Risk factors of gastrointestinal bleeding in clopidogrel users: a nationwide population-based study.

BACKGROUND: The risk factors for gastrointestinal bleeding (GIB) in clopidogrel users have not been identified.

AIM: To clarify whether clopidogrel use is a risk factor for upper GIB (UGIB) and lower GIB (LGIB) and identify the risk factors in clopidogrel users.

METHODS: Using the National Health Insurance Research Database of Taiwan, 3238 clopidogrel users and 12,952 age-, sex-, and enrolment time-matched controls in a 1:4 ratio were extracted for comparison from a cohort dataset of 1,000,000 randomly sampled subjects. Cox proportional hazard regression models were used to identify the independent risk factors for UGIB and LGIB in all enrollees and clopidogrel users after adjustments for age, gender, comorbidity [i.e., coronary artery disease, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease (CKD), cirrhosis, uncomplicated peptic ulcer disease, and peptic ulcer bleeding (PUB)], and medications [e.g., nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, aspirin, steroids, selective serotonin reuptake inhibitors (SSRIs), warfarin and alendronate].

RESULTS: Cox proportional hazard regression analysis showed that use of clopidogrel increased the risk of UGIB [hazard ratio (HR): 3.66; 95% confidence interval (CI): 2.96-4.51] and LGIB [HR: 3.52, 95% CI: 2.74-4.52]. Age, CKD, PUB history, use of aspirin and NSAIDs were independent risk factors for UGIB in the clopidogrel users. Age, CKD, PUB history, use of aspirin and SSRIs were independent risk factors for LGIB.

CONCLUSIONS: In clopidogrel users, age, CKD, PUB history, use of aspirin and NSAIDs are independent risk factors for UGIB; age, CKD, PUB history, use of aspirin and SSRIs are independent risk factors for LGIB.