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Evidence summaries

Warfarin Initiation Nomograms for Venous Thromboembolism

There is insufficient evidence on the use of a 10-mg or a 5-mg loading dose for initiation of warfarin for venous thromboembolism. Level of evidence: "D"

The quality of evidence is downgraded by study limitations (unclear allocation concealment), by inconsistency (unexplained variability in results), and by imprecise results (wide confidence intervals).

Summary

A Cochrane review [Abstract] 1 included 4 studies with a total of 494 subjects. The proportion of participants who had achieved a therapeutic INR by day 5 was higher with 10-mg warfarin nomogram compared with 5-mg warfarin normogram (table T1), although there was substantial heterogeneity (I2 = 90%). A sensitivity analysis was performed using the random-effects model, and no difference was observed (RR 1.06, 95% CI 0.52 to 2.16). Each study was analyzed separately because it was not possible to perform a subgroup analysis. One study (n=201) showed significant benefit of a 10-mg warfarin nomogram for the proportion of outpatients with VTE who had achieved a therapeutic INR by day 5 (RR 1.78, 95% CI 1.41 to 2.25; NNTB = 3, 95% CI 2 to 4); another study (n=132) showed significant benefit of a 5-mg warfarin nomogram in outpatients with VTE (RR 0.58, 95% CI 0.36 to 0.93; NNTB = 5, 95% CI 3 to 28); the third study (n=50) showed no difference (RR 1.08, 95% CI 0.65 to 1.80). No difference was observed in recurrent venous thromboembolism, in major bleeding, or in minor bleeding (table T1).

10 mg warfarin initiation nomogram compared to 5 mg warfarin initiation nomogram for venous thromboembolism.

OutcomeParticipnats (studies)Assumed risk (5-mg warfarin nomogram)Corresponding risk (10-mg warfarin nomogram)RR (95% CI)
Therapeutic INR383 (3)473 per 1000601 per 1000(497 to 729)1.27 (1.05 to 1.54)
Recurrent venous thromboembolism at 90 days312(2)17 per 100025 per 1000(7 to 95)1.48 (0.39 to 5.56)
Major bleeding at 14-90 days*494(4)17 per 100016 per 1000(4 to 58)0.97 (0.27 to 3.51)
Minor bleeding at 14-90 days243(2)50 per 100026 per 1000(8 to 92)0.52 (0.15 to 1.83)
*fall in hemoglobin of > 20 g/L or transfusion of 2 or more units of red cells
Clinical comments

Acute thromboembolism is treated with LMWH together with warfarin dose titration. LMWH treatment is effective and safe, and thus there is no hurry with warfarin titration.

Note

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