Abstract: 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; moderate quality evidence), although with substantial heterogeneity (I2 = 90%). The review authors analyzed each study separately because it was not possible to perform a subgroup analysis by inpatient or outpatient status. 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, consisting of both inpatients and outpatients, showed no difference (RR 1.08, 95% CI 0.65 to 1.80). No difference was observed in recurrent venous thromboembolism 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; 3 studies, 362 participants, low quality evidence); no difference was observed in major bleeding at 14 to 90 days (RR 0.97, 95% CI 0.27 to 3.51; 4 studies, 494 participants, moderate quality evidence). No difference was observed in minor bleeding at 14 to 90 days (RR 0.52, 95% CI 0.15 to 1.83; 2 studies, 243 participants, very low quality evidence) or in length of hospital stay (mean difference (MD) -2.3 days, 95% CI -7.96 to 3.36; 1 study, 111 participants, low quality evidence). 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, mainly caused by differences in types of study participants and length of follow-up, limits certainty surrounding optimal warfarin initiation nomograms.

Plain-language summary: This review of four studies with a total of 494 participants (current until June 2015) found that in patients with acute thromboembolism 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. A benefit of 10-mg warfarin compared with 5-mg warfarin was observed for the proportion of patients with VTE who had achieved a therapeutic INR by day five but the quality of the evidence was moderate due to the differences among analyzed studies. In addition, no differences were observed between 5-mg and 10-mg nomograms for recurrent venous thromboembolism, major and minor bleeding, and length of hospital stay. Studies with high-quality evidence regarding the efficacy of 5-mg and 10-mg warfarin nomograms are needed. Quality of the evidence The quality of the evidence was moderate for therapeutic INR and major bleeding, low for recurrent VTE and length of hospital stay, and very low for minor bleeding. The main reason for downgrading the quality of the evidence was differences between the studies in types of study participants and length of follow-up.