvular abnormalities in patients with prolactinoma treated with cabergoline. Including our new clinical data, only two (0·11%) of 1811 patients were confirmed to have cabergoline-associated valvulopathy (three [0·17%] if possible cases were included). The probability of clinically significant valvular heart disease is low in the absence of a murmur. On the basis of these findings, we challenge the present recommendations to do routine echocardiography in all patients taking cabergoline for prolactinoma every 12 months. We propose that such patients should be screened by a clinical cardiovascular examination and that echocardiogram should be reserved for those patients with an audible murmur, those treated for more than 5 years at a dose of more than 3 mg per week, or those who maintain cabergoline treatment after the age of 50 years.

Topics: Adult; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma

Cabergoline (CAB) is widely used for the medical treatment of pituitary tumors, particularly those associated with hormone hypersecretion. Whether treatment with CAB is associated with an increased risk of clinically relevant cardiac valve disease in patients with pituitary tumors is still debated. In most studies, CAB has been found not associated with an increased risk of significant valvulopathy, and no correlation has been shown between valvular abnormalities and CAB duration or cumulative dose. This review provides an overview of the studies reporting on the outcome of CAB in terms of cardiac valve disease in patients with pituitary tumors.

Topics: Acromegaly; Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Pituitary Neoplasms; Prolactinoma

Treatment with dopamin agonists, particularly cabergoline, is the primary and preferred therapy for prolactinomas and symptomatic hyperprolactinaemia due to its effectiveness and tolerability. However, an association has been demonstrated between fibrotic heart valve disease and high-dose dopamin agonist use in patients with Parkinson's disease in several echocardiographic studies. Such observations have prompted a number of studies of valvular function in cabergoline-treated hyperprolactinaemia patients. These studies have failed to show an increased prevalence of clinically significant valvular regurgitation.

Topics: Antiparkinson Agents; Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Hyperprolactinemia; Parkinson Disease; Ultrasonography

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

Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson's disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate management.

Topics: Dopamine Agonists; Ergolines; Global Health; Heart Valve Diseases; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Parkinson Disease; Prevalence; Serotonin Agents

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

High-dose cabergoline therapy has been related to cardiac valve regurgitation in patients with Parkinson's disease.. To perform a systematic analysis of reports on low-dose cabergoline treatment in hyperprolactinemia and its effect on the cardiac valves.. None of the seven reports analyzed, including 463 patients in total, found clinically significant valve regurgitation. Only one report found moderate tricuspid valve regurgitation, and other two reports found mild tricuspid valve regurgitation. An increase in the mitral tenting area was documented in only one of two reports. Valve thickening and calcifications were found in only one study.. Cabergoline seems to be safe at the doses employed in hyperprolactinemic patients. There is a higher prevalence of tricuspid regurgitation, detected by systematic echocardiography, but this abnormality is asymptomatic. Although prospective longitudinal studies are needed, vigilance of these patients is recommended, especially those treated with high-dose cabergoline.

Topics: Adult; Aged; Antiparkinson Agents; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactin; Prolactinoma; Ultrasonography

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.

Topics: Cabergoline; Clinical Trials as Topic; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Pituitary Neoplasms; Prolactinoma

Dopamine agonists have been associated with increased risk of cardiac valve regurgitation in patients with Parkinson's disease. Whether these drugs might be harmful for patients with hyperprolactinemia is still unsettled. Occasional case reports and 7 studies on the relationship between cabergoline and cardiac valve regurgitation have been published so far. Overall, cabergoline has been considered a safe therapy, although some studies suggested an increased prevalence of cardiac valve regurgitation. The aim of this meta-analysis was to assess the effects of cabergoline on cardiac valve regurgitation. Eligible studies were all trials using cabergoline in patients with either tumor or non-tumor hyperprolactinemia. Our search was updated to October 2008. Pooled data from the 6 selected studies showed that treatment with cabergoline was associated with increased risk of tricuspid valve regurgitation (fixed effects: prevalence ratio=1.40; 95% confidence interval: 1.17-1.67); on the contrary, patients treated with cabergoline and control subjects did not differ in prevalence of aortic or mitral valve regurgitation. This meta-analysis shows that patients with hyperprolactinemia treated with cabergoline are at increased risk of regurgitation of the tricuspid valve. However, regurgitation was only an echocardiographic finding since no patient had symptoms of valvular disease. This meta-analysis underscores that echocardiography is recommended in all patients with hyperprolactinemia who are candidate to be treated with or are under cabergoline therapy; monitoring cardiac valves is also recommended although precise follow- up for these patients will be likely provided by future longitudinal studies.

Topics: Aortic Valve; Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Hyperprolactinemia; Mental Disorders; Mitral Valve; Risk Factors; Tricuspid Valve

Valvular heart disease in patients being treated with ergot-derivative dopamine agonists (Ergot-DA) for Parkinson's disease has been reported to occur as a consequence of serotonine receptor stimulation. Goal of this analysis was to estimate the incidence of those changes from recently published studies and to determine its clinical relevance. Medline searches were performed to identify cross-sectional, echocardiographic studies comparing patients treated with dopamine agonists or controls, in terms of valvular changes. Observational studies of valve changes in Parkinsonian patients were used to estimate the incidence of severe valvulopathy. The results from 7 cross-sectional studies including 477 patients treated with Ergot-DA, 127 patients with non-Ergot-DA, and 364 control patients were analyzed. Moderate-to-severe valvular changes were detected in 26% of patients treated with Ergot-DA, 10% of patients treated with non-Ergot DA, and 10% of control patients. Severe valvulopathy was less than 1% both in cross-sectional and observational studies. The high rate of moderate valvular changes in patients treated with Ergot-DA suggests that close surveillance of the patients is required. Severe valvulopathy was less than 1% in the studies analyzed.

Topics: Antiparkinson Agents; Cabergoline; Cross-Sectional Studies; Dopamine Agonists; Drug Combinations; Echocardiography; Ergolines; Ergot Alkaloids; Heart Valve Diseases; Humans; Parkinson Disease; Pergolide; Product Surveillance, Postmarketing

Retroperitoneal and pleuropulmonary fibrosis are well known but rare complications of the treatment of Parkinson's disease with ergolinic dopamine agonists; however, until now, these complications have not substantially affected the routine clinical use of these drugs. The occurrence of restrictive valvular heart disease during treatment with pergolide and cabergoline caused concern about the safety of dopamine agonists in Parkinson's disease. Specifically, there is uncertainty whether fibrotic cardiac valvulopathy is due to exposure to these two ergolinic dopamine agonists or whether the abnormality is reversible. Changes in the heart valves can incur additional disability and worsen the clinical disorders of Parkinson's disease.. Population studies of patients with Parkinson's disease compared with non-parkinsonian controls have reported that pergolide and cabergoline have a similar risk of inducing fibrotic changes in cardiac valve leaflets. The fibrotic changes cause thickening, retraction, and stiffening of valves, which result in incomplete leaflet coaptation and clinically significant regurgitation, and have necessitated surgical valve replacement in some patients. Pergolide and cabergoline have high affinity for the 5-HT(2B) serotonin receptors, which are expressed in heart valves and might mediate mitogenesis and, in turn, the proliferation of fibroblasts. When analysed together, current population studies of similar designs and doses report 102 patients on cabergoline, 245 patients on pergolide, 181 patients on non-ergot agonists (pramipexole and ropinirole), and 177 non-parkinsonian controls. The frequency of moderate-to-severe regurgitation in at least one heart valve was higher in patients receiving cabergoline or pergolide than in patients taking non-ergot agonists or controls, and the incidence of new-onset valvulopathy was high in patients taking the ergot-derived drugs. WHERE NEXT?: Because of the routine prescription of pergolide and cabergoline, the switching of patients to different treatment regimens might be difficult. Moreover, whether the fibrotic changes are reversible is unknown. Finally, these adverse events do not occur in all patients, and no susceptibility factors are known. Prospective studies will assess the full effect of these abnormalities and help establish whether and when mitral valve tenting area abnormalities become clinically relevant during chronic treatment. The exact pathway leading to valvulopathy is unknown, although agonism of 5-HT(2B) receptors in the heart is implicated as a mediator in the process. Other ergolinic dopamine agonists, such as lisuride, and non-ergot dopamine agonists are devoid of 5-HT(2B) agonistic activity; therefore, their use might not induce fibrotic changes in heart valves. However, further prospective studies are needed. Such studies should also clarify the clinical relevance of mild-to-moderate echocardiographic changes and their natural history. Because of the clinical consequences of the adverse reactions, we suggest that affinity for 5-HT(2B) receptors is routinely tested in future drugs, in the laboratory or in animals, before they are given to patients.

