Oral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation

BACKGROUND: A number of basic research and clinical studies have led to the hypothesis that oral anticoagulants may improve the survival of patients with cancer through an antitumor effect in addition to their antithrombotic effect. OBJECTIVES: To evaluate the efficacy and safety of oral anticoagulants in patients with cancer with no therapeutic or prophylactic indication for anticoagulation. SEARCH STRATEGY: A comprehensive search for studies of anticoagulation in cancer patients including (1) a February 2010 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE, ISI the Web of Science; (2) hand search of the American Society of Clinical Oncology (starting with its first volume, 1982) and of the American Society of Hematology (starting with its 2003 issue); (3) checking of references of included studies; and (4) use of "related article" feature in PubMed. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing vitamin K antagonist or other oral anticoagulants to no intervention or placebo in cancer patients without clinical evidence of venous thromboembolism. DATA COLLECTION AND ANALYSIS: Using a standardized data form we extracted data on risk of bias, participants, interventions and outcomes of interest that included all cause mortality, venous thromboembolism, major bleeding and minor bleeding. MAIN RESULTS: Of 8187 identified citations, five RCTs fulfilled the inclusion criteria. Warfarin was the oral anticoagulant in all of these RCTs and it was compared to either placebo or no intervention. The quality of evidence was moderate for all outcomes. The effect of warfarin on reduction in mortality was not statistically significant at six months (Relative risk (RR) = 0.96; 95% CI 0.80 to 1.16), at one year (RR = 0.94; 95% CI 0.8 to 1.03) at two years (RR = 0.97; 95% CI 0.87 to 1.08) or at five years (RR 0.91; 95% CI 0.83 to 1.01). One study assessed the effect of warfarin on venous thromboembolism and showed a RR reduction of 85% (P = 0.031). Warfarin increased both major bleeding (RR = 4.24; 95% CI 1.85 to 9.68) and minor bleeding (RR = 3.34; 95% CI 1.66 to 6.74). AUTHORS' CONCLUSIONS: Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer while increasing the risk for bleeding.