Comparative Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients with Chronic Liver Disease: A Systematic Review and Meta-analysis

Abstract

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia. Direct oral anticoagulants (DOACs), with superior efficacy and safety, have emerged as a promising alternative to warfarin. This systematic review and meta-analysis aimed to compare the safety and efficacy of DOACs and warfarin in patients with AF and chronic liver disease (CLD). A systematic search was undertaken in PubMed, the Cochrane Library, and Google Scholar to identify studies comparing the effectiveness of DOACs and warfarin in patients diagnosed with AF and CLD. Subsequent analyses were carried out using the random-effects model. This meta-analysis included eight studies involving 20,684 participants; baseline characteristics indicated a prevalent male presence (56.7%), with an average age of 61.63 ± 9 years. Primary outcomes demonstrated that DOACs were associated with significantly reduced all-cause mortality (relative risk [RR], 0.73; 95% confidence interval [CI], 0.56-0.95; I ² = 84%; P = .02) and ischemic stroke risk (RR, 0.62; 95% CI, 0.45-0.86; I ² = 61%; P = .004). Secondary outcomes revealed a significantly reduced risk of major bleeding with DOACs compared to warfarin, while gastrointestinal bleeding showed a non-significant decrease. Intracranial hemorrhage risk was significantly lower with DOACs compared to warfarin. DOACs demonstrate superior safety and efficacy compared to warfarin, evidenced by reduced rates of all-cause death, ischemic stroke, severe bleeding, and cerebral hemorrhage. Further randomized controlled trials are essential to enhance the evidence base for DOACs across diverse patient populations.

Keywords: Atrial fibrillation; DOACs; chronic liver disease; direct oral anticoagulants; meta-analysis; warfarin.

Figure 1:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. The figure depicts the systematic study-selection process following an initial literature search, which yielded 150 articles. Through de-duplication and a thorough review of titles and abstracts, a refined selection effort identified eight studies. Among these, seven were observational studies and one was a randomized controlled trial.

Figure 2:

All-cause mortality. The figure presents a meta-analysis incorporating data from five of the eight included studies, revealing a significantly reduced risk of all-cause mortality associated with direct oral anticoagulants compared to warfarin. Abbreviations: CI, confidence interval; DOACs, direct oral anticoagulants; IV, inverse variance; RR, risk ratio; SE, standard error.

Figure 3:

Ischemic stroke. The figure presents a meta-analysis consolidating data from six out of the eight included studies, elucidating a significantly reduced risk of ischemic stroke associated with direct oral anticoagulants compared to warfarin. Abbreviations: CI, confidence interval; DOACs, direct oral anticoagulants; IV, inverse variance; RR, risk ratio; SE, standard error.

Supplementary Figure S1:

Quality assessment of the included randomized controlled trials.

Supplementary Figure S2:

Funnel plots of primary outcomes. Funnel plots for (A) all-cause mortality and (B) ischemic stroke. Relative risk was used as an effect measure, and standard error was used as a measure of precision. The funnel plots indicated no evidence of publication bias.