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

Dopamine agonists (DAs), which can be categorized as ergot derived and non-ergot derived, are used in the treatment of Parkinson's disease.. This review describes the pharmacologic and pharmacokinetic properties of selected DAs and relates these characteristics to clinical outcomes, with an emphasis on adverse events.. Relevant articles were identified through a search of MEDLINE (to May 2006) using the terms dopamine agonists (or each individual drug name) and pbarmacokinetics, metabolism, drug-drug interaction, interactions, CYP450, fibrosis, valvular heart disease, tremor, clinical trials, reviews, and meta-analyses. Abstracts from recent sessions of the International Congress of Parkinson's Disease and Movement Disorders were also examined. Clinical studies with <20 patients overall or <10 patients per treatment group in the final analysis were excluded. All DAs that were graded at least possibly useful with respect to at least 3 of 4 items connected to the treatment/prevention of motor symptoms/complications in the most recent evidence-based medical review update were included. This resulted in a focus on the ergot-derived DAs bromocriptine, cabergoline, and pergolide, and the non-ergot-derived DAs pramipexole and ropinirole.. Bromocriptine, cabergoline, pergolide, and ropinirole, but not pramipexole, have the potential for drug-drug interactions mediated by the cytochrome P450 (CYP) enzyme system. The occurrence of dyskinesia may be linked to stimulation of the dopamine D(1) receptor, for which cabergoline and pergolide have a similar and relatively high affinity; bromocriptine, pramipexole, and ropinirole have been associated with a lower risk of dyskinesias. The valvular heart disease (VHD) and pulmonary and retroperitoneal fibrosis seen with long-term use appear to represent a class effect of the ergot-derived DAs that may be related to stimulation of serotonin 5-HT(2B) (and possibly 5-HT(2A)) receptors. The incidence of valvular regurgitation was 31% to 47% with ergot-derived DAs, 10% with non-ergot-derived DAs, and 13% with controls.. As reflected in the results of the clinical trials included in this review, dyskinesia associated with DA therapy may be linked to stimulation of the D(1) receptor. Fibrosis (including VHD) seemed to be a class effect of the ergot-derived DAs. Each of the DAs except pramipexole has the potential to interact with other drugs via the CYP enzyme system.

Topics: Animals; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Interactions; Dyskinesia, Drug-Induced; Ergolines; Heart Valve Diseases; Humans; Indoles; Pergolide; Pulmonary Fibrosis; Receptors, Dopamine

Cabergoline (CAB) has been found to be associated with increased risk of cardiac valve regurgitation in Parkinson's disease, whereas several retrospective analyses failed to detect a similar relation in hyperprolactinemic patients. The current study aimed at investigating cardiac valve disease before and after 24 and 60 months of continuous treatment with CAB only in patients with hyperprolactinemia.. Forty patients (11 men and 29 women, aged 38.7 ± 12.5 years) newly diagnosed with hyperprolactinemia entered the study. Cumulative CAB dose ranged from 12 to 588 mg (median 48 mg) at 24 months and 48-1260 mg (median 149 mg) at 60 months. All patients underwent a complete trans-thoracic echocardiographic examination. Valve regurgitation was assessed according to the American Society of Echocardiography.. At baseline, the prevalence of trace mitral, aortic, pulmonic, and tricuspid regurgitations was 20, 2.5, 10, and 40% respectively, with no patient showing clinically relevant valvulopathy. After 24 months, no change in the prevalence of trace mitral (P=0.78) and pulmonic (P=0.89) regurgitations and of mild aortic (P=0.89) and tricuspid (P=0.89) regurgitations was found when compared with baseline. After 60 months, the prevalence of trace tricuspid regurgitation was only slightly increased when compared with that after 24 months (37.5%; P=0.82), but none of the patients developed significant valvulopathy. No correlation was found between cumulative dose and prevalence or grade of valve regurgitation at both evaluations. Prolactin levels normalized in all patients but one.. CAB does not increase the risk of significant cardiac valve regurgitation in prolactinomas after the first 5 years of treatment.

Topics: Adult; Antineoplastic Agents; Cabergoline; Cohort Studies; Dopamine Agonists; Drug Monitoring; Early Diagnosis; Ergolines; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valves; Humans; Italy; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactinoma; Severity of Illness Index; Time Factors; Ultrasonography

Chronic low-dose cabergoline treatment for microprolactinoma may cause cardiac valve pathology, but the evidence is contradictory. We investigated whether the expectation of the echocardiographer could influence the report.. Transthoracic echocardiograms from 40 patients aged 49·3 ± 9·6 (mean ± SD) years (Men:Women 7:33) on long-term cabergoline and bromocriptine therapy (duration 9·94 ± 4·5 years) were randomly assigned to two groups of echocardiographers so that each echocardiogram was reported twice. One group was told that 'the patients were control subjects' (Group A) and the other that 'the patients were on dopamine agonist therapy which is known to cause valve disease' (Group B). An observer who was blind to the group scored the reports for regurgitation at each valve (scores 0-4; max 16 per case).. Mean total regurgitation score was significantly higher in Group B (1·43 ± 1·28; P = 0·014) than in Group A (0·73 ± 1·30). The difference was mainly from reporting trivial regurgitation: (mitral 16 vs 5, P = 0·005; tricuspid 17 vs 6, P = 0·007 and pulmonary 8 vs 1, P = 0·013). Mild regurgitation was uncommon (mitral 1 vs 1 and tricuspid 3 vs 6). Moderate regurgitation occurred in only one case and was associated with restriction of the leaflets consistent with the effects of cabergoline. Valve thickening was not reported in Group A, but in 9 (23%) mitral and 4 (10%) aortic valves in Group B.. Long-term, low-dose dopamine agonist therapy rarely causes cardiac valve disease, but operator bias can lead to over-reporting of both valve thickening and trivial regurgitation.

Topics: Adult; Antineoplastic Agents; Artifacts; Bias; Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Pituitary Neoplasms; Prolactinoma; Tricuspid Valve Insufficiency

Ergot-derived dopamine receptor agonists, especially pergolide and cabergoline, have been associated with an increased risk of valvular heart disease in patients treated for Parkinson's disease. Cabergoline at lower doses than those employed in Parkinson's disease is widely used in patients with prolactinomas, because of its high efficacy and tolerability; however, its safety with regard to cardiac valve disease is unknown. In order to assess the prevalence of cardiac valve regurgitation in patients with prolactinomas treated with long-term cabergoline, we performed a prospective and multicentric study including four university centers in the province of Quebec. A transthoracic echocardiogram was performed in 70 patients with prolactinomas treated with cabergoline for at least 1 year (duration of treatment, 55 +/- 22 months; cumulative dose 282 +/- 271 mg, mean +/- SD) and 70 control subjects matched for age and sex. Valvular regurgitation was graded according to the American Society of Echocardiography recommendations as mild, moderate, or severe. Moderate valvular regurgitation was found in four patients (5.7%) and five control subjects (7.1%) (P = 0.73). No patient had severe valvular regurgitation. There was no correlation between the presence of significant heart-valve regurgitation and cabergoline cumulative dose, duration of cabergoline treatment, prior use of bromocriptine, age, adenoma size, or prolactin levels. Our results show that low doses of cabergoline seem to be a safe treatment of hyperprolactinemic patients. However, in patients with prolonged cabergoline treatment, we suggest that echocardiographic surveillance may be warranted.

