DOAC use persists in NVAF patients with liver disease

A knowledge gap exists on the effects of direct oral anticoagulants (DOACs), but most nonvalvular atrial fibrillation (NVAF) patients with liver disease still begin treatment with these medications, particularly apixaban and rivaroxaban, a study has found.

“[W]hile the long-term persistence with DOACs was relatively low, it was still higher than with the therapeutic alternative vitamin K antagonists (VKAs),” the researchers said.

Between 2011 and 2020, a population-based cohort of NVAF patients with liver disease initiating oral anticoagulants was assembled using the UK Clinical Practice Research Datalink.

The researchers performed logistic regression to estimate odds ratios (ORs) and 95 percent confidence intervals (CIs) of the association between patient characteristics and initiation of DOACs vs VKAs. They also used Cox proportional hazards models to gauge hazard ratios (HRs) and 95 percent CIs of the association between patient characteristics and the switch from VKAs to DOACs vs remaining on VKAs.

Finally, the authors examined the 5-year treatment persistence with DOACs vs VKAs and whether ischaemic stroke or bleeding preceded treatment cessation.

Of the 3,167 NVAF patients with liver disease, 2,247 (71 percent) initiated DOACs and 920 (29 percent) started on VKAs. DOACs initiators were more likely to have prior ischaemic stroke (OR, 1.44, 95 percent CI, 1.12‒1.85) than those on VKA but were less likely to have used antiplatelets (OR, 0.66, 96 percent CI, 0.53‒0.82). [Br J Clin Pharmacol 2022;88:994-1009]

Patients who switched to DOACs were more likely to have taken selective serotonin reuptake inhibitors (HR, 1.64, 95 percent CI, 1.13‒2.37) relative to those remaining on VKAs. At 5 years, 31 percent and 9 percent of DOAC and VKA initiators, respectively, remained persistent. Moreover, few patients presented with ischaemic stroke or bleeding before discontinuing treatment.

“The probability of DOAC vs VKA initiation in our study increased substantially over time, and every third VKA initiator eventually switched to a DOAC,” the researchers said. “Thus, combining the available evidence, it seems that after an initial phase following DOAC market approval … there has been a steep increase in the uptake of DOACs and a shift to users with a higher comorbidity burden.”

Most popular DOACs

Of note, apixaban and rivaroxaban turned out to be the most common DOACs used to initiate treatment in NVAF patients with liver disease.

However, specific recommendations for this high-risk population were not included in the guidelines because of the lack of data from trials assessing the efficacy and safety of DOACs in these patients. [Eur Heart J 2016;37:2893-2962; Circulation 2014;130:e199- e267; Can J Cardiol 2016;32:1170-1185]

In addition, recommendations from regulatory agencies were based on pharmacokinetic data and were similar for all DOACs, with severe liver dysfunction as the only contraindication. [J Am Coll Cardiol 2018;71:2162-2175]

“Thus, the predominance of apixaban and rivaroxaban in our study seems to be related to their increased use in the overall NVAF population rather than based on liver-specific considerations,” the researchers said.

“This hypothesis is also supported by the fact that apixaban and rivaroxaban were the most common DOACs also among patients with liver cirrhosis, in whom hepatic function should be even more compromised,” they added.