1. Apart from the increased thrombosis in 3 month follow up noted with the unfractionated heparin (UFH)-vitamin K antagonist combination, all other treatment options for venous thromboembolism had similar outcomes to low molecular weight heparin (LMWH)-vitamin K antagonists with regards to recurrent thrombosis.
2. Compared to the LMWH-vitamin K antagonist combination, the use of oral anticoagulants (rivaroxaban and apixaban) appeared to decrease the risk of major bleeding episodes.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Venous thromboembolism is clinically managed with anticoagulant therapy to achieve the goal of preventing recurrent thrombosis. While many options exist for anticoagulation, the effectiveness and safety of most these treatments have not been compared.
This network meta-analyses examined the effect of various treatments on venous thromboembolism management. This study identified clinical trials that compared two different anticoagulation treatments in the setting of confirmed symptomatic acute venous thrombosis. The primary outcomes examined were recurrent venous thromboembolism and major bleeding episodes, with a median follow-up of 3 months. Most anticoagulant options demonstrated similar clinical outcomes when compared to LMWH-vitamin K antagonists. However, the UFH-vitamin K antagonist combination demonstrated an increased risk of thrombosis while rivaroxaban and apixaban appeared to decrease the risk of major bleeding episodes.
This study had a clear selection strategy and precise definitions of clinical variables and outcomes. Due to the meta-analyses approach, the sample size (nearly 45,000) was substantial for assessing the primary outcomes of recurrent venous thromboembolism and major bleeding. It further allowed for direct comparisons of several anticoagulant treatment options, which remains important for informing clinical practice. Limitations of this study include potential selection bias and heterogeneity of studies included. Majority of the studies (22) compared the use of the UFH-vitamin K antagonist combination and the LMWH-vitamin K antagonist combination, while only 6 studies compared direct oral anticoagulation with the LMWH-vitamin K antagonist, potentially biasing the analyses. Overall, however, this study highlights the comparable effectiveness of various anticoagulant treatments in the setting of acute venous thromboembolism, with the exception of the UFH-vitamin K antagonist combination.
Relevant Reading: Treatment of venous thromboembolism
In-Depth [meta-analysis]: This study compared the effect of various anticoagulant treatment options in approximately 45,000 patients diagnosed with acute venous thromboembolism. Forty-five articles were included in the meta-analyses, which associated the use of the UFH-vitamin K antagonist combination with an increased risk of recurrent thrombosis during the 3-month follow-up period. In analyzing major bleeding events, 42 studies were included. Rivaroxaban and apixaban were associated with the lowest bleeding risk (HR, 0.55 and 0.31 respectively) compared to the LMWH-vitamin K antagonist combination. Compared to all other anticoagulant options, apixaban was associated with the greatest probability of being the least harmful (88.9%).
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