Topics: Adult; Cabergoline; Case-Control Studies; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Prolactinoma

To elucidate the association between treatment with ergot-derived dopamine agonists (EDDA) and valvular abnormalities amongst patients with idiopathic Parkinson's disease (IPD) and secondly, to analyse the yield of clinical screening for valvular heart disease.. A cross-sectional controlled study.. The cohort of IPD patients treated in the outpatient clinic, Department of Neurology, Aarhus University Hospital, Denmark.. A total of 138 IPD patients [median age 64 (39-87) years, 62% men] treated with either EDDA (n = 85) or non-EDDA (n = 53) for at least 6 months. Interventions. Patients were screened for valvular heart disease by clinical means and by examiner-blinded echocardiography. Main outcome measure was valvular regurgitation revealed by echocardiography.. Severe aortic regurgitation (n = 4) or moderate aortic (n = 12), mitral (n = 3) or tricuspidal valve regurgitation (n = 5) was found in 22 EDDA patients (25.9%). Two patients had coexistent moderate mitral and tricuspid valvular regurgitation. Two non-EDDA patients had moderate valve insufficiency (3.8%, P < 0.05). The adjusted relative risk for at least moderate valve insufficiency in the EDDA patients was 7.2% (P < 0.05). The sensitivity of detecting at least moderate valvular disease by cardiac murmur, dyspnoea, or the heart failure marker NT-proBNP (natriuretic peptide) was 62% for the neurologists and 93% for the cardiologist but with equally low specificity (30-35%).. EDDA was associated with a clinically important and statistically significant risk of at least moderate valve regurgitation. Clinical screening for valve disease was inadequate and it seems advisable to offer EDDA patients control with echocardiography.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care Facilities; Cabergoline; Cross-Sectional Studies; Denmark; Dopamine Agonists; Electrocardiography; Ergolines; Ergot Alkaloids; Female; Heart Valve Diseases; Humans; Logistic Models; Male; Middle Aged; Parkinson Disease; Severity of Illness Index; Ultrasonography

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

A 60-year-old patient, professor of physics, presented in 1999 with sudden-onset vitiligo associated with hyperprolactinemia and a prolactinoma. Fearful of potential surgical complications at the peak of his career, the patient declined surgery and opted for medical management with bromocriptine. The decreasing effectiveness of bromocriptine after 5 years required a switch to cabergoline. After a 15-year-course of cabergoline therapy with a cumulative dose of 572 mg, echocardiographic monitoring demonstrated aortic and mitral valve thickening and regurgitation. An additional 3 years of cabergoline treatment (cumulative dose: 649 mg) resulted in worsening valve thickening and regurgitation. It is well-recognized that such valvular changes may occur with high-dose cabergoline treatment. We report a case of mitral and aortic vavulopathy in a patient who was treated with long-term (18 years) low-dosage (.5-1 mg weekly) cabergoline. cabergoline, echocardiography, valvulopathy.

Topics: Bromocriptine; Cabergoline; Ergolines; Heart Valve Diseases; Humans; Middle Aged; Pituitary Neoplasms

Topics: Cabergoline; Ergolines; Heart Valve Diseases; Humans; Hyperprolactinemia; Prevalence

Topics: Cabergoline; Ergolines; Heart Valve Diseases; Humans; Hyperprolactinemia; Prevalence

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.

Topics: Adult; Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Heart Valves; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Prospective Studies; Treatment Outcome; Young Adult

Uncertainty exists whether the long-term use of ergot-derived dopamine agonist (DA) drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease and whether current regulatory authority guidelines for echocardiographic screening are clinically appropriate.. Our objective was to provide follow-up echocardiographic data on a previously described cohort of patients treated with DA for lactotrope pituitary tumors and to explore possible associations between structural and functional valve abnormalities with the cumulative dose of drug used.. Follow-up echocardiographic data were collected from a proportion of our previously reported cohort of patients; all had received continuous DA therapy for at least 2 years in the intervening period. Studies were performed according to British Society of Echocardiography minimum standards for adult transthoracic echocardiography. Generalized estimating equations with backward selection were used to determine odds ratios of valvular heart abnormalities according to tertiles of cumulative cabergoline dose, using the lowest tertile as the reference group.. Thirteen centers of secondary/tertiary endocrine care across the United Kingdom were included.. There were 192 patients (81 males; median age, 51 years; interquartile range [IQR], 42-62). Median (IQR) cumulative cabergoline doses at the first and second echocardiograms were 97 mg (20-377) and 232 mg (91-551), respectively. Median (IQR) duration of uninterrupted cabergoline therapy between echocardiograms was 34 months (24-42). No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality.. 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.

Topics: Adult; Aged; Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Female; Follow-Up Studies; Heart Valve Diseases; Humans; Hyperprolactinemia; Male; Middle Aged; Prevalence; United Kingdom

On June 2008, the European Medicines Agency (EMA) introduced changes to the Summary of Product Characteristics (SPC) for cabergoline and pergolide, to reduce the risk of cardiac valvulopathy in users of these drugs. To assess the effectiveness of EMA recommendations in Italian clinical practice, we retrospectively reviewed medical charts of patients with degenerative Parkinsonism treated with cabergoline in three large Italian clinics between January 2006 and June 2012. The prevalence and the severity of cardiac valve regurgitation were assessed in patients who stopped cabergoline therapy prior to June 2008 or continued therapy after that date. In addition, the proportion of patients undergoing echocardiographic examination in each cohort was evaluated. A total of 61 patients were available for evaluation. The proportion of patients who underwent a baseline echocardiographic examination increased from 64 % in the period before the 2008 SPC changes to 71 % among those who continued treatment after that date. However, only 18 and 29 % of patients underwent at least two echocardiographic examinations during the pre-SPC and cross-SPC change period, respectively. No severe cardiac valve regurgitation was documented in any of the study patients using cabergoline either prior or after 26th June 2008. Our findings show that the 2008 changes to the SPC resulted in an increase in physicians' awareness of cabergoline-induced valvulopathy risk in Italy. However, only a small percentage of patients underwent serial echocardiography. Further efforts are needed to achieve better compliance with the prescribing guidelines for cabergoline treated patients in clinical practice.

Topics: Aged; Antiparkinson Agents; Cabergoline; Cohort Studies; Echocardiography; Ergolines; Female; Guideline Adherence; Heart Valve Diseases; Heart Valves; Humans; Incidence; Italy; Male; Middle Aged; Parkinson Disease; Pergolide; Practice Guidelines as Topic; Prevalence; Retrospective Studies; Risk Factors; Supranuclear Palsy, Progressive

Concern exists in the literature that the long-term use of ergot-derived dopamine agonist drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease.. The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking dopamine agonists as treatment for lactotrope pituitary tumors and to explore any associations with the cumulative dose of drug used.. A cross-sectional echocardiographic study was performed in a large group of patients who were receiving dopamine agonist therapy for hyperprolactinemia. Studies were performed in accordance with the British Society of Echocardiography minimum dataset for a standard adult transthoracic echocardiogram. Poisson regression was used to calculate relative risks according to quartiles of dopamine agonist cumulative dose using the lowest cumulative dose quartile as the reference group.. Twenty-eight centers of secondary/tertiary endocrine care across the United Kingdom participated in the study.. Data from 747 patients (251 males; median age, 42 y; interquartile range [IQR], 34-52 y) were collected. A total of 601 patients had taken cabergoline alone; 36 had been treated with bromocriptine alone; and 110 had received both drugs at some stage. The median cumulative dose for cabergoline was 152 mg (IQR, 50-348 mg), and for bromocriptine it was 7815 mg (IQR, 1764-20 477 mg). A total of 28 cases of moderate valvular stenosis or regurgitation were observed in 24 (3.2%) patients. No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality.. 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.

Topics: Adult; Cabergoline; Cross-Sectional Studies; Dopamine Agonists; Echocardiography; Ergolines; Ergot Alkaloids; Female; Heart Valve Diseases; Humans; Hyperprolactinemia; Male; Middle Aged; Prevalence; United Kingdom

In this study, we aimed to evaluate the impact of cabergoline use in patients with Parkinson's disease on valvular and biventricular functions.. In this observational cohort study, patients with Parkinson disease were divided into 2 groups as 34 patients (41.2% female, age; 57.4±15.3 years) using cabergoline (Group 1) and 42 patients (61.9% female, age; 53.7±7.1 years) not using cabergoline (Group 2). In addition to conventional echocardiography and diastolic functions, tissue Doppler imaging was used to evaluate both global and regional systolic - diastolic functions. Correlations were assessed using Pearson correlation coefficient for normally distributed variables.. In group 1 patients cabergoline was used for 7.7±5.1 years and mean and cumulative cabergoline dose were 3.3±1.1 mg and 9.8±7.0 g respectively. Left ventricular systolic functions and tissue Doppler measurements of septal and lateral mitral annulus and right ventricular systolic and diastolic velocities were similar between groups. Mitral valve tenting area was significantly higher in patients using cabergoline (p=0.007). The association between cumulative cabergoline dose and diastolic functions was also evaluated which revealed that among diastolic function parameters, Epeak (r=0.253, p=0.042), E/A (r=0.256, p=0.026) and DT (r=-0.382, p=0.001) were correlated with cumulative cabergoline dose. There was a positive correlation between cumulative cabergoline dose and duration of cabergoline therapy with composite regurgitation score (r=0.435, p<0.001; r=0.485, p<0.001, respectively).. Our findings indicated that despite the well known effects of cabergoline on valvular functions, we did not observe any alteration in systolic functions, but diastolic functions which was associated with cumulative cabergoline dose in patients with Parkinson's disease.

