New evidence that rivaroxaban is associated with higher rates of gastrointestinal bleeding than either apixaban or dabigatran may help guide oral anticoagulant selection.

A nationwide study from Iceland, comprising 5,868 patients commencing apixaban, dabigatran or rivaroxaban between 2014 and 2019, identified 241 GI bleeding events including 146 major bleeds.

All bleeding events identified initially by ICD-10 codes were confirmed by manual chart review.

The study, published in Annals of Internal Medicine, found rivaroxaban compared to apixaban was associated with higher rates of overall GI bleeding (3.2 vs. 2.5 events per 100 person-years; HR 1.42) and major GI bleeding (1.9 vs. 1.4 events per 100 person-years; HR 1.50).

Similarly, rivaroxaban also had higher rates of overall and major GI bleeding.

A sub-analysis of patients with AF also found rivaroxaban had higher rates of overall and major GI bleeding than apixaban or dabigatran.

“The results showed that rivaroxaban was associated with 40% to 42% higher overall risk for GIB and 49% to 50% higher risk for major GIB compared with apixaban.”

“Similarly, rivaroxaban was associated with 63% to 104% higher overall risk for GIB and 39% to 95% higher risk for major GIB compared with dabigatran. This association must be interpreted in the context of relatively wide CIs, especially for the smaller dabigatran group.”

The study said their findings were largely consistent with previous population-based registry studies.

“Why the risk for GIB increased for patients receiving rivaroxaban is not clear, but this may at least partly be due to the different pharmacokinetics of rivaroxaban, which is administered once daily, as opposed to the other 2 drugs, which are given twice daily,” the study said.

“Supporting this, 2 crossover treatment studies have demonstrated that rivaroxaban has a peak plasma concentration almost twice as high as that of apixaban.”

“Alternatively, the increased bleeding risk associated with rivaroxaban may be due to better adherence compared with the other 2 drugs, leading to more bleeding events and potentially fewer thromboembolic events.”

The study noted that data on thromboembolic or other bleeding events have not yet been obtained.

The investigators concluded that the findings may help with DOAC selection, especially for patients at high risk for GI bleeding.