A meta-analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment: impact on survival and bleeding complications.
BACKGROUND
Preclinical evidence suggests that anticoagulants, in particular the low-molecular-weight heparins (LMWH), exert an antitumor effect, whereas clinical trials have reported conflicting results. The authors conducted a comprehensive, systematic review and meta-analysis of the evidence from randomized controlled trials (RCTs), to evaluate the impact of anticoagulants on survival and safety in cancer patients without venous thromboembolism.


METHODS
A comprehensive systematic literature review of RCTs was performed without language restrictions through May 2006 with subsequent updates to the end of 2006, including an exhaustive search of electronic databases, major conference proceedings, article references, and content experts. Two reviewers extracted data independently. Primary study outcomes were 1-year overall mortality and all bleeding complications. Major and fatal bleeding complications were secondary outcomes.


RESULTS
Across all 11 studies that were identified, anticoagulation significantly decreased 1-year overall mortality with a relative risk (RR) of 0.905 (95% confidence interval [95% CI], 0.847-0.967; P = .003). The RR for mortality was 0.877 (95% CI, 0.789-0.975; P = .015) for LMWH, compared with an RR of 0.942 (95% CI, 0.854-1.040; P = .239) for warfarin, resulting in an absolute risk difference (ARD) of 8% for LMWH and an ARD of 3% for warfarin. Improved survival with anticoagulation may be dependent on tumor type. Major bleeding episodes occurred less frequently in patients who received LMWH (ARD, 1%) compared with patients who received warfarin (ARD, 11.5%; P < .0001). Overall, fatal bleeding occurred rarely (ARD, 0.32%; P = .542).


CONCLUSIONS
Anticoagulants, particularly LMWH, significantly improved overall survival in cancer patients without venous thrombosis while increasing the risk for bleeding complications. However, given the limitations of available data, the use of anticoagulants as antineoplastic therapy cannot be recommended until additional RCTs confirm these results.
Kuderer
Nicole M
NM
James P Wilmot Cancer Center and the Department of Medicine, University of Rochester, Rochester, NY, USA. nicole.kuderer@duke.edu
Khorana
Alok A
AA
Lyman
Gary H
GH
Francis
Charles W
CW
D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014859:Warfarin