Topics: Cabergoline; Cohort Studies; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Parkinson Disease

To review the current literature regarding dopamine agonists (DAs) and the risk of the development of cardiac valve disease.. PubMed searches were performed to identify all of the available published data on DAs and valve disease in patients with hyperprolactinemia.. Most of the available echocardiographic data from patients treated for hyperprolactinemia are from case-control studies, and prospective data are limited. The majority of the studies do not support an increased risk of clinically significant valve disease in hyperprolactinemic patients treated with cabergoline. Evidence for the use of echocardiography is needed to limit unnecessary procedures and healthcare costs. Based on the published literature describing Parkinson's disease (PD) patients, the daily and cumulative doses of cabergoline are important factors. Considerations to minimize exposure to cabergoline, such as surgical resection of adenomas or medication withdrawal in responders, may be appropriate depending on the clinical setting.. There is no conclusive evidence that cabergoline causes clinically significant cardiac valve disease at the usual doses for the treatment of hyperprolactinemia. Although current recommendations from regulatory agencies advise routine echocardiography for patients receiving cabergoline, evidence-based criteria would be useful both to identify patients at risk and generate appropriate screening protocols.

Topics: Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Hyperprolactinemia; Risk

Topics: Adult; Cabergoline; Ergolines; Female; Heart Valve Diseases; Humans; Hyperprolactinemia; Male; Middle Aged

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.

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Prolactinoma

Topics: Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Cabergoline; Cohort Studies; Cross-Sectional Studies; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Odds Ratio; Parkinson Disease; Retrospective Studies; Risk Assessment

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

Prolactinoma is the most common pituitary adenoma, and dopamine agonists( BRC, and CAB) is the primary therapy. Recently, the increased prevalance of cardiac valvular disease in patients treated with DAs for Parkinson's disease has raised concerns about the safety of this drug in patients with prolactinoma. CAB and pergolide are frequently reported to cause valvulopathy, there are very few studies showing this side effect in BRC administiration which has less potent agonism of 5-HT2B receptors. Male patients who are known to have higher prevalance of macroadenomas compared to women. The dosage of DAs administered were rarely evaluated.. We performed a retrospective chart to evaluate the medical management and treatment outcomes of male patients with macro/giant prolactinomas. We evaluated 22 patients with prolactinoma managed with DAs therapy alone for at least 1 year. All patients were followed for a mean of 61 months. Pretreatment echocardiographic examination were not available at that time.. None of them had any resistance or intolerance to DAs. The mean tumor shrinkage was 62%. In three patients the macroprolactinoma disappeared, in two patients the tumor shrinkage was 93% and 70%. The DAs therapy was discontinued in these patient. After a follow up neither MRI showed a recurrence or enlargement of the adenoma, nor prolactin levels showed any elevation. The echocardiography were performed at the last visit of each patient and no valvulopathy in any of the patients on DAs therapy were detected.. DAs are effective, and safe for valve morphology with mean cumulative doses of 155 mg CAB, and 7 301 mg BRC in patients with macroprolactinoma.

Topics: Adult; Aged; Bromocriptine; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactinoma; Retrospective Studies; Risk Factors; Ultrasonography; Young Adult

The effects of cabergoline on cardiac valves have been extensively studied in Parkinson's disease and hyperprolactinemia but not in acromegaly, a condition at risk of cardiac valve abnormalities.. We examined the prevalence and incidence of heart valve disease and regurgitation in a series of patients with acromegaly treated with cabergoline, by comparison with matched patients who had never received this drug.. We conducted a cross-sectional and longitudinal study in a single referral center.. Forty-two patients who had received cabergoline at a median cumulative dose of 203 mg for a median of 35 months were compared to 46 patients with acromegaly who had never received cabergoline and who were matched for age, sex, and disease duration. A subgroup of patients receiving cabergoline (n = 26) was evaluated longitudinally before and during cabergoline treatment and compared to a group not receiving cabergoline and followed during the same period (n = 26). Two-dimensional and Doppler echocardiographic findings were reviewed by two cardiologists blinded to treatment.. Demographic and clinical features were not significantly different between the groups. Compared to acromegalic controls, patients receiving cabergoline did not have a higher prevalence or incidence of valve abnormalities. A slightly higher prevalence of aortic valve regurgitation and remodeling was found in the controls relative to the cabergoline-treated patients (P < 0.02 and P < 0.03, respectively), but this was related to the presence of aortic dilatation.. Cabergoline therapy is not associated with an increased risk of cardiac valve regurgitation or remodeling in acromegalic patients at the doses used in this study.

Topics: Acromegaly; Adolescent; Adult; Aged; Aortic Valve Insufficiency; Cabergoline; Cross-Sectional Studies; Dopamine Agonists; Echocardiography; Echocardiography, Doppler; Ergolines; Female; Heart Valve Diseases; Heart Valves; Humans; Hypertrophy, Left Ventricular; Longitudinal Studies; Male; Middle Aged; Mitral Valve Insufficiency; Retrospective Studies; Tricuspid Valve Insufficiency; Young Adult

In a previous echocardiographic prevalence study we reported a significant increase in the frequency of heart valve regurgitation in patients with Parkinson's disease taking the ergot-derived dopamine agonists pergolide and cabergoline versus controls. We followed-up our original cohort of patients to ascertain whether valvulopathy regressed after discontinuation of treatment and/or its incidence increased over time.. Prospective follow-up of 101 patients treated with ergot-derived dopamine agonists included in the prevalence study: 53 given pergolide and 48 cabergoline (64% male; 66.4 ± 8.7 years of age, 11.5 ± 5.9 years of disease, 21.8 ± 5.9 months of follow-up); 55 stopped treatment while 46 continued. The main outcomes measures, were: echocardiographic quantification of regurgitant valve disease, abnormal leaflet, or cusp thickening and measurement of mitral valve tenting area.. Valve abnormalities regressed in about one third of patients with significant multivalvular and in about half of the patients with monovalvular regurgitation who withdrew; no progression was observed in remaining patients. Patients continuing ergot-derived dopamine agonists showed progression of cardiac valvulopathy: seven new cases with three to four regurgitation grade of any valve occurred during follow-up; this regarded also patients who had been on pergolide for many years.. Owing to the persistence of risk of heart valve damage over time and the lack of its mid-term reversibility in many patients, we believe that pergolide and cabergoline should be prescribed only when therapeutic alternatives with a better risk/benefit ratio are unavailable and the patient has access to echocardiography.

