Thromb Haemost 2020; 120(03): 484-494
DOI: 10.1055/s-0039-3401823
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

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

Arjun K. Pandey
1  Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
,
Ke Xu
2  Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
,
Li Zhang
3  Division of Cardiac Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
,
Saurabh Gupta
3  Division of Cardiac Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
4  Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
,
John Eikelboom
5  Population Health Research Institute, Hamilton, Ontario, Canada
6  Division of Hematology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Olivia Cook
7  Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
William F. McIntyre
4  Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
5  Population Health Research Institute, Hamilton, Ontario, Canada
8  Division of Cardiology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Renato D. Lopes
9  Duke Clinical Research Institute, Durham, North Carolina, United States
10  Duke University School of Medicine, Durham, North Carolina, United States
,
Mark Crowther
4  Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
6  Division of Hematology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Emilie P. Belley-Côté
4  Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
5  Population Health Research Institute, Hamilton, Ontario, Canada
8  Division of Cardiology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Richard P. Whitlock
3  Division of Cardiac Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
4  Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
5  Population Health Research Institute, Hamilton, Ontario, Canada
› Author Affiliations
Funding None.
Further Information

Publication History

14 August 2019

01 November 2019

Publication Date:
15 January 2020 (online)

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.

Supplementary Material