Esomeprazole Reduces Peptic Ulcer Recurrence in Patients on Clopidogrel
Clinical question: Does esomeprazole prevent recurrent peptic ulcers in patients with atherosclerosis on clopidogrel?
Background: Although clopidogrel is sometimes used as an alternative antiplatelet agent to aspirin, a significant rate of recurrent ulcer bleeding on clopidogrel has been described. No previous prospective trial has studied whether a proton-pump inhibitor (PPI) can reduce the risk of peptic ulcer recurrence or bleeding in atherosclerotic patients on clopidogrel.
Study design: Randomized controlled trial.
Setting: A single veterans hospital in Taiwan.
Synopsis: One hundred sixty-five patients were enrolled with a past history of peptic ulcer disease, no signs of ulcer recurrence by endoscopy, and current use of clopidogrel 37.5 mg to 75 mg per day. All patients had atherosclerosis and had been on clopidogrel for at least two weeks, without aspirin, corticosteroids, anticoagulants, or recent treatment with a PPI. Patients were randomized to clopidogrel 75 mg at night (n=82) or clopidogrel 75 mg at night plus esomeprazole 20 mg before breakfast. Follow-up endoscopy was performed at six months or as needed for symptoms.
Recurrence of ulcer was found in 1.2% of patients on clopidogrel plus esomeprazole versus 11.0% in patients on clopidogrel alone (95% CI, 2.6-17.0%; P=0.009). The pharmacodynamic study revealed no significant differences in platelet aggregation within or between treatment groups on day 1 or day 28. No significant differences were seen on the incidence of ischemic events in this setting, but the trial was underpowered to draw conclusions on this outcome.
An important limitation is that the findings of this study are applicable only to patients on clopidogrel monotherapy and not dual antiplatelet therapy.
Bottom line: A significant reduction in recurrent peptic ulcers is seen with the combination of esomeprazole plus clopidogrel, versus clopidogrel alone, in patients with atherosclerosis and a history of peptic ulcer disease.
Citation: Hsu PI, Lai KH, Liu CP. Esomeprazole with clopidogrel reduces peptic ulcer recurrence, compared with clopidogrel alone, in patients with atherosclerosis. Gastroenterology. 2011;140:791-798.
ICU Quality-Improvement Project Reduces Hospital Mortality
Clinical question: Does a quality-improvement (QI) project in the ICU reduce in-hospital mortality and length of stay among elderly adults?
Background: Previous studies have shown that ICU-acquired infections are associated with increased morbidity and mortality, and QI initiatives reduce hospital-acquired infections. However, it has not been demonstrated that QI projects in the ICU reduce in-hospital mortality or length of stay.
Study design: Retrospective cohort study.
Setting: Four hundred fifty-nine Midwestern hospitals.
Synopsis: This study included 238,937 adults age >65 who were hospitalized in an ICU from 2001 to 2006 at one of 95 hospitals invited to implement the Keystone ICU Project. The control group included 1,091,547 elderly adults at one of 364 hospitals not invited to participate in the project. The Keystone ICU Project implements evidence-based practices to reduce rates of catheter-related bloodstream infections and ventilator-associated pneumonia.
Hospital mortality was not significantly reduced during initiation or implementation of the project; however, a significant reduction in hospital mortality occurred in the study group during one to 12 months post-implementation (OR=0.83 vs. 0.88, P=0.041) and 13 to 22 months post-implementation (OR=0.76 vs. 0.84, P=0.007). In contrast, length of stay did not differ significantly between the two groups, but the study was underpowered for this outcome.
The study is limited by the complexity of the Keystone ICU Project, as well as the exclusion of smaller hospitals and nonelderly adults. The study is promising because implementing a QI project in the ICU is associated with no known harms and might confer a mortality benefit at a relatively low cost.