Four randomised controlled trials (14,065 patients, range 1,471 to 5,765) were included: one phase II and three phase III studies. All the trials were of good quality (Jadad score 5).
Thromboprophylaxis with apixaban compared to enoxaparin was associated with significantly fewer venous thromboembolism and all-cause mortality (RR 0.63, 95% CI 0.42 to 0.95; 8,346 patients). There was evidence of high statistical heterogeneity (Ι²=84%).
There were no significant differences between thromboprophylaxis with apixaban and enoxaparin in safety outcomes for incidence of bleeding events: major bleeding (RR 0.76, 95% CI 0.43 to 1.33; 11,525 patients), clinically relevant non-major bleeding (RR 0.83, 95% CI 0.69 to 1.01; 11,525 patients) and minor bleeding (RR 0.93, 95% CI 0.79 to 1.09; 11,828 patients). There was evidence of statistical heterogeneity for major bleeding (Ι²=45%).
Apixaban was associated with significantly fewer total bleeding compared to enoxaparin (RR 0.88, 95% CI 0.79 to 0.99, Ι²=0%; 11,828 patients).
There were no significant differences between thromboprophylaxis with apixaban and enoxaparin in all secondary efficacy outcomes: major venous thromboembolism (Ι²=64%), non-fatal pulmonary embolism (Ι²=46%) and mortality (Ι²=0%). Sensitivity analyses did not alter overall treatment effects. The authors stated that there was no evidence of publication bias from the funnel plot (data not reported).