Liver Cirrhosis in Patients With Atrial Fibrillation: Would Oral Anticoagulation Have a Net Clinical Benefit for Stroke Prevention?

Abstract

BackgroundPatients with liver cirrhosis have been excluded from randomized clinical trials of oral anticoagulation therapy for stroke prevention in atrial fibrillation. We hypothesized that patients with liver cirrhosis would have a positive net clinical benefit for oral anticoagulation when used for stroke prevention in atrial fibrillation.Methods and ResultsThis study used the National Health Insurance Research Database in Taiwan. Among 289 559 atrial fibrillation patients aged ≥20 years, there were 10 336 with liver cirrhosis, and 9056 of them having a CHA 2 DS 2‐VASc score ≥2 were divided into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Patients with liver cirrhosis had a higher risk of ischemic stroke (hazard ratio=1.10, P=0.046) and intracranial hemorrhage (hazard ratio=1.20, P=0.043) compared with those without. Among patients with liver cirrhosis, patients taking antiplatelet therapy had a similar risk of ischemic stroke (hazard ratio=1.02, 95%CI=0.88‐1.18) compared to those without antithrombotic therapies, but the risk was significantly lowered among warfarin users (hazard ratio=0.76, 95%CI=0.58‐0.99). For intracranial hemorrhage, there were no significant differences between those untreated and those taking antiplatelet therapy or warfarin. The use of warfarin was associated with a positive net clinical benefit compared with being untreated or receiving only antiplatelet therapy.ConclusionsFor atrial fibrillation patients with liver cirrhosis in the current analysis of an observational study, warfarin use was associated with a lower risk of ischemic stroke and a positive net clinical benefit compared with nontreatment, and thus, thromboprophylaxis should be considered for such patients.

Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study

“…ILF is associated with increased bleeding risk and has been included in a bleeding risk scoring system for assessing the 1‐year risk of major bleeding associated with warfarin therapy in patients with AF 2, 3, 4. In addition, hepatitis‐related chronic liver disease and cirrhosis are prevalent in Asia and are associated with higher risks of ischemic stroke, portal vein thrombosis, intracranial hemorrhage, and variceal bleeding 5, 6, 7, 8. Non–vitamin K antagonist oral anticoagulant (NOAC) represents a major advance in stroke prevention for AF patients, offering at least equivalent efficacy and less bleeding compared with warfarin 9, 10, 11, 12.…”

Liver Disease as a Predictor of New‐Onset Atrial Fibrillation

“…Few studies have evaluated the benefit of anticoagulation systematically or in a randomized fashion. Kuo et al evaluated liver disease patients with CHA 2 DS 2 ‐VASc score ≥2 in the setting of AF and showed a reduction in ischemic stroke events in patients treated with warfarin compared with those with and without antiplatelet therapy, notably without increased intracranial hemorrhage 16. However, an increased risk of hemorrhagic stroke and intracranial hemorrhage has been reported in patients with cirrhosis as compared with those without,17, 18 and in 1 study was reported to be higher than ischemic stroke risk 19.…”

Oral anticoagulant use for stroke prevention in atrial fibrillation patients with difficult scenarios

“…Major bleeding is increased in VHD patients treated with rivaroxaban.Bioprosthetic heart valvePokorney SD, 2015 [43]Apixaban–––No difference in risk of stroke and major bleeding between the apixaban and warfarin group.Carnicelli AP, 2017 [44]Edoxaban(high-dose arm)0.37 (0.1–1.42)0.5 (0.15–1.67)–Higher-dose edoxaban has similar rates of stroke and major bleeding compared with warfarin . Lower-dose edoxaban has similar rates of stroke but lower rates of major bleeding.Edoxaban(low-dose arm)0.53 (0.16–1.78) 0.12 (0.01–0.95) –Concomitant PCIDewilde WJ, 2013 [46]warfarin plus clopidogrelIn comparison to triple therapy (warfarin plus aspirin and P2Y12 inhibitor). HR   =   0.60 (0.38–0.94) for secondary endpoint (death, myocardial infarction, stroke, target-vessel revascularization, and stent thrombosis) HR   =   0.36 (0.26–0.50) for any bleeding.Cannon CP, 2017 [47]Dabigatran 150 mg plus P2Y12 inhibitorIn comparison to triple therapy (warfarin plus aspirin and P2Y12 inhibitor).Dual-Therapy Group (110 mg), HR   =   0.52 (0.42–0.63) ; Dual-Therapy Group (150 mg), HR   = 0.72 (0.58–0.88) for major or clinically relevant non-major bleeding events.Dual-Therapy Groups (Combined), HR = 1.04 (0.84 to 1.29) for risk of thromboembolic events.Dabigatran 110 mg plus P2Y12 inhibitorGibson CM, 2016 [48]Rivaroxaban 15 mg plus P2Y12 inhibitorIn comparison to warfarin plus aspirin and P2Y12 inhibitor.Low dose Rivaroxaban Group, HR = 0.59 (0.47–0.76); very low dose Rivaroxaban Group, HR   = 0.63 (0.50–0.80) for clinically significant bleeding.Low dose Rivaroxaban Group, HR = 1.08 (0.69–1.68); very low dose Rivaroxaban Group, HR = 0.93 (0.59–1.48) for major adverse cardiovascular event (a composite of death from cardiovascular causes, myocardial infarction, or stroke)rivaroxaban 2.5 mg plus aspirin and P2Y12 inhibitorCirrhosisKuo L, 2017 [49]Warfarin 0.76 (0.58–0.99) –1.27 (0.82–1.95)Warfarin use was associated with a lower risk of ischemic stroke and positive NCB compared with non-treatment.CKD = chronic kidney disease; CI = confidence interval; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HR = Hazard ratio; ICH = intracranial hemorrhage; NCB = net clinical benefit; NOAC = Non-Vitamin K antagonist oral anticoagulants; OAC = oral anticoagulants; PCI = percutaneous coronary intervention; RR = relative risk.Bold and italic values indicate statistically significant difference between two groups.…”