Citation: O’Leary KJ, Wayne DB, Landler MP, et al. J Gen Int Med. 2009;24(11):1223-1227.
Pantoprazole Better than Double-Dose Famotidine in Secondary Prevention of Aspirin-Related Injury
Clinical question: Is a twice-daily H2-receptor antagonist (H2RA) or a once-daily proton pump inhibitor (PPI) better in patients who must continue low-dose-aspirin therapy despite aspirin-related peptic ulcer disease?
Background: Some patients with aspirin-related peptic ulcer disease require continued aspirin therapy. It often is assumed that PPIs are superior to H2RAs in secondary prevention of low-dose aspirin-related injury, although no randomized trials have specifically addressed this question.
Study design: A prospective, double-blind, randomized controlled trial.
Setting: A university hospital in Hong Kong.
Synopsis: In this trial, 160 patients with aspirin-related peptic ulcers/erosions were randomized to 48 weeks of oral famotidine (40 mg twice daily) or pantoprazole (20 mg daily) after mucosal healing and eradication of H pylori. During this time, all patients continued to receive aspirin (80 mg daily).
The rates of recurrent dyspeptic or bleeding ulcers/erosions within 48 weeks were 20% with famotidine versus 0% with pantoprazole. The rates of gastrointestinal (GI) bleeding alone were 7.7% versus 0%, respectively.
Of note, none of the five patients with GI bleeding had significant dyspepsia, which is consistent with prior reports that NSAID-induced injury might be silent.
Overall, high-dose famotidine was inferior to pantoprazole in the prevention of recurrent aspirin-related injury. These findings support the ACCF/ACG/AHA 2008 recommendation of PPIs over double-dose H2RAs in this clinical setting. It is not known, however, whether the PPI strategy extends to average GI-risk patients taking aspirin.
Furthermore, although not demonstrated in this study, it is possible that the lower rates of dyspepsia with pantoprazole might facilitate adherence to prolonged aspirin therapy.
Bottom line: High-dose famotidine was inferior to pantoprazole in the prevention of recurrent low-dose-aspirin-related injury.
Citation: Ng FH, Wong SY, Lam KF, et al. Famotidine is inferior to pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions. Gastroenterology. 2010;138
(1):82-88.
Intensive Insulin Therapy Is Not Beneficial in Corticosteroid-Induced Hyperglycemia Associated with Septic Shock
Clinical question: In septic shock treated with hydrocortisone, does intensive insulin therapy reduce in-hospital mortality compared with conventional glucose management?
Background: Corticosteroids might benefit patients with septic shock, but they also can exacerbate illness-induced hyperglycemia. It is hypothesized that normalization of blood glucose with intensive insulin might improve outcomes in these patients.
Study design: A multicenter, 2×2 factorial, randomized controlled trial.
Setting: Eleven ICUs in France.
Synopsis: In this 2×2 factorial comparison, 509 patients with septic shock treated with hydrocortisone were randomized to IV insulin, conventional insulin, fludrocortisone plus IV insulin, and fludrocortisone plus conventional insulin. The primary objective was to assess intensive IV versus conventional insulin, and a secondary objective was to assess the benefit of adding fludrocortisone to hydrocortisone therapy.
Overall, analysis showed no difference in in-hospital mortality in either of the two comparisons.
These null findings should be interpreted considering the following study limitations. In the intensive-insulin groups, there was a failure to reach target glucose levels of 80 mg/dL to 110 mg/dL (mean achieved levels 120 mg/dL to 130 mg/dL and higher). These levels overlapped to some degree with the control group, which targeted glucose levels <150 mg/dL and achieved mean levels of 140 mg/dL to 150 mg/dL.
The lack of substantial difference in glucose levels might have contributed to the null findings. Furthermore, the absolute risk reduction in the original sample-size calculations was overestimated. The result was an underpowered study, which also might have contributed to the null findings.