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. 2024 Jan 9;6(1):99-113.
doi: 10.1016/j.jaccao.2023.10.009. eCollection 2024 Feb.

Comparing Anticoagulation Strategies for Venous Thromboembolism Associated With Active Cancer: A Systematic Review and Meta-Analysis

Tomohiro Fujisaki  1   2 , Daisuke Sueta  1 , Eiichiro Yamamoto  1 , Conor Buckley  3 , Guilherme Sacchi de Camargo Correia  4 , Julia Aronson  5 , Paulino Tallón de Lara  6 , Koichiro Fujisue  1 , Hiroki Usuku  1 , Kenichi Matsushita  1 , Roxana Mehran  7 , George D Dangas  7 , Kenichi Tsujita  1
Affiliations

Comparing Anticoagulation Strategies for Venous Thromboembolism Associated With Active Cancer: A Systematic Review and Meta-Analysis

Tomohiro Fujisaki et al. JACC CardioOncol. .

Abstract

Background: Current guidelines recommend several direct oral anticoagulant agents (DOACs) equally for managing cancer-associated venous thromboembolism (VTE).

Objectives: The aim of this study was to assess the efficacy and safety of DOACs in patients with active cancer.

Methods: Literature searches were conducted in PubMed, Embase, and Cochrane Central in November 2022. Randomized controlled trials investigating anticoagulation strategies (vitamin K antagonists, parenteral anticoagulation [eg, low-molecular weight heparin], and DOACs) for VTE in patients with active cancer were identified for network meta-analysis. The outcomes included recurrent VTE, recurrent pulmonary embolism, recurrent deep venous thrombosis, major bleeding, clinically relevant nonmajor bleeding (CRNMB), and a composite outcome of major bleeding or CRNMB. Pooled HRs and 95% CIs were estimated using either the HR or relative risk provided from each study. Random-effects models were used for all the analyses.

Results: Seventeen randomized controlled trials involving 6,623 patients with active cancer were included. No significant differences were found among the DOACs for efficacy outcomes (recurrent VTE, pulmonary embolism, and deep venous thrombosis). In terms of major bleeding, apixaban was similarly safe compared with dabigatran and rivaroxaban but was associated with a decreased risk compared with edoxaban (HR: 0.38; 95% CI: 0.15-0.93). Regarding CRNMB, edoxaban was similarly safe compared with apixaban but was associated with a decreased risk compared with rivaroxaban (HR: 0.31; 95% CI: 0.10-0.91). Compared with parenteral anticoagulation, apixaban was associated with a reduced risk for recurrent VTE (HR: 0.60; 95% CI: 0.38-0.93) without increasing bleeding, edoxaban was associated with an increased risk for major bleeding or CRNMB (HR: 1.35; 95% CI: 1.02-1.79), and rivaroxaban was associated with an increased risk for CRNMB (HR: 3.76; 95% CI: 1.43-9.88).

Conclusions: DOACs demonstrate comparable efficacy but exhibit different safety profiles. Apixaban may confer an antithrombotic benefit without an increased risk for bleeding, distinguishing it from other contemporary anticoagulation strategies in patients with active cancer and VTE.

Keywords: bleeding; cancer-associated thrombosis; deep venous thrombosis; direct oral anticoagulant agents; pulmonary embolism; venous thromboembolism.

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Conflict of interest statement

This study was supported by Grants-in-Aid for Scientific Research (20K17087) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funder had no role in this study. Dr Tsujita has received honoraria from Bayer Yakuhin and Daiichi Sankyo; and has received grants from Bayer Yakuhin, Boehringer Ingelheim Japan, and Daiichi Sankyo. Dr Matsushita belonged to the endowed division sponsored by Abbott Medical Japan, Boston Scientific, Cardinal Health Japan, Fides-one, Getinge, GM Medical, ITI, Japan Lifeline, Kaneka Medix, Kikuchi Medical Association, Koninklijke Philips, Medtronic Japan, Nipro, and Terumo Corporation. Dr Dangas has received research and consultant grants from Daiichi Sankyo, both to his institution. Dr Mehran has received institutional research grants from Abbott, Abiomed, Applied Therapeutics, Arena, AstraZeneca, Bayer, Biosensors, Boston Scientific, Bristol Myers Squibb, CardiaWave, CellAegis, CERC, Chiesi, Concept Medical, CSL Behring, Daiichi Sankyo, Insel Gruppe, Medtronic, Novartis Pharmaceuticals, OrbusNeich, Philips, Transverse Medical, and Zoll; has received personal fees from the American College of Cardiology, Boston Scientific, the California Institute for Regenerative Medicine, Cine-Med Research, Janssen, WebMD, and the Society for Cardiovascular Angiography and Interventions; has received consulting fees paid to the institution from Abbott, Abiomed, AM-Pharma, Alleviant Medical, Bayer, Beth Israel Deaconess, CardiaWave, CeloNova, Chiesi, Concept Medical, Daiichi Sankyo, Duke University, Idorsia Pharmaceuticals, Medtronic, Novartis, and Philips; holds equity (<1%) in Applied Therapeutics, Elixir Medical, STEL, and CONTROLRAD (spouse); and has served on the scientific advisory board for the American Medical Association and Biosensors (spouse). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Flow Diagram of Study Selection A total of 6,623 patients from 17 trials were included. RCT = randomized controlled trial.
Figure 2
Figure 2
Treatment Regimen Network for this Network Meta-Analysis The thickness of the lines between strategies corresponds to the number of patients in that comparison. VKA = vitamin K antagonist.
Figure 3
Figure 3
Results for the Primary Efficacy Outcome (Recurrent Venous Thromboembolism) The figure shows the HR and 95% CI for each treatment arm. DOAC = direct oral anticoagulant agent; VKA = vitamin K antagonist.
Figure 4
Figure 4
Results for the Primary Safety Outcome (Major Bleeding) The figure displays the HR and 95% CI for each treatment arm. Abbreviations as in Figure 3.
Central Illustration
Central Illustration
Selection of Venous Thromboembolism Anticoagulation Outcomes in Patients With Active Cancer The figure illustrates the HR and 95% CI for each treatment arm. DVT = deep venous thrombosis; PE = pulmonary embolism; VKA = vitamin K antagonist; VTE = venous thromboembolism.
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