Anticoagulation
Corey Diamond, PharmD
Authors of a retrospective analysis, published in Annals of Internal Medicine on July 9, 2024, looked at the rates of major hemorrhagic and ischemic events in patients with cirrhosis who were newly prescribed apixaban and compared them with patients who were prescribed rivaroxaban or warfarin for the treatment of AFib.
Findings of the analysis revealed that patients with AFib who began taking rivaroxaban had notably higher rates of major bleeding than those taking apixaban, with similar rates of ischemic events and mortality. Additionally, patients who started warfarin versus apixaban experienced significantly higher rates of major hemorrhagic events, including hemorrhagic stroke.
AFib, which affects over 15% of patients with cirrhosis, increases the risk for severe thrombotic complications and death. Direct oral anticoagulants (DOACs), such as apixaban and rivaroxaban, are now preferred over warfarin for AFib stroke prevention due to their effectiveness and lower risk of bleeding. However, patients with cirrhosis have been excluded from key trials, leaving a gap in safety data.
“This study adds evidence that we may reserve rivaroxaban as a treatment option for [AFib] in younger patients with fewer comorbidities as a convenient once daily dosing option,” said Josh Hawks, PharmD, a clinical pharmacist education specialist for HCA Florida Healthcare, who was not involved in the research. “Conversely, clinicians may want to lean towards apixaban as a potentially safer choice in cirrhotic patients who are at higher risk for bleeding.”
The study authors noted that the findings are noteworthy, but in selecting treatment for patients, clinicians must carefully consider all risks, benefits, and alternatives.
“Future studies, including clinical trials, are still needed to compare all DOACs with one another, with warfarin, and with no anticoagulation across the full spectrum of disease,” wrote the researchers.
Design
Simon and colleagues conducted a retrospective cohort study that included outcome data from over 5,500 patients from 2013 to 2022. A trial emulation, using propensity score matching, was performed to compare the outcomes of all patients with cirrhosis and AFib who were newly initiated on apixaban, rivaroxaban, and warfarin. Patients were excluded from the analysis if their history included hospice care, valvular heart disease, end-stage renal disease, a major bleeding event within 30 days, a left atrial appendage closure procedure, any prior major bleeding or ischemic event within 60 days, or an alternative indication for an oral anticoagulant.
The researchers’ primary outcomes were major hemorrhagic events (defined as hospitalization for hemorrhagic stroke, other intracranial bleeding, major GI bleeding, or extracranial bleeding) and major ischemic events (defined as hospitalization for ischemic stroke or systemic embolism).
Apixaban versus rivaroxaban
The analysis revealed that cirrhotic patients with AFib who were initiated on rivaroxaban had a relative 47% increased risk of major hemorrhagic events compared to patients initiated on apixaban.
The researchers also found a 37% relative risk increase of major GI bleeding in the rivaroxaban pool compared to the apixaban group. These increased risks were also present when the analysis was restricted to patients taking dose reductions of these medications.
In contrast, a secondary outcome analysis found no significant differences in major ischemic events, intracranial bleeding, or all-cause mortality between the two agents.
According to the data analysis, about 30 patients with cirrhosis and AFib would need to be treated with rivaroxaban, instead of apixaban, to cause one major hemorrhagic event within a year.
Apixaban versus warfarin
The analysis found similar results when comparing initiators of apixaban and warfarin in patients with cirrhosis and AFib.
Those patients who were initiated on warfarin had a modestly significant 15% relative risk increase of major hemorrhagic events compared to apixaban.
Notably, however, patients taking warfarin had a significant 185% relative increase in intracranial bleeding. No significant differences were seen in rates of GI bleeding, major ischemic events, or all-cause mortality.
Overall, about 38 patients with cirrhosis and AFib would need to be treated with warfarin, instead of apixaban, to cause one major hemorrhagic event within a year.
Limitations
The authors of the analysis acknowledged several limitations that could impact the findings.
As a retrospective analysis, the research team relied on data that wasn’t originally collected for research purposes. Additionally, the researchers used validated algorithms to define cirrhosis and related outcomes and may have introduced misclassification bias. ■