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

Publication ,  Journal Article
Pandey, AK; Xu, K; Zhang, L; Gupta, S; Eikelboom, J; Cook, O; McIntyre, WF; Lopes, RD; Crowther, M; Belley-Côté, EP; Whitlock, RP
Published in: Thromb Haemost
March 2020

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.

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Published In

Thromb Haemost

DOI

EISSN

2567-689X

Publication Date

March 2020

Volume

120

Issue

3

Start / End Page

484 / 494

Location

Germany

Related Subject Headings

  • Warfarin
  • Thromboembolism
  • Stroke
  • Risk
  • Reference Standards
  • Randomized Controlled Trials as Topic
  • Odds Ratio
  • Myocardial Infarction
  • International Normalized Ratio
  • Humans
 

Citation

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Pandey, A. K., Xu, K., Zhang, L., Gupta, S., Eikelboom, J., Cook, O., … Whitlock, R. P. (2020). Lower versus Standard INR Targets in Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Thromb Haemost, 120(3), 484–494. https://doi.org/10.1055/s-0039-3401823
Pandey, Arjun K., Ke Xu, Li Zhang, Saurabh Gupta, John Eikelboom, Olivia Cook, William F. McIntyre, et al. “Lower versus Standard INR Targets in Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Thromb Haemost 120, no. 3 (March 2020): 484–94. https://doi.org/10.1055/s-0039-3401823.
Pandey AK, Xu K, Zhang L, Gupta S, Eikelboom J, Cook O, et al. Lower versus Standard INR Targets in Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Thromb Haemost. 2020 Mar;120(3):484–94.
Pandey, Arjun K., et al. “Lower versus Standard INR Targets in Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Thromb Haemost, vol. 120, no. 3, Mar. 2020, pp. 484–94. Pubmed, doi:10.1055/s-0039-3401823.
Pandey AK, Xu K, Zhang L, Gupta S, Eikelboom J, Cook O, McIntyre WF, Lopes RD, Crowther M, Belley-Côté EP, Whitlock RP. 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.
Journal cover image

Published In

Thromb Haemost

DOI

EISSN

2567-689X

Publication Date

March 2020

Volume

120

Issue

3

Start / End Page

484 / 494

Location

Germany

Related Subject Headings

  • Warfarin
  • Thromboembolism
  • Stroke
  • Risk
  • Reference Standards
  • Randomized Controlled Trials as Topic
  • Odds Ratio
  • Myocardial Infarction
  • International Normalized Ratio
  • Humans