Topics: Adult; Aged; Antiparkinson Agents; Cabergoline; Dopamine Agonists; Ergolines; Female; Follow-Up Studies; Heart Valve Diseases; Humans; Italy; Male; Middle Aged; Parkinson Disease; Patient Selection; Pergolide; Prevalence; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Ultrasonography

Use of the ergot-derived dopamine receptor agonists (cabergoline and pergolide) is associated with an increased risk of cardiac valvulopathy. Pergolide was withdrawn from the US market in 2007 because of the risk of valvular heart disease, while the European Medicines Agency (EMA) required a reduction in the maximum daily dosage of cabergoline and pergolide from 6 mg/day to 3 mg/day in 2008. In Japan, the package inserts of both drugs were revised in April 2007 to request that physicians conduct periodic ultrasonic cardiography (UCG) examinations for patients taking cabergoline or pergolide. Also, through face-to-face communication with medical representatives of drug companies, physicians were informed that use of cabergoline and pergolide has increased the risk of valvulopathy. However, cabergoline and pergolide have remained in wide use, even following the regulatory actions.. The objective of this study was to assess the impact of actions, including the package insert revision in April 2007, to encourage periodic UCG.. Data on monthly claims (January 2005-October 2008) covering 330 000 patients were obtained from a Japanese database vendor. We selected patients ≥40 years of age with Parkinson's disease. The impact of the regulatory action on the proportion of patients with Parkinson's disease prescribed cabergoline or pergolide was assessed by segmented regression analysis and by a statistical model of the rates of UCG examination in patients taking/not taking cabergoline or pergolide before and after the action. We also compared the use of cabergoline and pergolide before and after the action with that of other antiparkinson drugs.. Of 574 patients with Parkinson's disease, the proportion of patients prescribed cabergoline or pergolide did not decrease but rather tended to increase after the action when analysed by segmented regression analysis (p = 0.13). Similarly, the proportion of the prevalent and incident users of cabergoline or pergolide did not change between two 19-month periods before and after the action. The adjusted rates of UCG examination per person-year before and after the action were both 0.02 in those not prescribed cabergoline or pergolide, but 0.02 before the action and 0.09 after the action in those taking either drug. The excess UCG examination rate of cabergoline or pergolide attributable to the action was 0.08 per person-year (95% CI 0.03, 0.11). While 1 of 49 (2%) patients taking cabergoline or pergolide had a UCG up to 19 months before the action, 9 of 36 (25%) patients taking cabergoline or pergolide had a UCG up to 19 months after the action. Annual sales from 2004 to 2008 were 195, 195, 170, 110 and 75 billion yen, respectively, and the number of valvulopathy events, including incompetence of aortic/mitral/tricuspid valves and cardiac valve disease, per annual sales from 2004 to 2008 were estimated at 0.23, 0.03, 0.08, 0.25 and 0.19 per billion yen, respectively.. Following the actions in April 2007, no decrease in the use of cabergoline or pergolide occurred, although more patients administered the drug underwent a UCG. However, those undergoing a UCG represented one-quarter of the total number prescribed cabergoline or pergolide. To mitigate the risk, additional risk management tools such as patient registration may be needed to secure careful clinical examination (including UCG examination, if necessary) for cardiac function.

Topics: Cabergoline; Databases, Factual; Dopamine Agonists; Drug Prescriptions; Drug Utilization Review; Ergolines; Government Regulation; Heart Valve Diseases; Humans; Insurance Claim Review; Japan; Legislation, Drug; Parkinson Disease; Pergolide; Regression Analysis; Ultrasonography

The ergot-derived dopamine agonists, cabergoline and pergolide, are associated with valvulopathy risk. In Japan, product labels were revised in April 2007 to recommend periodic echocardiography for patients taking these dopamine agonists, however, the compliance of physicians to follow through with this recommendation is unknown. This study assessed changes in echocardiography evaluation of patients with Parkinson's disease (PD) taking cabergoline or pergolide before and after the label revision and examined the factors related with echocardiography performance.. Medical claim data from January 2005 to December 2008 were used. Patients were divided into a C-P group (prescribed either cabergoline or pergolide) or reference group (prescribed other anti-PD drugs), and further classified based on whether they were prescribed these drugs "pre-revision" or "post-revision." The Cochran-Armitage trend test was used to compare the proportion of echocardiograms obtained amongst these groups before and after the revision. The frequencies of echocardiograms performed among the treatment groups for each period were compared by Fisher's exact test.. A total of 222 subjects (C-P, 73; reference, 149) were assessed. The proportion of C-P patients undergoing echocardiography increased from 4.8% to 27.9% after revision of product labels (p=0.001), which was higher than those in the reference group following label revisions (11.0%) (p=0.014). Prescription duration of C-P after the revision was longer in the patients with echocardiography than without echocardiography (p=0.026).. Although echocardiography evaluations increased, more than 70% of PD patients prescribed cabergoline or pergolide did not undergo such assessment despite the product label recommendation. Adherence to drug safety recommendations should be facilitated with more feasible and effective measures.

Topics: Adult; Aged; Cabergoline; Dopamine Agonists; Drug Labeling; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Incidence; Japan; Male; Middle Aged; Parkinson Disease; Pergolide; Retrospective Studies; Risk Factors

Fibrotic valvular heart disease (VHD) has been observed in patients with Parkinson's disease treated with dopamine receptor agonists such as pergolide and cabergoline. 5-Hydroxytryptamine(2B) receptor (5-HT(2B)R) agonism is the most likely cause, but other 5-HT receptors may also play a role in VHD. We aimed at characterizing the molecular fragment of cabergoline responsible for agonism at 5-HT(2B)R and 5-HT(2A)R. Cabergoline with an allyl substituent at N(6) behaved as a potent 5-HT(2B)R full agonist in relaxation of porcine pulmonary arteries and as a weaker 5-HT(2A)R partial agonist in contraction of coronary arteries. The same was true for cabergoline derivatives with cyclopropylmethyl, propyl, or ethyl at N(6). However, agonism was converted into antagonism, when the N(6) substituent was methyl. 6-Methylcabergoline retained agonism compared with cabergoline at human dopamine D(2LONG) and human dopamine D(2SHORT) receptors as determined by guanosine 5'-O-(3-[(35)S]thio)triphosphate binding. In porcine aortic valve cusps, 5-HT-induced contractions were inhibited by ketanserin (5-HT(2A/2C)R antagonist) but not by N-(1-methyl-1H-5-indolyl)-N'-(3-methyl-5-isothiazolyl)urea (SB204741) (5-HT(2B)R antagonist). In porcine valvular interstitial cells, cabergoline-induced activation of extracellular signal-regulated kinase (ERK) 1/2, an initiator of cellular proliferation and activity, was blocked by (R)-(+)-4-(1-hydroxy-1-(2,3-dimethoxyphenyl)methy1)-N-2-(4-fluorophenylethyl)piperidine (MDL100907) (5-HT(2A)R antagonist) and N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1,1'-biphenyl-4-carboxamide (GR127935) (5-HT(1B)R antagonist), whereas the stimulatory effect on [(3)H]proline and [(3)H]glucosamine incorporations (indices of extracellular matrix collagen and glycosaminoglycan) was blocked by MDL100907. We conclude that the bulky N(6) substituent of cabergoline is responsible for 5-HT(2A)R and 5-HT(2B)R agonism. The increased ERK1/2 phosphorylation and production of extracellular matrix by cabergoline are mediated by 5-HT(2A)Rs. However, the moderate potency of cabergoline at native 5-HT(2A)Rs suggests that these are not the preferential target in VHD in vivo.

Topics: Animals; Cabergoline; Cells, Cultured; CHO Cells; Cricetinae; Cricetulus; Ergolines; Heart Valve Diseases; Humans; Pulmonary Artery; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2B; Serotonin Receptor Agonists; Swine

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

Topics: Antineoplastic Agents; Antiparkinson Agents; Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans

Dopamine agonists (DAs) are the first-line therapy for the treatment of hyperprolactinemia, with cabergoline, an ergot-derived selective D(2)-receptor agonist, being the preferred and most widely used drug. Recent studies reported cardiac valve regurgitations in patients with Parkinson's disease treated with high doses of DA, raising concerns about the safety of cabergoline in patients with hyperprolactinemia. To date, seven case-control studies have examined the potential association between cardiac valvular abnormalities and cabergoline therapy in patients with hyperprolactinemia. Overall, a total of 463 patients exposed to low doses of cabergoline (mean cumulative doses: 204-443 mg) for a mean duration of 45-79 months have been included in these studies. Patients in all the studies were asymptomatic without clinical signs of cardiac disease. Six studies did not show any association between cabergoline therapy and clinically relevant valvular regurgitation, whereas one study found an increased rate of moderate tricuspid regurgitation. In this report, we review and discuss the results of these studies and emphasize the limitations of the methodology used in the published literature. The clinical significance of the present findings has yet to be confirmed by future larger prospective studies with rigorous echocardiographic protocols and prolonged duration of follow-up.

