A small trial showed that adding esomeprazole to clopidogrel therapy in patients with a past history of peptic ulcer disease reduced the risk of ulcers with no significant effect on measures of platelet function.

Clopidogrel is effective in reducing adverse cardiovascular events in patients with atherosclerosis, and may be an alternative to low-dose aspirin. Anti-platelet drugs increase the risk of bleeding, which is a concern in patients with a history of peptic ulceration, especially those who have had a bleeding ulcer. The preferred gastro-protective drugs are proton-pump inhibitors (PPI), however some evidence suggests that may reduce the efficacy of clopidogrel. This trial aimed to determine whether treatment with esomeprazole reduced the risk of ulcers, while using measures of platelet aggregation to confirm whether the activity of clopidogrel was reduced. Participants were patients with atherosclerosis who were receiving long-term clopidogrel treatment, who had a past history of gastro-duodenal ulcer, and who had endoscopic examination for dyspeptic symptoms or routine screening. If they had no peptic ulceration on endoscopy, they were randomised to continue clopidogrel alone or to receive open-label esomeprazole in addition to clopidogrel. Further endoscopic examination was carried out at six months or if severe symptoms occurred. Primary outcome was recurrent ulceration. A calculated sub-sample of the group had platelet aggregation testing at day 1 and day 28.

Sample size calculations suggested that 76 patients in each treatment group would give adequate statistical power, with 42 in the platelet aggregation measurement sub-group; 165 patients were randomised, 83 taking esomeprazole. Over the study period, cumulative incidence of recurrent peptic ulcer was 1.2% in the esomeprazole group and 11.0% in the control group (difference, 9.8%; 95% confidence interval, 2.6%–17.0%; P = .009). Only 1 patient (in the control group) had bleeding. In the platelet aggregation measurement subgroup, there was no significant difference between the esomeprazole and clopidogrel alone groups (percentages of aggregated platelets on days 1 and 28 31.0% ± 20.5% vs. 30.1% ± 16.5%).

The authors conclude that in this population of patients with atherosclerosis and a history of peptic ulceration, treatment with esomeprazole significantly reduced the risk of recurrent ulceration without affecting the effects of clopidogrel on platelet aggregation.