Anticoagulation for the Treatment of Acute Venous Thromboembolism a Systematic Review and Network Meta-Analysis

Abstract

Background: There are several anticoagulation strategies are suggested for patients with acute venous thromboembolism (VTE), however proof, especially for cancer-associated VTE, is lacking of which strategy is optimal choice. We aimed to compare efficacy and safety outcomes among various anticoagulation strategies for patients with VTE using a systematic review and network meta-analysis. Methods: A systematic literature search was conducted using PUBMED, EMBASE, and Cochrane Library Central Register of Controlled Trials and clinical trial registries from inception through June 1, 2021. We search for randomized clinical trials (RCTs) comparing the recurrent VTE and bleeding outcomes of various anticoagulation strategies (low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux combined with vitamin K antagonists(VKA)); direct oral anticoagulants) for patients with acute VTE(noncancer or cancer-associated). Extraction of clinical outcomes were performed independently by two authors. A Bayesian network meta-analysis was applied to analyze the data. The primary efficacy endpoint was recurrent VTE episodes, the primary safety endpoint was major bleeding episodes. Secondary efficacy endpoints were fatal recurrent venous thromboembolism, the secondary safety endpoints were fatal bleeding episodes, all-cause mortality and major gastrointestinal bleeding. Results: 12117 citations were identified, 9850 unique citations, 54 RCTs met the inclusion criteria. Included trials recruited 49952 VTE participants with cancer or non-cancer. The findings showed that UFH-VKA likely increases recurrent VTE compared to LMWH-VKA (hazard ratio ((HR) 1·44(1·16,1·80), apixaban was probably the most effective strategy (surface under the cumulative ranking curve (SUCRA) 87·6%). Subgroup analysis for VTE patients with cancer shown that LMWH (HR 0·61(0·40,0·89)) and apixaban (HR 0·40(0·21,0·66)) were associated with less recurrent VTE events compared with LMWH-VKA. Apixaban (HR 0·44(0·24,0·73)) lowered the rate of major bleeding compared with the LMWH–VKA. The apixaban was probably the safest strategy (SUCRA 96·5%). For patients with cancer-associated acute VTE, although apixaban group experienced less major bleeding events compared with LMWH-VKA, it was not statically significant (HR 0·80(0·36,1·55)). Interpretation: Apixaban seems to be superior to other anticoagulation strategies for treatment of VTE with cancer. Funding: This work received research grant from The Second Hospital of Anhui Medical University(Hefei, Anhui 230601, China). Grant number: LBSART202007. Declaration of Interest: None to declare.