PPIs cut upper GI bleeds associated with anticoagulants
Adding a proton-pump inhibitor (PPI) to anticoagulant therapy significantly lowers the risk of hospitalizations for upper gastrointestinal (GI) tract bleeding associated with anticoagulant use, a study finds.
“Drug choice and PPI cotherapy may be important during oral anticoagulant treatment, particularly for patients with elevated risk of GI bleeding,” the researchers stated. “Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper GI tract bleeding was the highest for rivaroxaban and lowest for apixaban.”
During 754,389 anticoagulation treatment person-years without PPI cotherapy, there was significantly more incidence of hospitalization for upper GI tract bleeding for rivaroxaban compared with the other anticoagulants: apixaban (incidence rate ratios [IRR], 1.97, 95 percent confidence interval [CI], 1.73–2.25), dabigatran (IRR, 1.19, 95 percent CI, 1.08–1.32), and warfarin (IRR, 1.27, 95 percent CI, 1.19-1.35). [JAMA 2018;320:2221-2230]
On the other hand, the incidence was lowest for patients treated with apixaban, which was 39 percent lower than those treated with dabigatran (IRR, 0.61, 95 percent CI, 0.52–0.70) and 36 percent lower than those who received warfarin (IRR, 0.64, 95 percent CI, 0.57–0.73).
“Oral anticoagulants can be extremely valuable in preventing an ischaemic stroke, which is one thing you really do not want to have happen, and we can't lose sight of that,” said lead author Professor Wayne Ray of Vanderbilt University School of Medicine in Nashville, Tenessee, US. “On the other hand, they have potentially very dangerous side effects.”
“What we’ve done with this study is show that clinicians can focus on a high-risk population and significantly improve care for those patients with the addition of a PPI,” he added.
The risk of hospitalizations for upper GI tract bleeding was significantly reduced by 34 percent overall when combining PPI cotherapy with anticoagulation treatment vs no PPI cotherapy (IRR, 0.66, 95 percent CI, 0.62–0.69). For each anticoagulant analysed, the most pronounced protection against hospitalization for upper GI bleeds with the addition of PPI were seen for dabigatran (IRR, 0.49, 95 percent CI, 0.41–0.59).
Also, the protective effects of PPI against hospitalization for upper GI bleeds varied depending on a patient’s baseline GI bleeding risk: the magnitude of reduction in hospitalization incidence with PPI cotherapy grew with increasing bleeding risk.
“This risk reduction was most important among the highest risk patients where without a PPI the incidence of hospitalization for upper GI bleeding was 4 percent a year. Adding a PPI reduced that hospitalization rate to 2.8 percent per year,” Ray pointed out.
“These findings may inform assessment of risks and benefits when choosing anticoagulant agents … [and] indicate the potential benefits of a GI bleeding risk assessment before initiating anticoagulant treatment,” suggested Ray and co-authors. “Before anticoagulant therapy is started, it would be beneficial to complete a GI workup to measure patients' existing risk factors and then tailor their therapy to take into account their risk status.”
The retrospective cohort study involved 1,643,123 Medicare beneficiaries (mean age 76.4 years, 56.1 women) who initiated oral anticoagulation treatment, based on filled prescriptions. As patients who had previously been hospitalized for GI bleeding or who switched anticoagulants during the study were excluded from the analysis, the researchers cautioned against generalizing the results to other populations. They also noted that other unmeasured factors such as aspirin exposure or Helicobacter pylori infection could confound the findings.