Lower versus Standard INR Targets in Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Thromb Haemost. 2020 Mar;120(3):484-494. doi: 10.1055/s-0039-3401823. Epub 2020 Jan 15.

Abstract

Background: Western guidelines recommend an international normalized ratio (INR) range of 2 to 3 when using warfarin for stroke prevention in atrial fibrillation (AF), but lower INR ranges are frequently used in East Asia. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) in AF patients comparing the effect of lower versus standard INR targets on thromboembolism, major bleeding, and mortality.

Methods: We searched Western databases including Cochrane CENTRAL, Medline, and Embase as well as Chinese databases including SinoMed, CNKI, and Wanfang Data. We pooled risk ratios (RRs) using random-effects model. We grouped INR targets in two ways: (1) any study-specific lower versus standard targets and (2) INR ranges of approximately 1.5 to 2 versus 2 to 3.

Results: Seventy-nine RCTs (n = 12,928) met eligibility criteria: 74 (n = 11,322) from East Asia and 5 (n = 1,606) from Western countries. Compared with standard targets, lower INR ranges were associated with higher rates of thromboembolism (76 RCTs, n = 12,577: 7.1% vs. 4.4%, RR 1.50, 95% confidence interval [CI] 1.29-1.74, I 2 = 0%), lower rates of major bleeding (61 RCTs, n = 10,815: 2.2% vs. 4.4%, RR 0.54, 95% CI 0.44-0.67, I 2 = 0%), and similar mortality (32 RCTs, n = 7,327: 4.8% vs. 5.2%, RR 1.00, 95% CI 0.85-1.19, I 2 = 0%). Results were similar when comparing target ranges of approximately 1.5 to 2 versus 2 to 3.

Conclusion: Moderate quality evidence suggests lower INR targets reduce bleeding but increase thromboembolism in AF. The data are dominated by East-Asian studies, limiting generalizability to Western populations. Until higher quality data demonstrate otherwise, an INR range of 2 to 3 should remain standard for thromboembolic prophylaxis in AF.

Publication types

  • Letter
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / therapeutic use
  • Atrial Fibrillation / blood*
  • Cardiology / standards*
  • Far East
  • Hemorrhage
  • Humans
  • International Normalized Ratio*
  • Myocardial Infarction / blood
  • Myocardial Infarction / complications
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Reference Standards
  • Risk
  • Stroke / blood
  • Stroke / prevention & control*
  • Thromboembolism / blood
  • Thromboembolism / complications
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Warfarin