Topics: Adult; Cabergoline; Case-Control Studies; Clinical Trials as Topic; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Receptors, Dopamine D2

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

Cabergoline is a highly effective medical treatment for patients with hyperprolactinaemia. There is an increased risk of valvular heart disease in patients receiving cabergoline for Parkinson's disease. This study examined whether cabergoline treatment of hyperprolactinaemia is associated with a greater prevalence of valvulopathy.. Cross-sectional, two-dimensional echocardiographic study performed by a single echocardiographer.. Seventy-two patients (median age 36 years, 19 men) receiving cabergoline for hyperprolactinaemia, and 72 controls prospectively matched for age, sex and cardiovascular risk factors. Measurements Assessment of valvular mobility, regurgitation and morphology.. Median cumulative dose exposure for cabergoline was 126 (58-258) mg, and patients had received cabergoline for 53 (26-96) months. The frequency of mild mitral regurgitation was identical (5/72, 7%) in patient and control groups. Mild aortic regurgitation was not significantly different between groups (4/72 [controls] vs 2/72 [patients], P = 0.681). There was only one case of tricuspid regurgitation, which was mild and observed in a cabergoline-treated patient. Nodular thickening of the right coronary cusp, noncoronary cusp or left coronary cusp of the aortic valve was observed at a similar frequency in both groups. There were no cases of extensive thickening of any valvular leaflet.. Our data demonstrates that there is no association between cabergoline treatment for hyperprolactinaemia and valvulopathy. This study therefore supports continued use of low-dose cabergoline for patients with hyperprolactinaemia.

Topics: Adult; Antiparkinson Agents; Blood Pressure; Cabergoline; Cross-Sectional Studies; Dose-Response Relationship, Drug; Echocardiography; Ergolines; Female; Heart Valve Diseases; Heart Valves; Humans; Hyperprolactinemia; Male; Middle Aged; Prospective Studies; Risk Assessment; Ventricular Function, Left; Ventricular Function, Right

An association between ergot-derived dopamine agonists and asymptomatic valvular heart disease in Parkinson's disease has been established. For safe use of these agonists, it is important to specify those at high risk for valvular heart disease among patients with Parkinson's disease. We performed a nested case-control study of 223 patients with Parkinson's disease. In results of multivariable logistic analyses, use of pergolide, use of cabergoline, age, male sex, and hypertension were independent significant risk factors for left-sided valvular regurgitation. In patients receiving cabergoline or pergolide, elderly (>or=70 years) hypertensive patients had a markedly high risk for valvular regurgitation (odds ratio 94.5) as compared to non-elderly (<70 years) patients without hypertension. The risk of valvular regurgitation caused by pergolide or cabergoline was found to be highly enhanced by comorbid hypertension or aging, suggesting that special attention should be paid when prescribing cabergoline or pergolide for those patients.

Topics: Age Factors; Aged; Benzothiazoles; Bromocriptine; Cabergoline; Case-Control Studies; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Hypertension; Male; Parkinson Disease; Pergolide; Pramipexole; Risk Factors

The use of high doses of the ergot-derived dopamine agonist cabergoline (> 3 mg/day), especially with cumulative doses > 4000 mg, has been associated with an increase in cardiac valvular thickening and significant (moderate to severe) regurgitation. Whether lower doses commonly used in the treatment of prolactinomas (0.25-3 mg/week) are also associated with significant valvulopathy is controversial. The mitral valve tenting area, a subclinical index of leaflet stiffening, has also been correlated with the cumulative dose of cabergoline and severity of valvular regurgitation.. We performed transthoracic echocardiography (TTE) on 50 prolactinoma patients (48% macroprolactinomas, 52% microprolactinomas, 30 male, 20 female, age 51.2 +/- 2.2 years, mean +/- SEM) who had been taking cabergoline for 6.6 +/- 0.5 years (range 1-13 years) with cumulative doses of 443 +/- 53 mg, to determine the prevalence of significant valvular thickening (> 0.5 cm) and regurgitation, and measured the mitral valve tenting area and height. The results were compared to those from age- and sex-matched controls with normal left ventricular function.. No significant valvular thickening or regurgitation of any valve was detected in the prolactinoma group and the prevalence of mild valvular regurgitation was not higher than in the case-control group. The mitral valve tenting area and height were not significantly greater than in the control group. There was no correlation between tenting area or height and cumulative cabergoline dose.. We found no evidence of increased mitral valve tenting area/height, valvular thickening or significant regurgitation with the long-term administration of the commonly used doses of cabergoline to treat prolactinoma.

Topics: Aortic Valve Insufficiency; Cabergoline; Calcinosis; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Prolactinoma; Ventricular Dysfunction, Left

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: Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Heart Valve Diseases; Heart Valves; Humans; Hyperprolactinemia; Parkinson Disease; Pergolide; Tricuspid Valve Insufficiency

Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Hyperprolactinemia

Topics: Antiparkinson Agents; Bromocriptine; Cabergoline; Case-Control Studies; Cross-Sectional Studies; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Hyperprolactinemia; Male; Parkinson Disease; Pergolide; Prolactin; Serotonin 5-HT2 Receptor Agonists; Ultrasonography

Treatment with ergot-derived dopamine agonists, pergolide, and cabergoline has been associated with an increased frequency of valvular heart disease in Parkinson's disease. The aim of the present study was to assess the prevalence of valvular heart disease in patients treated with dopamine agonists for prolactinomas.. This was a cross-sectional study.. We performed two-dimensional and Doppler echocardiography in 78 consecutive patients with prolactinoma (mean age 47 +/- 1.4 yr, 26% male, 31% macroprolactinoma) treated with dopamine agonists for at least 1 yr (mean 8 +/- 0.6 yr) and 78 control subjects. Patients were classified according to treatment: patients treated with cabergoline (group 1: n = 47) and patients not treated with cabergoline (group 2: n = 31).. Clinically relevant valvular heart disease was present in 12% of patients (nine of 78) vs. 17% of controls (13 of 78) (P = 0.141) and 17% (eight of 47) of patients treated with cabergoline vs. 3% (one of 31) of patients not treated with cabergoline (P = 0.062). Mild tricuspid regurgitation was present in 41% of patients vs. 26% of controls (P = 0.042), and aortic valve calcification was present in 40% of patients, compared with 18% of controls (P = 0.003). There was no relation between the cumulative dose of cabergoline and the presence of mild, moderate, or severe valve regurgitation.. Several years of dopamine agonist treatment in patients with prolactinomas is associated with increased prevalence of aortic valve calcification and mild tricuspid regurgitation but not with clinically relevant valvular heart disease. Therefore, additional studies on the adverse cardiac effects of dopaminergic drugs in prolactinoma are warranted, especially in patients with much longer use of these drugs.

Topics: Adult; Aortic Valve; Cabergoline; Calcinosis; Case-Control Studies; Cross-Sectional Studies; Disease Progression; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactinoma; Time Factors; Tricuspid Valve Insufficiency

Recent trials suggest that using ergot-derived dopamine agonists such as cabergoline in the treatment of Parkinson's disease is associated with an increased risk of valvular heart disease. However, the dose of cabergoline used to treat hyperprolactinaemia is considerably less than that used in Parkinson's disease.. A cross-sectional comparative assessment. Forty-four patients treated with cabergoline for hyperprolactinaemia underwent transthoracic echocardiography and were compared with 566 sequential subjects complaining of palpitations, taken from a contemporary echocardiography database.. The mean cumulative dose of cabergoline in the cases was 311 mg. There was no significant, severe or moderate, right- or left-sided valvular regurgitation in either group. Left heart: in the mitral and aortic valves, the rate of mild and trivial valvular regurgitation was not different between the two groups. Right heart: mild tricuspid and pulmonary regurgitation on colour Doppler alone was increased significantly in the cabergoline group, odds ratios of 3.1 and 7.8 respectively (95% confidence interval 1.0-9.6 and 0.8-78.4, P=0.04 and P<0.0001 respectively).. Cabergoline at doses sufficient to suppress hyperprolactinaemia for a period of 3-4 years is not associated with an increased risk of clinically significant valvular regurgitation.

