Elsevier

The Lancet Oncology

Volume 17, Issue 10, October 2016, Pages e452-e466
The Lancet Oncology

Review
International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

https://doi.org/10.1016/S1470-2045(16)30369-2Get rights and content

Summary

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at an increased risk of developing VTE and are more likely to have a recurrence of VTE and bleeding while taking anticoagulants. Management of VTE in patients with cancer is a major therapeutic challenge and remains suboptimal worldwide. In 2013, the International Initiative on Thrombosis and Cancer (ITAC-CME), established to reduce the global burden of VTE in patients with cancer, published international guidelines for the treatment and prophylaxis of VTE and central venous catheter-associated thrombosis. The rapid global adoption of direct oral anticoagulants for management of VTE in patients with cancer is an emerging treatment trend that needs to be addressed based on the current level of evidence. In this Review, we provide an update of the ITAC-CME consensus recommendations based on a systematic review of the literature ranked according to the Grading of Recommendations Assessment, Development, and Evaluation scale. These guidelines aim to address in-hospital and outpatient cancer-associated VTE in specific subgroups of patients with cancer.

Introduction

Cancer is an independent major risk factor for venous thromboembolism (VTE), which is the second leading cause of death in medically and surgically treated patients with cancer.1 The incidence of symptomatic and asymptomatic VTE is steadily increasing in these patients2, 3, 4 who are at an increased risk of VTE recurrence and bleeding, and are more likely to use health-care resources.5, 6, 7 As an independent prognostic factor for cancer progression and death,1, 2 it has been recommended that VTE occurrence becomes a secondary endpoint in oncological trials.8

The clinical presentation of VTE—defined as deep vein thrombosis, pulmonary embolism, or central venous catheter-associated thrombosis—poses major therapeutic challenges that are further complicated by multiple cancer-related risk factors and comorbidities, which influence the choice of anticoagulation.9, 10, 11, 12 Despite the development of national clinical practice guidelines (CPGs) on VTE treatment,13, 14, 15, 16, 17, 18 substantial knowledge gaps remain.19 Preconceptions about patient tolerance and quality of life with the recommended anticoagulants need to be addressed as they hinder global CPG implementation. The International Initiative on Thrombosis and Cancer (ITAC-CME) initially published the 2013 international CPGs.20, 21 Evidence-based knowledge was translated into clinical practice with a free web-based mobile application (for iOS and Android), in English and French, to improve patient care. In 2015, direct oral anticoagulants (DOACs) were prescribed in 20% of patients with cancer in the US22 and worldwide23 despite an absence of direct evidence to support this shifting clinical practice.23 As a result, the ITAC-CME developed an update of the 2013 recommendations to address DOAC use in the treatment of VTE for patients with cancer. In this Review, we summarise those results, and provide the first evidence-based international guidelines on DOAC use in the treatment of VTE. Guidelines were developed by an independent working group of academic experts, reviewed by an expanded global advisory committee, and endorsed by the International Society on Thrombosis and Haemostasis.

Section snippets

Critical appraisal

After suitable articles were selected from the literature search, critical appraisal (appendix p 9) of the selected articles' methodological strength and clinical relevance was done independently by the methodologists (DF and JD) and then approved by the working group. Data were extracted into evidence tables and identified discrepancies were resolved by the working group. Conclusion tables that summarised the evidence for each clinical question were assembled to guide the development of the

Guideline recommendations for the treatment of established VTE

Recommendations on the treatment of established VTE for patients with cancer and the international advisory panel rankings of the guidelines can be found in panel 2.25, 26

Guideline recommendations for VTE prophylaxis in patients with cancer

Recommendations for VTE prophylaxis in patients with cancer and the corresponding international advisory panel rankings can be found in panel 3. VTE risk-assessment models are provided to guide anticoagulant-treatment decisions (panel 4).10, 89, 90, 91

VTE treatment in special clinical situations

Recommendations on VTE treatment for patients in special clinical situations can be found in panel 5.

Conclusion

Most new data from patients with cancer address VTE prophylaxis with LMWH and the effects of DOACs in VTE treatment. LMWH for the treatment and management of established VTE in patients with cancer is well demonstrated, with strong evidence for at least a 3-month treatment duration. Primary thromboprophylaxis with LMWH is also well defined in cancer surgery. The evidence is less clear in medically treated patients with cancer, particularly those receiving ambulatory systemic anticancer therapy.

Search strategy and selection criteria

The updated literature search (appendix p 3) for all studies published in French or English between November, 2010, and January, 2016, was done by the Institut National du Cancer using MEDLINE and PubMed Central databases with the following subject headings: “cancer”, “VTE”, “anticoagulant drugs”, and “devices”. Additional key articles and other clinical practice guidelines13, 15, 16, 17, 132 on overlapping clinical questions were consulted and included. The search included meta-analyses,

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