Gastrointestinal Events with Clopidogrel: A Nationwide Population-Based Cohort Study

Abstract

BACKGROUND: Clopidogrel prevents cardiovascular events, but has been linked with adverse gastrointestinal (GI) complications, particularly bleeding events. OBJECTIVE: We aimed to investigate the risk of adverse GI events in patients treated with clopidogrel. DESIGN: A nationwide population-based cohort study based on linkage of three administrative registries in Denmark. PARTICIPANTS: All individuals who redeemed at least one prescription of clopidogrel from 1996 to 2008 were included as exposed subjects (n = 77,503). For each exposed subject, three matched controls were randomly selected from the background population (n = 232,510). ANALYSES: Follow-up began on January 1, 1996, and was censored on December 31, 2007, or if patients emigrated or died. The study endpoint was the occurrence of any gastritis, GI ulcer or bleeding. Analyses were adjusted for comorbidity and medication. RESULTS: Regardless of dose, adjusted odds ratios associating clopidogrel use with the study endpoint were statistically significant and followed a doseresponse pattern. The crude absolute risk of GI events were: never users: 2.2 %; <0.1 defined daily dose (DDD) of clopidogrel per day: 7.1 %; 0.1-0.39 DDD: 6.0 %; 0.4-0.79 DDD: 5.7 %; ≥0.80 DDD: 4.4 %. Adjusted odds ratios were: <0.1 DDD: 1.34, 95 % CI: 1.26-1.42; 0.1-0.39 DDD: 1.58, 95 % CI: 1.48-1.68; 0.4-0.79 DDD: 1.91, 95 % CI: 1.77-2.06; ≥0.80 DDD: 1.77, 95 % CI: 1.66-1.89, all p-values<0.01. Depending on the dose, numbers needed to harm ranged from 58 to 33 patients receiving 12 months of clopidogrel treatment. CONCLUSIONS: The well-known cardioprotective effect of clopidogrel must be carefully weighed against an increased risk of GI events.

Risk of Lower and Upper Gastrointestinal Bleeding, Transfusions, and Hospitalizations With Complex Antithrombotic Therapy in Elderly Patients

“…Similarly to our study, Grove et al 21 highlighted GI adverse events associated with clopidogrel in a nationwide Dutch population-based cohort. Their results suggested an NNH ranging from 33 to 58 patients.…”

Cytochrome allelic variants and clopidogrel metabolismin cardiovascular diseases therapy

“…However, the mono-or dual prescription option is subjective to the high risk of gastrointestinal hemorrhage, peptic ulceration, perforation and obstruction [9] [45]. The largest study done so far for patients treated with clopidogrel concluded that, clopidogrel use is associated with an increased risk of adverse gastrointestinal (GI) events such as gastritis, ulcers and bleeding, suggesting that the benefits of clopidogrel should be weighed up against an increased GI adverse risks [46]. However, given the risks of morbidity and death in patients on dual antiplatelet therapy, an expert consensus board recommends the use of proton pump inhibitors in dual antiplatelet therapy in patients who have higher risk factors for gastrointestinal bleeding [47] [9].…”

Cytochrome allelic variants and clopidogrel metabolism in cardiovascular diseases therapy

“…However, the mono-or dual prescription option is subjective to the high risk of gastrointestinal hemorrhage, peptic ulceration, perforation and obstruction [9,44]. The largest study done so far for patients treated with clopidogrel concluded that, clopidogrel use is associated with an increased risk of adverse gastrointestinal (GI) events such as gastritis, ulcers and bleeding, suggesting that the benefits of clopidogrel should be weighed up against an increased GI adverse risks [45]. However, given the risks of morbidity and death in patients on dual antiplatelet therapy, an expert consensus board recommends the use of proton pump inhibitors in dual antiplatelet therapy in patients who have higher risk factors for gastrointestinal bleeding [46,9].…”