Benzodiazepine use and risk of stroke: a retrospective  population-based cohort study.
OBJECTIVE
The aim of this study was to investigate the possible association between benzodiazepine (BZD) use and risk of incident stroke by utilizing data from 2000 to 2003 from the National Health Insurance system of Taiwan.


METHODS
Study subjects consisted of 38,671 patients with new BZD use and 38,663 people without BZD use who were frequency-matched for age, sex and baseline comorbidity with BZD users. All subjects had no history of stroke. Each study patient's case was followed until a new diagnosis of stroke was made or until the patient was censored by loss to follow up, death, or termination of insurance. The study lasted until the end of 2009. A Cox proportional hazards regression model was used to estimate the incidences and hazard ratios (HR) of stroke.


RESULTS
The HR of hemorrhagic stroke was significantly lower in the BZD group when compared with the non-BZD group. For patients aged 20-39 years, the HR of ischemic stroke was significantly higher in the BZD group when compared with the non-BZD group. Compared to the non-BZD group, patients with a lower annual dosage (<1 g) or duration (<30 days) of BZD use had a lower risk of stroke in the elder group (P < 0.0001) and patients with a higher annual dosage (≥ 4 g) or duration (≥ 95 days) of BZD use had a higher risk of stroke in all age groups (P < 0.0001).


CONCLUSIONS
Our findings may suggest neuroprotection under lower-dosage BZD use and neurotoxicity under higher-dosage BZD use.
Wei-Shih
WS
Huang
Chih-Hsin
CH
Muo
Shih-Ni
SN
Chang
Yen-Jung
YJ
Chang
Chon-Haw
CH
Tsai
Chia-Hung
CH
Kao
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D002545:Brain Ischemia / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology*; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
D001569:Benzodiazepines