Topics: Adult; Cabergoline; Cross-Sectional Studies; Databases, Factual; Dopamine Agonists; Echocardiography; Echocardiography, Doppler, Color; Ergolines; Female; Heart Valve Diseases; Humans; Hyperprolactinemia; Male; Middle Aged; Risk Factors

We experienced 2 patients of valvular heart disease in Parkinson's patients taking cabergoline. Patient 1 was a 79-year-old woman who began taking 4 mg cabergoline daily after being diagnosed with Parkinson's disease (PD) in June 2003. She presented with dyspnea in November 2005. The patient had cardiomegaly, pulmonary congestion, and pleural effusion, and an echocardiogram showed valvular heart disease in the form of aortic regurgitation (AR) (grade I), tricuspid regurgitation (TR) (grade I), and mitral regurgitation (MR) (grade III). Cabergoline was thought to have caused these phenomena, so it was replaced with pramipexole, and after administration of diuretics and angiotensin-converting enzyme inhibitors (ACEIs) the patient's symptoms gradually disappeared. MR, AR and TR also disappeared 3 months later. Patient 2 was a 74-year-old woman who presented with sluggish movement in April 2001 and subsequently developed Parkinson's. While being administered 700 mg levodopa (Menesit) and 4 mg cabergoline, the patient presented with shortness of breath in April 2005. An echocardiogram showed valvular heart disease in the form of MR (grade I) and TR (grade I). Heart function improved with the administration of diuretics. However, heart function again worsened in November 2005, and the patient presented with edema of the lungs and lower limbs. An echocardiogram in January 2006 showed worsening MR (grade III) and TR (grade II), and the patient also had pulmonary hypertension. ACEIs were administered along with diuretics and cabergoline was replaced with pramipexole, but the patient also developed malignant syndrome and disseminated intravascular coagulation (DIC) and later died. Patient 2 is the first case in Japan of death due to heart failure caused by the side effects of cabergoline. Caution is usually needed when treating a Parkinson's patient for valvular heart disease due to a dopamine agonist, and periodic checks for heart murmurs and echocardiography are crucial. When signs of heart failure develop during treatment with an ergot preparation of dopamine agonist, it is essential to immediately either stop the administration of the ergot preparation or change to a non-ergot preparation of dopamine agonist.

Topics: Aged; Antiparkinson Agents; Cabergoline; Ergolines; Fatal Outcome; Female; Heart Failure; Heart Valve Diseases; Humans; Parkinson Disease

To determine the prevalence of valvular heart disease in a cohort of patients taking cabergoline for the management of hyperprolactinemia.. A retrospective review of medical records identified patients with hyperprolactinemia who underwent evaluation at Vanderbilt University Medical Center between January and June 2007. The medical records of those patients who were prescribed cabergoline and who underwent elective echocardiography were reviewed for details pertaining to cardiac valvular abnormalities and cabergoline use.. Forty-five patients (mean age, 41 +/- 10 years [SD]) taking 0.91 +/- 0.96 mg of cabergoline per week for a mean duration of 39 +/- 29 months underwent echocardiography. Abnormalities of the cardiac valves were present in 3 patients (7%): 1 patient exhibited mild mitral regurgitation, 1 patient had focal aortic valve thickening, and 1 patient demonstrated mitral valve thickening. We found no significant difference in either the cumulative dose of cabergoline (P = .800) or the duration of cabergoline therapy (P = .745) between those patients with and those without these echocardiographic abnormalities.. We found echocardiographic valve abnormalities in 3 of 45 patients (7%) who had been prescribed cabergoline for the management of hyperprolactinemia. This prevalence of valvular heart disease after approximately 3 years of cabergoline treatment is no different from that previously reported in normal populations as determined by echocardiography.

Topics: Adult; Cabergoline; Cohort Studies; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Hyperprolactinemia; Male; Middle Aged

Topics: Adult; Cabergoline; Dopamine Agonists; Drug Resistance; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Receptors, Dopamine; Young Adult

The cardiac valvular risk associated with lower exposure to cabergoline in common endocrine conditions such as hyperprolactinemia is unknown.. We performed a cross-sectional, case-control echocardiographic study to assess the valvular status in 102 subjects receiving cabergoline for endocrine disorders and 51 matched control subjects. Cabergoline treatment ranged from 12 to 228 months, with a cumulative dose of 18-1718 mg. Valvular regurgitation was equally prevalent in both groups and was almost exclusively mild. Two cabergoline-treated subjects had moderate mitral regurgitation; there was no relationship between cabergoline dose and the presence or severity of mitral valve regurgitation (P=NS). Mitral valve tenting area was significantly greater in the cabergoline group when compared with the control subjects (P=0.03). Mitral valve leaflet thickening was observed in 5.9% of cabergoline-treated subjects; no relationship with the cumulative cabergoline dose was found. No patient had aortic or tricuspid valvular restriction.. No significantly increased risk of clinically relevant cardiac valve disorders was found in subjects treated with long-term cabergoline therapy at the doses used in endocrine practice. While exposure to cabergoline appears to be safe during low-dose long-term therapy, an association with subclinical changes in mitral valve geometry cannot be completely excluded.

Topics: Adult; Aged; Cabergoline; Cross-Sectional Studies; Dopamine Agonists; Echocardiography; Endocrine System Diseases; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Risk Factors

The case of a restrictive valve disease associated with cabergoline, an ergot alkaloid agonist used in the treatment of Parkinson's disease, is described. Cardiovascular and periodical follow-up assessment may be required when these drugs are prescribed.

Topics: Antiparkinson Agents; Cabergoline; Ergolines; Female; Heart Valve Diseases; Humans; Middle Aged; Mitral Valve Insufficiency

Topics: Antiparkinson Agents; Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Pergolide; Receptor, Serotonin, 5-HT2B; Serotonin 5-HT2 Receptor Agonists; Serotonin Receptor Agonists

Case reports and echocardiographic studies suggest that the ergot-derived dopamine agonists pergolide and cabergoline, used in the treatment of Parkinson's disease and the restless legs syndrome, may increase the risk of cardiac-valve regurgitation.. We used data from the United Kingdom General Practice Research Database to identify a population-based cohort comprising 11,417 subjects 40 to 80 years of age who were prescribed antiparkinsonian drugs between 1988 and 2005. We conducted a nested case-control analysis within this cohort in which each patient with newly diagnosed cardiac-valve regurgitation was matched with up to 25 control subjects from the cohort, according to age, sex, and year of entry into the cohort. Incidence-rate ratios for cardiac-valve regurgitation with the use of different dopamine agonists were estimated by conditional logistic-regression analysis.. Of 31 case patients with newly diagnosed cardiac-valve regurgitation, 6 were currently exposed to pergolide, 6 were currently exposed to cabergoline, and 19 had not been exposed to any dopamine agonist within the previous year. The rate of cardiac-valve regurgitation was increased with current use of pergolide (incidence-rate ratio, 7.1; 95% confidence interval [CI], 2.3 to 22.3) and cabergoline (incidence-rate ratio, 4.9; 95% CI, 1.5 to 15.6), but not with current use of other dopamine agonists.. In this study, use of the dopamine agonists pergolide and cabergoline was associated with an increased risk of newly diagnosed cardiac-valve regurgitation.

Topics: Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Cabergoline; Case-Control Studies; Cohort Studies; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Logistic Models; Male; Middle Aged; Parkinson Disease; Pergolide; Serotonin 5-HT2 Receptor Agonists; Serotonin Receptor Agonists

Ergot-derived dopamine receptor agonists, often used in the treatment of Parkinson's disease, have been associated with an increased risk of valvular heart disease.. We performed an echocardiographic prevalence study in 155 patients taking dopamine agonists for Parkinson's disease (pergolide, 64 patients; cabergoline, 49; and non-ergot-derived dopamine agonists, 42) and 90 control subjects. Valve regurgitation was assessed according to American Society of Echocardiography recommendations. The mitral-valve tenting area was also measured and used as a quantitative index for leaflet stiffening and apical displacement of leaflet coaptation.. Clinically important regurgitation (moderate to severe, grade 3 to 4) in any valve was found with significantly greater frequency in patients taking pergolide (23.4%) or cabergoline (28.6%) but not in patients taking non-ergot-derived dopamine agonists (0%), as compared with control subjects (5.6%). The relative risk for moderate or severe valve regurgitation in the pergolide group was 6.3 for mitral regurgitation (P=0.008), 4.2 for aortic regurgitation (P=0.01), and 5.6 for tricuspid regurgitation (P=0.16); corresponding relative risks in the cabergoline group were 4.6 (P=0.09), 7.3 (P<0.001), and 5.5 (P=0.12). The mean mitral tenting area was significantly greater in ergot-treated patients and showed a linear relationship with the severity of mitral regurgitation. Patients treated with ergot derivatives who had grade 3 to 4 regurgitation of any valve had received a significantly higher mean cumulative dose of pergolide or cabergoline than had patients with lower grades.. The frequency of clinically important valve regurgitation was significantly increased in patients taking pergolide or cabergoline, but not in patients taking non-ergot-derived dopamine agonists, as compared with control subjects. These findings should be considered in evaluating the risk-benefit ratio of treatment with ergot derivatives.

