Risk Factors of GI Bleeding in Clopidogrel Users
Risk Factors of GI Bleeding in Clopidogrel Users
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.
The major concern in the use of aspirin for the prevention of cardiovascular (CV) events is the development of peptic ulcer disease (PUD), including peptic ulcer bleeding (PUB). The patients who have a past history of PUD or its complications, who take larger doses of aspirin or combine clopidogrel with aspirin, who receive concomitant steroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-coagulants, and who have Helicobacter pylori infection are all at higher risk of developing aspirin-associated PUB. Clopidogrel is an alternative anti-platelet agent that inhibits adenosine diphosphate-induced platelet aggregation without inhibiting cyclooxygenase function and prostaglandin formation. It causes less upper gastrointestinal bleeding (UGIB) and has a higher CV safety and is commonly used for secondary CV event prevention in place of aspirin in patients who have experienced aspirin-related GI adverse events or who have an allergy to aspirin. Although clopidogrel is not safe enough for patients with aspirin-related PUB due to recurrent UGIB, anti-secretory agents such as proton pump inhibitors (PPI) can effectively decrease aspirin or clopidogrel-related UGIB.
Few studies evaluating the risk factors for UGIB and lower GIB (LGIB) in clopidogrel users have considered confounding factors such as underlying comorbidities and other ulcerogenic medications. This nationwide cohort study aimed to identify whether the use of clopidogrel increased the risk of UGIB and LGIB compared with subjects without anti-platelets, and to identify the risk factors for UGIB and LGIB in clopidogrel users after adjusting for age, gender, underlying comorbidities and certain medications.
Abstract and Introduction
Abstract
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.
Introduction
The major concern in the use of aspirin for the prevention of cardiovascular (CV) events is the development of peptic ulcer disease (PUD), including peptic ulcer bleeding (PUB). The patients who have a past history of PUD or its complications, who take larger doses of aspirin or combine clopidogrel with aspirin, who receive concomitant steroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-coagulants, and who have Helicobacter pylori infection are all at higher risk of developing aspirin-associated PUB. Clopidogrel is an alternative anti-platelet agent that inhibits adenosine diphosphate-induced platelet aggregation without inhibiting cyclooxygenase function and prostaglandin formation. It causes less upper gastrointestinal bleeding (UGIB) and has a higher CV safety and is commonly used for secondary CV event prevention in place of aspirin in patients who have experienced aspirin-related GI adverse events or who have an allergy to aspirin. Although clopidogrel is not safe enough for patients with aspirin-related PUB due to recurrent UGIB, anti-secretory agents such as proton pump inhibitors (PPI) can effectively decrease aspirin or clopidogrel-related UGIB.
Few studies evaluating the risk factors for UGIB and lower GIB (LGIB) in clopidogrel users have considered confounding factors such as underlying comorbidities and other ulcerogenic medications. This nationwide cohort study aimed to identify whether the use of clopidogrel increased the risk of UGIB and LGIB compared with subjects without anti-platelets, and to identify the risk factors for UGIB and LGIB in clopidogrel users after adjusting for age, gender, underlying comorbidities and certain medications.
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