Five RCTs with a total of 1,522 participants were included.
All of the studies had blind outcome assessment, two used a double-blind design, and four accounted for all randomised patients. There was no statistically-significant evidence of heterogeneity in the study results for any of the outcomes evaluated.
There were no statistically significant differences in the frequency of recurrent venous thromboembolism between once- and twice-daily therapy. The OR was 0.82 (95% CI: 0.26, 2.49, p=0.8) for symptomatic recurrent venous thromboembolism at 10 days (5 RCTs), 0.85 (95% CI: 0.48, 1.49, p=0.85) for symptomatic recurrent venous thromboembolism at 3 months (2 RCTs), and 1.34 (95% CI: 0.31, 6.68, p=0.8) for asymptomatic recurrent venous thromboembolism at 10 days (3 RCTs). There was also no statistically-significant difference in the change in the extent of venous thromboembolism.
There were no statistically-significant differences in major, minor or total bleeding between once- and twice-daily therapy. The OR was 0.90 (95% CI: 0.62, 1.29, p=0.5) for total bleeds at 10 days (5 RCTs). Three episodes of fatal bleeding occurred within 10 days, all of which were in patients who had been treated with once-daily therapy (p=0.12).
There were no statistically-significant differences in mortality between once- and twice-daily therapy. The OR was 6.73 (95% CI: 0.85, 305, p=0.07) for mortality at 10 days (5 RCTs) and 1.05 (95% CI: 0.53, 209, p=0.9) for mortality at 3 months (2 RCTs).