PPI co-therapy reduces upper GI bleeding hospitalizations among patients on oral anticoagulants

The incidence of hospitalization for upper gastrointestinal tract bleeding for patients taking an anticoagulant was lower among patients who were also taking a proton pump inhibitor, according to research published in JAMA.

Wayne A. Ray, PhD, of the department of health policy at Vanderbilt University School of Medicine, and colleagues wrote that previous studies revealed that PPIs were associated with a reduced incidence for upper GI bleeding with several anticoagulants.

“PPIs, which reduce gastric acid production, promote ulcer healing, and prevent ulcer recurrence, could affect the relative safety of oral anticoagulants, particularly in high-risk patients,” they wrote. “Whether PPI co-therapy is associated with a lower incidence of anticoagulant-related serious upper gastrointestinal tract bleeding for other [non-vitamin K oral anticoagulants (NOACs)] or alters the relative upper gastrointestinal tract safety associated with individual oral anticoagulants is unknown.”

To explore this aspect of PPIs more fully, researchers performed a retrospective cohort study using 1,643,123 Medicare beneficiaries. They compared the incidence of hospitalization for upper GI tract bleeding between four different anticoagulants with and without PPI co-therapy: Eliguis (apixaban, Bristol-Myers Squibb/Pfizer), Prodaxa (dabigatran, Boehringer Ingelheim), Xarelto (rivaroxaban, Janssen) and Coumadin (warfarin, Bristol-Myers Squibb).

Researchers determined adjusted incidence and risk difference per 10,000 person-years of anticoagulant treatment.

For 754,389 treatment person-years without PPI co-therapy, the adjusted incidence of hospitalization for upper GI tract bleeding was 115 per 10,000 person years (95% CI, 112–118), which was greater than the other three anticoagulants (apixaban, 73 per 10,000 person-years; IRR = 1.97; 95% CI, 1.73–2.25; dabigatran, 120 per 10,000 person-years; IRR = 1.19; 95% CI, 1.08–1.32; and warfarin, 113 per 10,000 person-years; IRR=1.27; 95% CI, 1.19–1.35).

Compared with treatment without PPI co-therapy, risk for hospitalization among patients who were also taking PPIs (264,447 patient years) was lower overall (IRR = 0.66; 95% CI, 0.62–.069), for apixaban (IRR = 0.66; 95% CI, 0.52–0.85), dabigatran (IRR = 0.49. 95% CI, 0.41–0.59), rivaroxaban (IRR = 0.75, 95% CI, 0.68–0.84), and warfarin (IRR = 0.65, 95% CI, 0.62–0.69).

Ray and colleagues wrote that the association of both anticoagulant choice and PPI co-therapy with the risk for upper GI bleeding varied depending on a patient’s underlying gastrointestinal risk.

“The magnitude of absolute differences in incidence of hospitalization for upper gastrointestinal tract bleeding in the cohort was driven by the upper quartile of risk,” they wrote. “For these patients, the difference in the annual incidence of hospitalization for upper gastrointestinal tract bleeding between the treatment strategies with the lowest and the highest gastrointestinal safety was 2.1 hospitalizations per 100 person-years. These findings indicate the potential benefits of a gastrointestinal bleeding risk assessment before initiating anticoagulant treatment.” – by Alex Young

Disclosures: The authors report no relevant financial disclosures.

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Source:

Ray WA, et al. JAMA. 2018;doi;10.1001/jama.2018.17242.