Aspirin + PPI safer than clopidogrel if history of GI bleed
What is the best antithrombotic for patients with a history of upper gastrointestinal bleeding?
For patients with a history of bleeding peptic ulcer, the combination of aspirin and a proton pump inhibitor twice a day was safer than clopidogrel in terms of bleeding side effects. Although esomeprazole (Nexium) was used in this study, generic omeprazole 20 mg give twice a day provides nearly the same degree of acid suppression at a much lower cost. This study calls into question the overall safety of clopidogrel (Plavix), which has been claimed to not significantly increase the risk of bleeding. (LOE = 1b)
Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 2005; 352:238-44.
Study design: Randomized controlled trial (double-blinded)
Setting: Inpatient (any location) with outpatient follow-up
Clopidogrel has been recommended by the American College of Cardiology as the preferred drug for patients who require an antithrombotic agent to prevent heart disease but who also have a history of bleeding peptic ulcer. This study compared clopidogrel with the combination of aspirin and esomeprazole in this setting. Patients with a source of upper gastrointestinal bleeding (52% gastric ulcer, 34% duodenal ulcer, 8% both, 6% other erosions) who had healing confirmed by endoscopy were randomized to clopidogrel 75 mg daily plus esomeprazole placebo twice daily or aspirin 80 mg daily plus esomeprazole 20 mg twice daily. Groups were fairly well balanced at the outset, allocation was concealed, and analysis was by intention to treat. Patients were treated for 12 months. The primary outcome (hematemesis, melena, or a decrease in hemoglobin of at least 2 g/dL accompanied by endoscopic evidence of ulcer or erosion) was seen in 8.6% of the clopidogrel group and 0.7% of the aspirin plus esomeprazole group (P = .001; number needed to treat = 13). Three patients in the clopidogrel group had severe bleeding complications not related to the gastrointestinal tract, including 2 intraventricular hemorrhages, 1 of which was fatal; there were no bleeding complications in the aspirin group There were more deaths in the clopidogrel group (8 vs 4), but this difference was not statistically significant. There was no difference between groups in the likelihood of adverse cardiovascular events (9 vs 11).