Cochrane for Clinicians

Putting Evidence into Practice

Anticoagulation for the Long-term Treatment of VTE in Patients with Cancer


Am Fam Physician. 2019 Jun 1;99(11):676-677.

Author disclosure: No relevant financial affiliations.

Clinical Question

What is the preferred anticoagulant for long-term prevention of recurring venous thromboembolism (VTE) in patients with cancer?

Evidence-Based Answer

Low-molecular-weight heparin (LMWH), vitamin K antagonists, and direct oral anticoagulants, when used to prevent recurrent VTE, have a similar impact on all-cause mortality. Compared with vitamin K antagonists, LMWH reduces recurrent VTE in patients with cancer (number needed to treat = 19), with similar adverse event profiles.1 (Strength of Recommendation: A, consistent, good-quality patient-oriented evidence.) Direct oral anticoagulants reduce VTE risk to the same extent as LMWH but at an increased risk of major bleeding (number needed to harm = 34).1 (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

Patients with cancer have an annual VTE risk of 1.3%, which is six times higher than patients without cancer.2 The risk of VTE recurrence in patients with cancer can reach 29% at one year, leading to recommendations for long-term anticoagulation.3 Cancer also conveys a high risk of major bleeding—up to 20% at one year for patients with both cancer and VTE.4 This Cochrane review evaluated the safety and effectiveness of long-term anticoagulation to prevent VTE recurrence in patients with cancer.1

Sixteen randomized controlled trials involving 5,167 patients with cancer and diagnostically confirmed initial VTE were identified. Patients of all ages with solid or hematologic cancers at any stage were studied. The primary outcome was all-cause mortality; secondary outcomes included recurrent symptomatic VTE and major bleeding. The review evaluated large, multicenter trials and local studies with as few as 35 patients. Most multicenter trials were multinational, whereas the single-center trials were conducted in North America or Europe. Studies varied greatly in the medications used within each class. The larger studies were funded by the sponsoring pharmaceutical company.

Five studies that included 1,781 patients compared LMWH and vitamin K antagonists. There was no difference in mortality between groups. LMWH reduced recurrent symptomatic VTE compared with vitamin K antagonists (number needed to treat = 19; 95% CI, 14 to 34) in patients with cancer, with no difference in major bleeding between the two groups. One study reported no difference in thrombocytopenia between patients receiving LMWH and those receiving vitamin K antagonists.

Four studies with a total of 1,031 patients compared direct oral anticoagulants and vitamin K antagonists and found similar mortality rates, recurrent symptomatic VTE rates, and bleeding events between the groups. Data were low quality because of imprecise reporting and inclusion criteria.

Two studies compared LMWH and direct oral anticoagulants, but only one study, which included 1,016 patients, contained data sufficient for analysis. Mortality risk was similar between the groups, and there was no significant difference in recurrent symptomatic VTE between the direct oral anticoagulant and LMWH treatment arms (relative risk = 0.69; 95% CI, 0.47 to 1.01). Patients using direct oral anticoagulants had an increased risk of major bleeding events compared with patients using LMWH (number needed to harm = 34; 95% CI, 13 to 2,439).

 Enlarge     Print



InterventionControlOutcomesNNT/NNHNumber of participants (number of studies)Quality of evidence


Vitamin K antagonists

Recurrent VTE

NNT = 19 (95% CI, 14 to 34) Favored LMWH

1,781 (5 RCTs)


Major bleeding

No difference

Direct oral anticoagulants

Vitamin K antagonists

Recurrent VTE

No difference

1,031 (4 RCTs)


Major bleeding

No difference

Direct oral anticoagulants

Author disclosure: No relevant financial affiliations.


show all references

1. Kahale LA, Hakoum MB, Tsolakian IG, et al. Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer. Cochrane Database Syst Rev. 2018;(6):CD006650....

2. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9(7):e1001275.

3. Chee CE, Ashrani AA, Marks RS, et al. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study. Blood. 2014;123(25):3972–3978.

4. Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res. 2014;133 (suppl 2):S49–S55.

5. Li A, Garcia DA, Lyman GH, Carrier M. Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): a systematic review and meta-analysis. Thromb Res. 2018;173:158–163.

6. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(17):2189–2204.

7. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report [published correction appears in Chest. 2016;150(4):988]. Chest. 2016;149(2):315–352.

8. National Institute for Health and Care Excellence (NICE). Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. Clinical guideline [CG144]. Updated November 2015. Accessed September 17, 2018.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.

A collection of Cochrane for Clinicians published in AFP is available at



Copyright © 2019 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions

CME Quiz

More in Pubmed


Mar 15, 2020

Access the latest issue of American Family Physician

Read the Issue

Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article