Topics: Aged; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve; Parkinson Disease; Pergolide; Regression Analysis; Risk; Serotonin 5-HT2 Receptor Agonists; Serotonin Receptor Agonists; Ultrasonography

To assess the effect of ergot derivatives on cardiac valves in patients with Parkinson's disease (PD).. Echocardiography was performed on 46 PD patients who used either pergolide or cabergoline (MonoPD) or both (MixPD) for a minimum of 1 year and 49 age-matched healthy controls. Valvular regurgitation was graded as mild, moderate and severe. MonoPD and MixPD groups were compared with regard to demographic features, drug profile and valvulopathy.. The PD group had a mean age of 63 years, agonist duration of 3.8 years and agonist equivalent dose of 3.5mg/day. Moderate regurgitation in all three valves was significantly more common in the PD group than the controls. Severe valvular regurgitation was not observed in either group, with the exception of one PD patient. The frequency of valvulopathy and doses of agonists did not differ between MixPD and MonoPD groups.. PD patients on dopamine ergot agonists are prone to moderate valvular regurgitation more than age-matched controls. However, the frequency of valvulopathy was similar in patients who used either one or more agonists.

Topics: Aged; Antiparkinson Agents; Aortic Valve Insufficiency; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Parkinson Disease; Pergolide; Retrospective Studies; Tricuspid Valve Insufficiency

Topics: Antiparkinson Agents; Cabergoline; Ergolines; Heart Valve Diseases; Humans; Pergolide

Topics: Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Hyperprolactinemia; Ventricular Remodeling

Topics: Antipsychotic Agents; Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Methysergide; Pergolide; Receptor, Serotonin, 5-HT2B; Retroperitoneal Fibrosis; Serotonin 5-HT2 Receptor Agonists; Serotonin Antagonists

Topics: Antiparkinson Agents; Benzothiazoles; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Male; Parkinson Disease; Patient Selection; Pergolide; Pramipexole; Research Design; Sex Factors

Used in its neurological indication, cabergoline is known to induce cardiac valve regurgitations, essentially mitral and aortic valvular diseases, by its action on the 5HT2b receptors. Until now, it was assumed that the dose and the duration of exposure were the major factors of appearance. We describe a case of aortic insufficiency which developed in a patient given low doses of cabergoline (0.5 mg weekly) for non-tumoral hyperprolactinemia. Because of previous use of appetite suppressants and of bromocriptine, the exclusive responsibility of cabergoline remained uncertain. The potential gravity of these valvular heart diseases emphasizes the importance of careful cardiologic examination before and during treatment.

Topics: Aortic Valve Insufficiency; Cabergoline; Diagnosis, Differential; Dopamine Agents; Ergolines; Female; Heart Valve Diseases; Humans; Hyperprolactinemia; Middle Aged; Receptor, Serotonin, 5-HT2B

There are a large variety of dopamine agonists available. Especially de novo patients are treated with dopamine agonists to avoid dyskinesia. Dopamine agonists can be subdivided into ergoline and non-ergoline derivatives. This distinction raises the question whether there are differences in the effects to treat symptoms, not only in the side effects between the individual dopamine agonists but also between these two groups. Pergolide is now considered a second line drug because of its particularly high tendency towards valvular heart disease. Some authors claim that all ergoline-derivatives may cause this problem, while own results do not necessarily support this view. We recommend performing echocardiography on those patients being treated with an ergot-derivative. New data support the view that all dopaminergic drugs may cause somnolence and that there is no preference for non-ergots. It may be that the number of gamblers is slightly higher among patients treated with pramipexole than in others. Dopamine agonists with a high affinity to D3 receptors have a good anti-anhedonic potency. In cell culture all dopamine agonists studied so far show neuroprotective properties in cell culture. The introduction of a slow-release formulation for ropinirole and the rotigotine and lisuride patches have opened new ways of continuous dopamine receptor stimulation. Taken together, dopamine agonists show individual properties and there are differences between ergot and non-ergot derivatives.

Topics: Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Parkinson Disease; Pulmonary Fibrosis; Retroperitoneal Fibrosis

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

Restrictive valvular heart disease has been reported in patients with Parkinson's disease treated with pergolide. However, few data are available on frequency, severity, dose dependency, and reversibility of pergolide-induced disease, nor on the pulmonary pressures of these patients. We aimed to clarify these characteristics in a large group of patients.. 78 patients with Parkinson's disease treated with pergolide and 18 never treated with an ergot-derived dopamine agonist (controls) were evaluated by echocardiography. A valvular scoring system was used, ranging from 1 (proven ergot-like restrictive valvular heart disease) to 4 (no disease). For the mitral valve, tenting areas and tenting distances were measured. Systolic pulmonary artery pressures were derived from the tricuspid regurgitant jet.. Restrictive valvular heart disease of any type was present in 26 (33%) patients in the pergolide group and none in controls (p=0.0025). Important disease (score 1 or 2) was present in 15 (19%) patients in the pergolide group and none in controls (p=0.066). Mean tenting distances and tenting areas of the mitral valve were 1.08 cm (range 0.55-2.66) and 2.39 cm2 (0.88-4.59) in the restrictive mitral valve group versus 0.63 cm (0.22-1.20) and 1.39 cm2 (0.39-3.23) in the non-restrictive group (p=0.003 and p<0.0001, respectively). Significant correlation was noted between cumulative doses of pergolide and tenting areas of the mitral valves (r=0.412, p=0.017). Mean systolic pulmonary artery pressures were 39.3 mm Hg (range 25-71) in the high-dose group versus 38.5 mm Hg (20-65) in the low-dose group (p=0.76) and 31 mm Hg (25-40) in controls (p=0.02 vs all patients given pergolide). In six patients, pergolide treatment was stopped because of restrictive valvular heart disease, in two of whom regression of disease was shown.. Restrictive valvular heart disease is not a rare finding in patients treated with pergolide. Clinicians should consider changing to a non-ergot drug if this disease is diagnosed.

Topics: Aged; Antiparkinson Agents; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Parkinson Disease; Pergolide

We report on 4 new cases of valvular heart disease in Parkinson's disease patients treated with the ergot derivative dopamine agonists pergolide and cabergoline. Noninflammatory fibrotic degeneration of cardiac valves has been reported to occur in patients with carcinoid syndrome and to occasionally complicate therapies with the anti-migraine ergot alkaloid ergotamine and methysergide and with the appetite suppressants fenfluramine and dexfenfluramine. In these cases, the pathogenesis is suspected to involve serotonin-mediated abnormal fibrogenesis by means of the 5-HT2B receptors, which are expressed in the fibroblasts of heart valves. Based on strikingly similar echocardiographic and histopathological features, we strongly suspect that ergot-derived dopamine agonists may cause a valvular heart disease nearly identical to that seen in those conditions. These cases add to a rapidly growing and worrying list of similar published reports, suggesting that we may well be facing a novel, yet unrecognized, complication of this class of agents, which are widely used not only in Parkinson's disease but also in restless legs syndrome and various common endocrine dysfunctions. Therefore, until more is known about the true prevalence of this side effect, we propose that an assessment of cardiac function be performed before and in the course of a long-term therapy with ergot derivative dopamine agonists.

Topics: Adult; Aged; Cabergoline; Carbidopa; Dopamine Agonists; Drug Combinations; Echocardiography, Transesophageal; Ergolines; Ergot Alkaloids; Female; Heart Valve Diseases; Humans; Levodopa; Male; Parkinson Disease; Pergolide

Topics: Antipsychotic Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Heart Valve Diseases; Humans; Hyperprolactinemia; Pergolide; Pulmonary Fibrosis; Risperidone

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