Background: Peptic ulcer bleeding is usually treated endoscopically, then followed by proton pump inhibitor therapy, and the discontinuation of aspirin or other antiplatelet agents until the ulcer heals. The resulting risk of cardiovascular or cerebrovascular events and death is believed to be offset by reducing the risk of recurrent bleeding, but the true risk-benefit ratio is unknown. Sung and colleagues conducted a randomized, placebo-controlled trial to examine the effect of continuing aspirin therapy in patients being treated for peptic ulcer bleeding.
The Study: The authors recruited 156 patients with acute peptic ulcer bleeding who were already on low-dose aspirin (325 mg per day or less) for prophylaxis or treatment of cardiovascular disease. Within 24 hours of bleeding onset, all patients received endoscopic treatment with epinephrine and thermal coagulation, followed by pantoprazole (Protonix; 80-mg bolus intravenously, then 8 mg per hour intravenously for 72 hours, then 40 mg per day orally for the remainder of the study). After endoscopic hemostasis was achieved, patients were randomized to receive 80 mg per day of aspirin or placebo for eight weeks and were monitored for episodes of recurrent peptic ulcer bleeding and cardiovascular or cerebrovascular events.
Patients were excluded if they were using aspirin for primary prophylaxis; had gastric outlet obstruction or ulcer perforation; were taking corticosteroids, nonsteroidal anti-inflammatory drugs, or other anticoagulants; or if hemostasis could not be achieved.
Results: Although the 30-day incidence of recurrent ulcer bleeding was 10.3 percent in the aspirin group and 5.4 percent in the placebo group, the risk comparison was not statistically significant (hazard ratio [HR] = 1.9; confidence interval, 0.6 to 6.0). Total number of units of blood transfused and duration of hospital stay were similar between the two groups. However, the aspirin group had a significantly lower 30-day mortality rate than the placebo group (1.3 versus 9.0 percent; HR = 0.2), with similar estimates of eight-week mortality (HR = 0.2). Mortality caused by cardiovascular, cerebrovascular, or gastrointestinal complications was also lower in the aspirin group (HR = 0.2).
Conclusion: The authors conclude that continuing lowdose aspirin therapy after peptic ulcer bleeding may increase the risk of rebleeding, but it is also associated with a 12 percent reduction in all-cause mortality in comparison with placebo. The protective effect of aspirin (in combination with pantoprazole) seems to outweigh its potential gastrointestinal toxicity in these patients. The authors of this study tentatively suggest that aspirin be stopped for three to five days after the index bleed and resumed after stabilization, because most observed deaths from gastrointestinal bleeding occurred within the first few days after index bleeding. However, confirmatory studies examining the optimal time to restart antiplatelet therapy are needed.