Risk of cardiac valve regurgitation with dopamine agonist use in Parkinson's disease and hyperprolactinaemia: a multi-country, nested case-control study.
BACKGROUND
There is growing evidence that ergot dopamine agonists may induce cardiac valve regurgitation (CVR) in persons with Parkinson's disease. It is unclear whether the CVR risk is increased with ergot-dopamine agonist use in persons with hyperprolactinaemia, in whom the dose is much lower.


OBJECTIVE
The aim of the study was to explore the association between different dopamine agonists and CVR in patients with Parkinson's disease or hyperprolactinaemia.


METHODS
Nested case-control studies conducted separately in cohorts of Parkinson's disease and hyperprolactinaemia patients. Cases were patients who developed newly diagnosed CVR. Controls were CVR-free patients from the same cohorts and were matched to cases by age, sex, database and calendar year.


METHODS
Study patients were identified from over 4.5 million persons in The Health Improvement Network (THIN; UK), Health Search (Italy), and Integrated Primary Care Information (IPCI; the Netherlands) general practice databases in the years 1996-2007. The Parkinson's disease cohort included new users of dopamine agonists or levodopa, while the hyperprolactinaemia cohort included new users or non-users of dopamine agonists.


METHODS
Risk of newly diagnosed CVR with dopamine agonist use compared with levodopa use in the Parkinson's disease cohort, and dopamine agonist-naïve patients in the hyperprolactinaemia cohort.


RESULTS
In the Parkinson's disease cohort (7893 dopamine agonist users, 11 766 levodopa users), 85 incident CVR cases were identified. Increased CVR risk was observed for ergot dopamine agonists (adjusted OR [OR(adj)] 3.82; 95% CI 2.14, 6.81), but not for non-ergot dopamine agonists (OR(adj) 1.20; 95% CI 0.63, 2.29). In the hyperprolactinaemia cohort (6740 dopamine agonist users and 14 299 dopamine agonist-naïve patients), 37 CVR cases were identified during a mean follow-up of 4.5 years and 3.5 years for new users and non-users of dopamine agonists, respectively. However, no association with ever use of ergot dopamine agonists was observed (OR(adj) 0.47; 95% CI 0.20, 1.19).


CONCLUSIONS
Ergot-derived dopamine agonists are associated with an increased risk of CVR in Parkinson's disease but not in hyperprolactinaemia patients.
Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands. g.trifiro@erasmusmc.nl
Gianluca
G
Trifirò
M Mostafa
MM
Mokhles
Jeanne P
JP
Dieleman
Eva M
EM
van Soest
Katia
K
Verhamme
Giampiero
G
Mazzaglia
Ron
R
Herings
Cynthia
C
de Luise
Douglas
D
Ross
Guy
G
Brusselle
Annamaria
A
Colao
Wilhelm
W
Haverkamp
Rene
R
Schade
Guy
G
van Camp
Renzo
R
Zanettini
Miriam C
MC
Sturkenboom
D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D015331:Cohort Studies; D018491:Dopamine Agonists / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006349:Heart Valve Diseases / Q000139:chemically induced*; D006801:Humans; D006966:Hyperprolactinemia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*; D012307:Risk Factors
D000978:Antiparkinson Agents; D018491:Dopamine Agonists