JOURNAL ARTICLE
REVIEW

Warfarin initiation nomograms for venous thromboembolism

Pedro Garcia, Wilson Ruiz, Cesar Loza Munarriz
Cochrane Database of Systematic Reviews 2013 July 10, (7): CD007699
23839808

BACKGROUND: Venous thromboembolism (VTE) is a common condition in hospital patients. Considerable controversy is ongoing regarding optimal initial warfarin dosing for patients with acute deep venous thrombosis (DVT) and pulmonary embolism (PE). Achieving a therapeutic international normalized ratio (INR) with warfarin as soon as possible is important because this minimizes the duration of parenteral medication necessary to attain immediate anticoagulation, and it potentially decreases the cost and inconvenience of treatment. Although a 5-mg loading-dose nomogram tends to prevent excessive anticoagulation, a 10-mg loading-dose nomogram may achieve a therapeutic INR more quickly.

OBJECTIVES: To evaluate the efficacy of a 10-mg warfarin nomogram compared with a 5-mg warfarin nomogram among patients with VTE.

SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12). The review authors searched PubMed (last searched 10 April 2013) and LILACS (last searched 28 February 2013). In addition, the review authors contacted pharmaceutical companies.

SELECTION CRITERIA: Randomized controlled studies comparing warfarin initiation nomograms of 10 and 5 mg in patients with VTE.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. The review authors contacted study authors for additional information.

MAIN RESULTS: Four trials involving 494 participants were included. Three studies involving 383 participants provided data on the proportion of participants who had achieved a therapeutic INR by day five. Significant benefit of a 10-mg warfarin nomogram was observed (risk ratio [RR] 1.27, 95% confidence interval [CI] 1.05 to 1.54), although with substantial heterogeneity (I(2) = 90%). The review authors analyzed each study separately because it was not possible to perform a subgroup analysis. One study showed significant benefit of a 10-mg warfarin nomogram for the proportion of outpatients with VTE who had achieved a therapeutic INR by day five (RR 1.78, 95% CI 1.41 to 2.25), with the number needed to treat for an additional beneficial outcome (NNTB = 3, 95% CI 2 to 4); another study showed significant benefit of a 5-mg warfarin nomogram in outpatients with VTE (RR 0.58, 95% CI 0.36 to 0.93) with NNTB = 5 (95% CI 3 to 28); a third study showed no difference (RR 1.08, 95% CI 0.65 to 1.80). No difference was observed in recurrent venous thromboembolism (RVTE) at 90 days when the warfarin nomogram of 10 mg was compared with the warfarin nomogram of 5 mg (RR 1.48, 95% CI 0.39 to 5.56); no difference was observed in major bleeding at 14 days (RR 1.69, 95% CI 0.22 to 13.04) and at 90 days (RR 0.62, 95% CI 0.10 to 3.78). No difference was observed in minor bleeding at 14 to 90 days (RR 0.32, 95% CI 0.15 to 1.83) or in length of hospital stay (mean difference [MD] -2.30 days, 95% CI -7.96 to 3.36).

AUTHORS' CONCLUSIONS: In patients with acute thromboembolism (DVT or PE) aged 18 years or older, considerable uncertainty surrounds the use of a 10-mg or a 5-mg loading dose for initiation of warfarin to achieve an INR of 2.0 to 3.0 on the fifth day of therapy. Heterogeneity among analyzed studies limits certainty surrounding optimal warfarin initiation nomograms.

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