From the Journals

Anticoagulant choice, PPI cotherapy impact risk of upper GI bleeding



Patients receiving oral anticoagulant treatment had the lowest risk of gastrointestinal bleeding when taking apixaban, compared with rivaroxaban, dabigatran, and warfarin, according to a recent study.

Further, patients who received proton pump inhibitor (PPI) cotherapy had a lower overall risk of gastrointestinal bleeding, according to Wayne A. Ray, PhD, from the department of health policy at Vanderbilt University, Nashville, Tenn., and his colleagues.

“These findings indicate the potential benefits of a gastrointestinal bleeding risk assessment before initiating anticoagulant treatment,” Dr. Ray and his colleagues wrote in their study, which was published in JAMA.

Dr. Ray and his colleagues performed a retrospective, population-based study of 1,643,123 Medicare beneficiaries (mean age, 76.4 years) who received 1,713,183 new episodes of oral anticoagulant treatment between January 2011 and September 2015. They analyzed how patients reacted to apixaban, dabigatran, rivaroxaban, or warfarin both with and without PPI cotherapy.

Overall, the risk of gastrointestinal bleeding across 754,389 person-years without PPI therapy was 115 per 10,000 person-years (95% confidence interval, 112-118) in 7,119 patients. The researchers found the risk of gastrointestinal bleeding was highest in patients taking rivaroxaban (1,278 patients; 144 per 10,000 person-years; 95% CI, 136-152) and lowest when taking apixaban (279 patients; 120 per 10,000 person-years; incidence rate ratio, 1,97; 95% CI, 1.73-2.25), compared with dabigatran (629 patients; 120 per 10,000 person-years; IRR, 1.19; 95% CI, 1.08-1.32) and warfarin (4,933 patients; 113 per 10,000 person-years; IRR, 1.27; 95% CI, 1.19-1.35). There was a significantly lower incidence of gastrointestinal bleeding for apixaban, compared with warfarin (IRR, 0.64; 95% CI, 0.57-0.73) and dabigatran (IRR, 0.61; 95% CI, 0.52-0.70).

There was a lower overall incidence of gastrointestinal bleeding when receiving PPI cotherapy (264,447 person-years; 76 per 10,000 person-years), compared with patients who received anticoagulant treatment without PPI cotherapy (IRR, 0.66; 95% CI, 0.62-0.69). This reduced incidence of gastrointestinal bleeding was also seen in patients receiving PPI cotherapy and taking 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).

The researchers noted that limitations in this study included potential misclassification of anticoagulant treatment, PPI cotherapy, and NSAIDs because of a reliance on filled prescription data; confounding by unmeasured factors such as aspirin exposure or Helicobacter pylori infection; and gastrointestinal bleeding being measured using a disease risk score.

This study was supported by a grant from the National Heart, Lung, and Blood Institute. The authors reported no relevant conflicts of interest.

SOURCE: Ray WA et al. JAMA. 2018 Dec 4. doi: 10.1001/jama.2018.17242.

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