Gastroenterology

Gastroenterology

Volume 140, Issue 3, March 2011, Pages 791-798.e2
Gastroenterology

Clinical—Alimentary Tract
Esomeprazole With Clopidogrel Reduces Peptic Ulcer Recurrence, Compared With Clopidogrel Alone, in Patients With Atherosclerosis

https://doi.org/10.1053/j.gastro.2010.11.056Get rights and content

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 August 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.

Section snippets

Study Population

This open-labeled trial was conducted at the Kaohsiung Veterans General Hospital in Taiwan in accordance with the principles of good clinical practice from the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of the Kaohsiung Veterans General Hospital. All patients gave written informed consent before participating in the study. This trial is registered as a standard randomized Clinical Trial (ClinicalTrials.gov.identifier: NCT01138969).

We screened for eligible

Patients

From August 2008 to January 2010, we screened 253 consecutive patients who had a past history of gastroduodenal ulcer and underwent endoscopy with dyspeptic symptoms while receiving clopidogrel 75 or 37.5 mg/day, and a total of 165 of these patients were enrolled. Eighty-eight patients were excluded. Supplementary Figure 1 shows the trial profile.

All 165 randomized patients received at least one dose and were included in the ITT analysis (esomeprazole plus clopidogrel, n = 83; clopidogrel, n =

Discussion

The current study showed 11.0% of the patients with a peptic ulcer history who took clopidogrel for the prevention of ischemic events had recurrent peptic ulcer during a 6-month follow-up period.

The data indicate that a significant number of atherosclerotic patients who have a past history of peptic ulcers develop recurrent peptic ulcers during clopidogrel use. Two prospective randomized trials showed that the cumulative incidence of recurrent bleeding or ulcer complications during a 12-month

Acknowledgments

The authors are indebted to Drs F. W. Tsay, H. M. Wang, C. C. Lee, K. M. Wang, S. N. Chang, and J. L. Ou for recruiting the patients and performing the endoscopies; to the study nurses at the Kaohsiung Veterans General Hospital; to Professor L. P. Ger for statistical calculations; and to Professor D. Y. Graham for his review.

The registration number for this study is NCT01138969.

The statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary

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    Conflicts of interest The authors disclose no conflicts.

    Funding This study was funded by research grant VGHKS99-020 from the Research Fund of the Kaohsiung Veterans General Hospital.

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