The Association Between Dopamine Agonists and Cardiac Valvulopathy, Fibrosis and Other Cardiopulmonary Events

To assess the association between cabergoline and other dopamine agonists (DAs), and symptomatic, diagnosed serious cardiopulmonary disorders, including:

1. Cardiac valve regurgitation
2. Diffuse Pleural/pulmonary thickening and pericardial and retroperitoneal fibrosis
3. Heart failure
4. Total, cardiac and respiratory mortality

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease; Hyperprolactinemia
• Intervention / Treatment: Other: Retrospective study-

• Study Type: Observational
• Enrollment (Actual): 86939

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

General research practice databases or record linkage systems in Europe that provide access to original medical information. These are: The Health Information Network (THIN), Health Search Database (HSD)-THALES, the Integrated Primary Care Information (IPCI) and PHARMO-Record Linkage System (RLS) and meeting criteria for entry into any of the 4 cohorts between 1995 - 2007

Description

Inclusion Criteria:

• At least one year registered with the general practitioner (GP), one year of valid data from the GP, or the date of software conversion (if GP software systems had changed) and meeting criteria for any one of the 4 cohorts as defined.

Exclusion Criteria:

• rheumatic heart disease
• congenital heart disease: includes structural defects, congenital arrhythmias, and cardiomyopathies
• dilated cardiomyopathy (congestive cardiomyopathy
• pericardial, pleural, pulmonary or retroperitoneal fibrosis
• endocarditis or myocarditis
• carcinoid syndrome
• intravenous drug abuse
• fibrotic valvular heart disease
• pleural/pulmonary/pericardial/retroperitoneal fibroses
• use of fenfluramine or amiodarone within 3 years prior to date of diagnosis of fibrotic valvular heart disease

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; All persons who newly start one of the dopamine agonists (DA) after start of eligibility period	Other: Retrospective study-
Cohort 2; All persons who started levodopa after start of eligibility period and had not been treated with dopamine agonists anytime prior.	Other: Retrospective study-
Cohort 3; All persons with newly diagnosed hyperprolactinemia who had not been treated with dopamine agonists anytime prior.	Other: Retrospective study-
Cohort 4; healthy controls from general population matched on age, gender, index date and general practitioner (GP) practice to persons exposed to dopamine agonists	Other: Retrospective study-

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Fibrotic Valvular Heart Disease Per 10,000 Participant-Years of Follow-Up	Occurrence of: mitral stenosis with insufficiency, other unspecified mitral valve diseases, mitral or aortic valve stenosis, insufficiency, or disorders, multiple involvement of mitral and aortic valves, mitral and aortic valve diseases, unspecified, diseases of tricuspid valve, tricuspid valve disorders, specified as nonrheumatic, pulmonary valve disorders, endocarditis, valve unspecified, endomyocardial fibrosis, endocardial fibroelastosis, other primary or secondary cardiomyopathies, cardiomyopathy, functional and undiagnosed cardiac murmurs, other abnormal heart sounds.	Up to 12 years
Number of Participants With Fibrosis Per 10,000 Participant-Years of Follow-Up	Occurrence of: idiopathic retroperitoneal fibrosis, occlusion not otherwise specified (NOS) of ureter, diffuse (idiopathic) (interstitial) pulmonary fibrosis, Hamman-Rich syndrome, interstitial pneumonia (desquamative) (lymphoid), fibrosis of lung (atrophic; confluent; massive; perialveolar; peribronchial) chronic or unspecified, pulmonary or pleural fibrosis, abnormal communication between pericardial and pleural sacs, pleural fold anomaly, adhesive or constrictive pericarditis, pericardial fibrosis	Up to 12 years
Number of Participants With Heart Failure Per 10,000 Participant-Years of Follow-Up	Occurrence of: unspecified acute edema of lung, heart failure, acute pulmonary heart disease, or acute cor pulmonale	Up to 12 years
Number of Participants With All-Cause Mortality Per 10,000 Participant-Years of Follow-Up	All participants who died independent of the cause to include instantaneous death, death occurring in less than 24 hours from onset of symptoms, not otherwise explained, unattended death and other causes of ill defined morbidity and mortality. Cause of death was coded and classified as either cardiovascular or respiratory.	Up to 12 years

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: January 19, 2010
• First Submitted That Met QC Criteria: January 19, 2010
• First Posted (Estimate): January 21, 2010

Study Record Updates

• Last Update Posted (Estimate): March 23, 2011
• Last Update Submitted That Met QC Criteria: March 17, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: epidemiology; Parkinson's disease; hyperprolactinemia; cabergoline; dopamine agonists; cardiac valvulopathy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Parkinson Disease; Heart Valve Diseases; Hyperprolactinemia
• Other Study ID Numbers: A7231031