Misoprostol heals small bowel ulcers in patients requiring aspirin

By Liz Meszaros, MDLinx
Published July 23, 2018

Key Takeaways

Misoprostol is more effective than aspirin in promoting the healing of small bowel ulcers, according to results from a recent study published in Gastroenterology.

These researchers had previously found that discontinuation of aspirin in patients with cardiothrombotic conditions may increase cardiovascular events and mortality. Continued aspirin therapy, however, increases the risk for recurrent lower gastrointestinal (GI) bleeding.

“Thus, patients requiring lifelong aspirin are left without a safe option in preventing both GI and cardiothrombotic complications. The decision on whether to resume aspirin after lower GI bleeding remains a management dilemma for clinicians, particularly in the absence of risk-mitigating therapies. It has become an urgent priority to identify a therapy to heal small bowel ulcers in aspirin users,” wrote the authors, led by Moe H. Kyaw, MD, MS, research assistant professor, Department of Medicine & Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China. 

Dr. Kyaw and colleagues conducted a prospective, double-blind, randomized, placebo-controlled study with 84 aspirin users with small bowel bleeding who needed continued aspirin therapy.  Small bowel ulcers or multiple erosions were detected upon capsule endoscopy. They sought to determine whether misoprostol can heal small bowel ulcers in patients with small bowel bleeding who require continuous aspirin therapy.

Subjects were randomized into equal groups for treatment with misoprostol (200 ug, 4 times daily) or placebo for 8 weeks. All patients continued enteric-coated aspirin therapy (100 mg/once daily).

In all, 28.6% of patients treated with misoprostol demonstrated complete healing of small bowel ulcers, compared with 9.5% of those in the placebo group (P=0.026). In a modified, intention-to-treat analysis of patients who had satisfactory follow-up capsule endoscopy studies (36 misoprostol, 40 placebo), complete healing of small bowel ulcers occurred in 33.3% and 10.0%, respectively (P=0.013).

Mean hemoglobin improvement in the misoprostol group was from 9.6 mg/dL at baseline to 12.1 mg/dL (P < 0.001), and in the placebo group, from 9.5 to 11.3 mg/dL (P < 0.001). Thus, patients in the misoprostol group had a significantly greater mean increase in hemoglobin (mean difference: 0.70 mg/dL; 95% CI: 0.05-1.36; P=0.035).

“The greater improvement in hemoglobin with misoprostol further suggested that the small bowel ulcers in this study were clinically important,” noted the authors.

Finally, the reduction in the medium number of ulcers/erosions was also significantly greater in the misoprostol group (from 6.5 to 2 vs 7 to 4, respectively; P=0.005).

Patients treated with misoprostol had more GI adverse events (AEs) than those taking placebo, with 28.6% vs 26.2%, respectively, experiencing at least one AE, and 5.3% vs 0% experiencing severe AEs.

“Our findings address the urgent need of finding a therapy for patients with small bowel bleeding who continue to require long-term aspirin. This is the first randomized study on treatment of small bowel bleeding whilst continuing aspirin. These patients often create a clinical dilemma for physicians, and previous studies were all underpowered to provide any therapeutic guidance,” wrote Dr. Kyaw and colleagues.

“Our cornerstone study has laid the foundation and provided direction for treatment of small bowel ulcers in aspirin users. It has confirmed that misoprostol is superior to placebo, but used alone will not provide full protection against aspirin on the small bowel. Together with speculation of multiple pathways leading to development of aspirin-induced ulcers, a combination therapy with misoprostol and an additional agent may provide the best chance of achieving complete mucosal healing. This should be the research direction towards eliminating the risk of small bowel ulcers from aspirin,” they concluded.

This study was supported by the Research Grant Council of Hong Kong, and presented at Digestive Disease Week, Chicago 2017.

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