Choice of Anticoagulant and Cotherapy with a PPI Affect Gastrointestinal Bleeding Risk


The risk of gastrointestinal bleeding appears to be highest with rivaroxaban and lowest with apixaban, but is reduced by cotherapy with proton pump inhibitors.

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The risk of gastrointestinal bleeding appears to be affected by both the choice of oral anticoagulant and whether patients are also taking a proton pump inhibitor (PPI), according to a new study. Incidence of hospitalization for gastrointestinal bleeding was highest in patients prescribed rivaroxaban and lowest in those prescribed apixaban. Cotherapy with a PPI was found to lower the risk of hospitalization in this retroactive study.

The study published in December in JAMA, details how researchers set out to determine whether the choice of anticoagulant drug choice and PPI cotherapy are associated with the risk of upper gastrointestinal tract bleeding.

In the retrospective cohort study of Medicare beneficiaries between January 1, 2011, and September 30, 2015, the researchers reviewed exposure to apixaban (Eliquis), dabigatran (Pradaxa), rivaroxaban (Xarelto), or warfarin with or without PPI cotherapy.

The researchers, with the Vanderbilt University School of Medicine and the Tennessee Valley Health Care System in Nashville, determined the hospitalization rates for upper gastrointestinal tract bleeding by adjusted incidence and risk difference (RD) per 10,000 person-years of anticoagulant treatment as well as incidence rate ratios (IRRs).

They found that the use of PPI cotherapy (264,447 person-years) was associated with a significantly lower overall risk of hospitalization due to gastrointestinal bleeding for all anticoagulants: an incidence rate ratio of 0.66. In 754,389 person-years of anticoagulation treatment with the four oral anticoagulants, the risk of hospitalization for upper gastrointestinal tract bleeding was highest for rivaroxaban and lowest for apixaban.

Drug choice and PPI cotherapy may be important during oral anticoagulant treatment, particularly for patients with elevated risk of gastrointestinal bleeding,” writes Wayne A. Ray, PhD, professor in the Department of Health Policy at Vanderbilt University School of Medicine, and colleagues in the JAMA article.

The adjusted overall incidence of hospitalization for upper gastrointestinal tract bleeding was 115 per 10,000 person-years. The incidence for rivaroxaban was 144 per 10,000 person-years, which was “significantly greater” than the incidence of hospitalizations for apixaban at 73 per 10,000 person-years, dabigatran at 120 per 10,000 person-years, and warfarin at 113 per 10,000 person-years.

 “For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents,” Ray writes.

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