Kurlander JE, Barnes G, Fisher A, et al. Association of Anti-Secretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis. Am J Med. 2022 Jun 6. pii: S0002-9343(22)00433-8. doi: 10.1016/j.amjmed.2022.05.031. (Systematic review)

BACKGROUND: The role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a systematic review and meta-analysis.

METHODS: We searched Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and clinicaltrials.gov thru April 2021 for controlled randomized trials and observational studies evaluating the association of proton pump inhibitors (PPIs) or H2-receptor antagonists with overt upper gastrointestinal bleeding in patients using anticoagulants. Independent duplicate review, data extraction, and risk of bias assessment were performed. Observational studies were included only if they provided results controlled for at least 2 variables. Meta-analyses were performed using random effects models.

RESULTS: Six observational studies and 1 randomized trial were included. All but 1 study had low risk of bias. None of the studies excluded patients with concomitant aspirin or nonsteroidal anti-inflammatory drug use. For PPIs, the pooled relative risk of upper gastrointestinal bleeding was 0.67 (95% confidence interval 0.61, 0.74) with low statistical heterogeneity (I2 = 15%). Individual studies showed greater treatment effect in patients with higher risk for upper gastrointestinal bleeding (eg, nonsteroidal anti-inflammatory drug or aspirin use, elevated bleeding risk score). A single observational study evaluating the association of H2-receptor antagonists with upper gastrointestinal bleeding found a relative risk of 0.69 (95% confidence interval 0.24-2.02).

CONCLUSIONS: Evidence drawn mostly from observational studies with low risk of bias demonstrate that PPIs reduce upper gastrointestinal bleeding in patients prescribed oral anticoagulants. The benefit appears to be most clearcut and substantial in patients with elevated risk of upper gastrointestinal bleeding.

Discipline Area Score
Internal Medicine 6 / 7
Gastroenterology 6 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Hemostasis and Thrombosis 5 / 7
Comments from MORE raters

Gastroenterology rater

An extensive review and meta-analysis that proves the role of PPIs in patients on oral anticoagulants for reducing the incidence of GI bleed.

General Internal Medicine-Primary Care(US) rater

This is an examination of standard practice. Good to engage in this exercise from time to time.

General Internal Medicine-Primary Care(US) rater

I rated this higher (R=6; N=5) because of the negative press that PPIs are getting: "people are on them forever, etc" and "is there an increased cancer risk, etc." I think the choice to use them is important, if made in a clinically wise fashion.

Hemostasis and Thrombosis rater

I don't think this is new information to most anticoagulation experts.
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