Hyperprolactinemia, Parkinson's Disease
Conditions
Keywords
dopamine agonists, cabergoline, Parkinson's disease, hyperprolactinemia, epidemiology, cardiac valvulopathy
Brief summary
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
Interventions
OTHERRetrospective study-
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Fibrotic Valvular Heart Disease Per 10,000 Participant-Years of Follow-Up | Up to 12 years | 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. |
| Number of Participants With Fibrosis Per 10,000 Participant-Years of Follow-Up | Up to 12 years | 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 |
| Number of Participants With Heart Failure Per 10,000 Participant-Years of Follow-Up | Up to 12 years | Occurrence of: unspecified acute edema of lung, heart failure, acute pulmonary heart disease, or acute cor pulmonale |
| Number of Participants With All-Cause Mortality Per 10,000 Participant-Years of Follow-Up | Up to 12 years | 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. |
Participant flow
Recruitment details
Noninterventional retrospective cohort study.
Participants by arm
| Arm | Count |
|---|---|
| Dopamine Agonist (Cohort 1) Participants with Parkinson's Disease (PD)/Parkinsonism, Restless Legs Syndrome (RLS) or hyperprolactinemia (previously treated) who newly started one of the ergot-derived Dopamine Agonists (DAs): Lisuride, Cabergoline, Metergoline, Bromocriptine, Pergolide, Dihydroergocryptine mesylate, Quinagolide, Ropinirole, Pramipexole, Piribedil, or Rotigotine. | 27,812 |
| Levodopa (Cohort 2) Participants with PD/Parkinsonism or RLS who newly started treatment with Levodopa: Levodopa and decarboxylase inhibitor; Levodopa, decarboxylase inhibitor and catechol-O-methyl transferase \[COMT\] inhibitor; MeLevodopa; MeLevodopa and decarboxylase inhibitor; or EtiLevodopa and decarboxylase inhibitor and had not been treated with DAs anytime prior. | 14,669 |
| Hyperprolactinemia (Cohort 3) Participants with newly diagnosed hyperprolactinemia (excluding postpartum hyperprolactinemia), who had not been treated with DAs anytime prior. | 15,147 |
| Healthy Controls (Cohort 4) Healthy control participants matched (1:1) with participants in the DA cohort (Cohort 1) for age (exact year), gender, database and date of start of DA. | 29,311 |
| Total | 86,939 |
Baseline characteristics
| Characteristic | Dopamine Agonist (Cohort 1) | Levodopa (Cohort 2) | Hyperprolactinemia (Cohort 3) | Healthy Controls (Cohort 4) | Total |
|---|---|---|---|---|---|
| Age Continuous | 48.7 years STANDARD_DEVIATION 20.1 | 76.8 years STANDARD_DEVIATION 0.1 | 40.0 years STANDARD_DEVIATION 0.1 | 49.4 years STANDARD_DEVIATION 0.1 | 52.0 years STANDARD_DEVIATION 21.4 |
| Sex: Female, Male Female | 22084 Participants | 7666 Participants | 13398 Participants | 21992 Participants | 65140 Participants |
| Sex: Female, Male Male | 5728 Participants | 7003 Participants | 1749 Participants | 7319 Participants | 21799 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: Up to 12 years
Population: Per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dopamine Agonist (Cohort 1) | Number of Participants With All-Cause Mortality Per 10,000 Participant-Years of Follow-Up | 170 Participants/10,000 Participant-Years |
| Levodopa (Cohort 2) | Number of Participants With All-Cause Mortality Per 10,000 Participant-Years of Follow-Up | 803 Participants/10,000 Participant-Years |
| Hyperprolactinemia (Cohort 3) | Number of Participants With All-Cause Mortality Per 10,000 Participant-Years of Follow-Up | NA Participants/10,000 Participant-Years |
| Healthy Controls (Cohort 4) | Number of Participants With All-Cause Mortality Per 10,000 Participant-Years of Follow-Up | 719 Participants/10,000 Participant-Years |
Primary
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
Time frame: Up to 12 years
Population: Per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dopamine Agonist (Cohort 1) | Number of Participants With Fibrosis Per 10,000 Participant-Years of Follow-Up | 2 Participants/10,000 Participant-Years |
| Levodopa (Cohort 2) | Number of Participants With Fibrosis Per 10,000 Participant-Years of Follow-Up | 5 Participants/10,000 Participant-Years |
| Hyperprolactinemia (Cohort 3) | Number of Participants With Fibrosis Per 10,000 Participant-Years of Follow-Up | NA Participants/10,000 Participant-Years |
| Healthy Controls (Cohort 4) | Number of Participants With Fibrosis Per 10,000 Participant-Years of Follow-Up | 8 Participants/10,000 Participant-Years |
Primary
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.
Time frame: Up to 12 years
Population: Per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dopamine Agonist (Cohort 1) | Number of Participants With Fibrotic Valvular Heart Disease Per 10,000 Participant-Years of Follow-Up | 21 Participants/10,000 Participant-Years |
| Levodopa (Cohort 2) | Number of Participants With Fibrotic Valvular Heart Disease Per 10,000 Participant-Years of Follow-Up | 21 Participants/10,000 Participant-Years |
| Hyperprolactinemia (Cohort 3) | Number of Participants With Fibrotic Valvular Heart Disease Per 10,000 Participant-Years of Follow-Up | NA Participants/10,000 Participant-Years |
| Healthy Controls (Cohort 4) | Number of Participants With Fibrotic Valvular Heart Disease Per 10,000 Participant-Years of Follow-Up | 52 Participants/10,000 Participant-Years |
Primary
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
Time frame: Up to 12 years
Population: Per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dopamine Agonist (Cohort 1) | Number of Participants With Heart Failure Per 10,000 Participant-Years of Follow-Up | 69 Participants/10,000 Participant-Years |
| Levodopa (Cohort 2) | Number of Participants With Heart Failure Per 10,000 Participant-Years of Follow-Up | 161 Participants/10,000 Participant-Years |
| Hyperprolactinemia (Cohort 3) | Number of Participants With Heart Failure Per 10,000 Participant-Years of Follow-Up | NA Participants/10,000 Participant-Years |
| Healthy Controls (Cohort 4) | Number of Participants With Heart Failure Per 10,000 Participant-Years of Follow-Up | 201 Participants/10,000 Participant-Years |