Low-intensity internal normalized ratio (INR) warfarin therapy was found to be equally as effective as standard-intensity INR warfarin in lowering the risk for thromboembolism in older patients with nonvalvular atrial fibrillation, according to the results of a systematic review and meta-analysis published in The American Journal of Cardiology.

Publication databases were searched through April 2020 for studies in which nonvalvular atrial fibrillation (NVAF) anticoagulation therapy was examined in patients ages >65 years. A total of 18 studies comprising 2105 patients were included. Low-intensity INR was defined as 1.5-2.0 (n=1058) and standard-intensity INR as 2.0-3.0 (n=1047).

The included studies were conducted in China (n=17) and Italy (n=1); 17 studies were prospective and 1 was retrospective; samples ranged from 48 to 267 patients.

The rates of thromboembolism were 7.75% among patients receiving low- and 6.19% among those treated with standard-INR warfarin. Both treatments had similar effect on reducing thromboembolism events (odds ratio [OR], 1.28; 95% CI, 0.90-1.81), and no study heterogeneity was detected (I2, 0%; Q-test P =.62).

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The rates of stroke were 5.2% and 4.82% and the rates of other thromboembolism events were 3.94% and 1.72% among patients treated with low- and standard-INR warfarin, respectively. Risks for stroke (OR, 1.09; 95% CI, 0.67-1.77) or other thromboembolism events (OR, 2.26; 95% CI, 0.89-5.79) were comparable for both treatment regimens.

Risk for thromboembolism was comparable in Chinese and Italian studies (OR, 1.44; 95% CI, 0.97-2.12 and OR, 0.75; 95% CI, 0.33-1.71, respectively), and in patients aged 65 to 74 years vs ³75 years (OR, 1.79; 95% CI, 0.83-3.86 and OR, 1.16; 95% CI, 0.78-1.73, respectively).

All-cause mortality rates were 20.2% and 16.7% among patients receiving low- and standard-INR warfarin. The effect on all-cause mortality reduction was found to be comparable for low- and standard-intensity warfarin (OR, 1.38; 95% CI, 0.94-2.02; I2, 0%; Q-test P =.53).

Patients receiving low- vs standard-intensity warfarin had reduced risks for: major (2.29% vs 7.27%, respectively) and minor bleeding (6.14% vs 17.9%, respectively). In a pooled analysis, risk for major bleeding was found to be reduced by 68% (OR, 0.32; 95% CI, 0.19-0.52; I2, 0%; Q-test P =.94) and risk for minor bleeding by 70% (OR, 0.30; 95% CI, 0.20-0.45; I2, 0%; Q-test P =.97) in patients treated with low- vs standard-intensity warfarin.

Patients aged 65 to 74 years and ³75 years had a reduced risk for major bleeding (OR, 0.22; 95% CI, 0.06-0.90 and OR, 0.34; 95% CI, 0.19-0.58, respectively). The risk for minor bleeding was also reduced in patients aged 65 to 74 years (OR, 0.3; 95% CI, 0.14-0.63) and ³75 years (OR, 0.3; 95% CI, 0.18-0.48).

Any bleeding event was more common among older Chinese vs Italian patients, and the reduced risk for any bleeding event was not replicated in the Italian study (OR, 0.56; 95% CI, 0.27-1.18).

This study was limited including lack of analysis of renal function with warfarin therapy.

“[L]ow-intensity INR of warfarin therapy is as effective as standard intensity INR therapy in reducing thromboembolic risk in patients >65 years with [nonvalvular atrial fibrillation], and has a safer profile of bleeding,” concluded the study authors.


Kang F, Ma Y, Cai A, et al. Meta-analysis evaluating the efficacy and safety of low-intensity warfarin for patients >65 years of age with non-valvular atrial fibrillation. Am J Cardiol. 2020;S0002-9149(20)31287-31302. doi:10.1016/j.amjcard.2020.12.001