Esomeprazole With Clopidogrel Reduces Peptic Ulcer Recurrence, Compared With Clopidogrel Alone, in Patients With Atherosclerosis

BACKGROUND & AIMS: We performed a prospective, randomized, controlled study to compare the combination of esomeprazole and clopidogrel vs clopidogrel alone in preventing recurrent peptic ulcers in patients with atherosclerosis and a history of peptic ulcers. We also investigated the effects of esomeprazole on the antiplatelet action of clopidogrel. METHODS: From January 2008 to January 2010, long-term clopidogrel users with histories of peptic ulcers who did not have peptic ulcers at an initial endoscopy examination were assigned randomly to receive the combination of esomeprazole (20 mg/day, before breakfast) and clopidogrel (75 mg/day, at bedtime), or clopidogrel alone for 6 months. A follow-up endoscopy examination was performed at the end of the sixth month and whenever severe symptoms occurred. Platelet aggregation tests were performed on days 1 and 28 for 42 consecutive patients who participated in the pharmacodynamic study. RESULTS: The cumulative incidence of recurrent peptic ulcer during the 6-month period was 1.2% among patients given the combination of esomeprazole and clopidogrel (n = 83) and 11.0% among patients given clopidogrel alone (n = 82) (difference, 9.8%; 95% confidence interval, 2.6%-17.0%; P = .009). In the group given the combination therapy, there were no differences in the percentages of aggregated platelets on days 1 and 28 (31.0% +/- 20.5% vs 30.1% +/- 16.5%). CONCLUSIONS: Among patients with atherosclerosis and a history of peptic ulcers, the combination of esomeprazole and clopidogrel reduced recurrence of peptic ulcers, compared with clopidogrel alone. Esomeprazole does not influence the action of clopidogrel on platelet aggregation.