Clopidogrel use is associated with an increased prevalence of cerebral microbleeds in a stroke-free population: the Rotterdam study.
BACKGROUND
Although clopidogrel reduces the incidence of atherothrombotic events, its use is associated with an increased risk of major bleeding. Cerebral microbleeds (CMBs) are indicative of subclinical microangiopathy in the brain and may prelude symptomatic intracerebral hemorrhage. We examined the association between use of clopidogrel and CMBs in persons without a history of stroke.


RESULTS
We performed a cross-sectional analysis using data from the Rotterdam Study, a prospective population-based cohort of persons aged 45 years and older. Among 4408 stroke-free individuals who underwent brain magnetic resonance imaging for the detection of CMBs, we identified 121 ever-users and 4287 never-users of clopidogrel before magnetic resonance imaging. We used multiple logistic regression to analyze the association between clopidogrel and CMBs with adjustment for age, sex, cardiovascular risk factors, and common cardiovascular medication. Users of clopidogrel had a higher prevalence of CMBs (odd ratio 1.55, 95% CI 1.01 to 2.37) than nonusers and more often had a high number (> 4) of CMBs (odds ratio 3.19, 95% CI 1.52 to 6.72). Clopidogrel use was associated with a significantly higher prevalence of deep or infratentorial CMBs (odd ratio 1.90, 95% CI 1.05 to 3.45). Among clopidogrel users, we were unable to demonstrate differences in the prevalence of CMBs by indication of prescription, history of coronary heart disease, or common genetic variants in CYP2C19.


CONCLUSIONS
In stroke-free individuals, clopidogrel use was associated with a higher prevalence and higher number of CMBs. Whether this association is causal requires confirmation in prospective studies, especially given the small number of participants taking clopidogrel and the possibility of residual confounding in this study.
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Sirwan K L
SK
Darweesh
Maarten J G
MJ
Leening
Saloua
S
Akoudad
Daan W
DW
Loth
Albert
A
Hofman
M Arfan
MA
Ikram
Meike W
MW
Vernooij
Bruno H
BH
Stricker
D000368:Aged; D000369:Aged, 80 and over; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology*; D000077144:Clopidogrel; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D015995:Prevalence; D011446:Prospective Studies; D020521:Stroke; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
cerebral microbleed; magnetic resonance imaging; platelet inhibitor; population studies