Injectable blood thinners (anticoagulants) in patients with cancer

Akl EA, Gunukula S, Barba M, Yosuico VE D, van Doormaal FF, Kuipers S, Middeldorp S, Dickinson HO, Bryant A, Schünemann H

Published Online:

April 13, 2011

Research evidence suggests that blood thinners may improve the survival of patients with cancer. This benefit could be related to a direct antitumor effect in addition to preventing blood clots. In this systematic review, data from nine trials and 2857 participants suggest that injectable blood thinners reduce the risk of blood clots by about half and possibly increase the risk of major bleeding by 30%, but the effect on survival remains unclear. The main limitations of this systematic review are the relatively small number of included trials and the inclusion of different types and stages of cancer.

Abstract (click to read)

Background:

Anticoagulation may improve survival in patients with cancer through an antitumor effect in addition to the perceived antithrombotic effect.

Objectives:

To evaluate the efficacy and safety of parenteral anticoagulants in patients with cancer with no therapeutic or prophylactic indication for anticoagulation.

Search strategy:

A comprehensive search included (1) an electronic search (February 2010) of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2010, MEDLINE, EMBASE and ISI the Web of Science; (2) handsearch of conference proceedings; (3) checking of references of included studies; and (4) use of the 'related citation' feature in PubMed.

Selection criteria:

Randomized controlled trials (RCTs) assessing the benefits and harms of parenteral anticoagulation in patients with cancer but no therapeutic or prophylactic indication for anticoagulation.

Data collection and analysis:

Using a standardized form we extracted in duplicate data on methodological quality, participants, interventions and outcomes of interest including all-cause mortality, symptomatic thromboembolism, major bleeding, minor bleeding and quality of life (QoL).

Main results:

Of 8187 identified citations, nine RCTs enrolling 2857 patients fulfilled the inclusion criteria. In all included RCTs the intervention consisted of heparin (either unfractionated heparin or low molecular weight heparin). Overall, the effect of heparin therapy on mortality was not statistically significant at 12 months (risk ratio (RR) 0.93; 95% CI 0.85 to 1.02) but it was statistically significant at 24 months (RR 0.92; 95% CI 0.88 to 0.97). Heparin therapy was associated with a statistically and clinically important reduction in venous thromboembolism (RR 0.55; 95% CI 0.37 to 0.82). There were no statistically significant effects on major bleeding (RR 1.30; 95% CI 0.59 to 2.88), minor bleeding (RR 1.05; 95% 0.75 to 1.46) or QoL. The quality of evidence was high for symptomatic venous thromboembolism, moderate for mortality, major bleeding and minor bleeding, and low for QoL.

Authors' conclusions:

Heparin was associated with a significant reduction of death at 24 months but not 12 months. It was also associated with a reduction in venous thromboembolism but based on the RCTs in this review it had no significant effect on major bleeding, minor bleeding or QoL. Future research should further investigate the survival benefit of different types of anticoagulants in patients with different types and stages of cancer. The decision for a patient with cancer to start heparin therapy for survival benefit should balance the benefits and downsides and integrate the patient's values and preferences.

This record should be cited as:

Akl EA, Gunukula S, Barba M, Yosuico VE D, van Doormaal FF, Kuipers S, Middeldorp S, Dickinson HO, Bryant A, Schünemann H. Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database of Systematic Reviews 2011, Issue 4. Art. No.: CD006652. DOI: 10.1002/14651858.CD006652.pub3

Assessed as up to date:

December 6, 2010

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Primary Review Group:

Gynaecological Cancer Group

Health topics:

Cancer > Generic cancer care > Thrombo-embolism prevention & treatment

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Injectable blood thinners (anticoagulants) in patients with cancer

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