Impact of Anticoagulation Intensity in Korean Patients with Atrial Fibrillation: Is It Different from Western Population?

Abstract

Background and Objectives: Although anticoagulation with warfarin is recommended as an international normalized ratio (INR) of prothrombin time between 2.0 and 3.0 and mean time in the therapeutic range (TTR) ≥70%, little has been proven that universal criteria might be suitable in Korean atrial fibrillation (AF) patients. Methods: We analyzed 710 patients with non-valvular AF who took warfarin. INR value and clinical outcomes were assessed during 2-year follow-up. Intensity of anticoagulation was assessed as mean INR value and TTR according to target INR range. Primary net-clinical outcome was defined as the composite of new-onset stroke and major bleeding. Secondary netclinical outcome was defined as the composite of new-onset stroke, major bleeding and death. Results: Thromboembolism was significantly decreased when mean INR was over 1.6. Major bleeding was significantly decreased when TTR was over 70% and mean INR was less than 2.6. Mean INR 1.6-2.6 significantly reduced thromboembolism (adjusted hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.19-0.85), major bleeding (HR, 0.43; 95% CI, 0.23-0.81), primary (HR, 0.50; 95% CI, 0.29-0.84) and secondary (HR, 0.45; 95% CI, 0.28-0.74) net-clinical outcomes, whereas mean INR 2.0-3.0 did not. Simultaneous satisfaction of mean INR 1.6-2.6 and TTR ≥70% was associated with significant risk reduction of major bleeding, primary and secondary net-clinical outcomes. Conclusions: Mean INR 1.6-2.6 was better than mean INR 2.0-3.0 for the prevention of thromboembolism and major bleeding. However, INR 1.6-2.6 and TTR ≥70% had similar clinical outcomes to INR 2.0-3.0 and TTR ≥70% in Korean patients with non-valvular AF.

The East Asian Paradox: An Updated Position Statement on the Challenges to the Current Antithrombotic Strategy in Patients with Cardiovascular Disease

“…A recent Korean experience suggested that mean INR 1.6 to 2.6 was better than mean INR 2.0 to 3.0 for the prevention of both thromboembolism and major bleeding in patients with nonvalvular AF, but did not focus on TTR to substantiate this conclusion. 51 Overall, DOACs in AF patients were associated with a comparable risk of ischemic events and significantly lower risk of major bleeding than warfarin. Therefore, DOACs are the preferred oral anticoagulants over warfarin in AF patients, but ICH risk in Asian patients on the same dose of DOAC (or their associated drug levels) still appeared to be relatively higher compared with non-Asian patients (►Fig.…”

“…In patients with atrial fibrillation (AF), warfarin administration is associated with a substantially higher risk of ICH in East Asian patients compared with Caucasian patients, 50,51 resulting in many clinicians adopting a lower international normalized ratio (INR) target range (e.g., INR: 1.6-2.6). However, the evidence for such a lower target INR does not support this approach; in a systematic review and evidence appraisal, lower INR targets reduce bleeding but increase thromboembolism in AF, with similar trends in East Asian and Western studies.…”

Standard-Intensity Versus Low-Intensity Anticoagulation with Warfarin in Asian Patients with Atrial Fibrillation: A Multi-Center, Randomized Controlled Trial

“… 19 In a Korean retrospective analysis based on the INR range, major bleeding rate was less developed with a mean INR less than 2.6. 13 However, a dichotomous comparison between an INR of 2.0 to 3.0 and an INR of <2.0 or >3.0 showed a similar major bleeding rate. In the present study, the risk of major bleeding was similar between an INR of 1.6 to 1.99 and an INR of 2.6 to 2.99.…”

“… 10 – 12 A recent Korean retrospective analysis for comparing between low-intensity and standard-intensity anticoagulation with warfarin demonstrated similar clinical outcomes. 13 …”

How to Overcome Social Inequalities of Oral Anticoagulation Usage in Korea?

“…Most guidelines suggested optimal level of anticoagulation with vitamin K dependent OACs. [1][2][3][4] Dose titration was done via blood sampling and measurement of serum concentration. Also, serum concentration of vitamin K-dependent OACs was easily changed by daily food or certain medications.…”