Rivaroxaban vs Dabigatran for Thromboprophylaxis After Joint-replacement Surgery: Exploratory Indirect Comparison Based on Metaanalysis of Pivotal Clinical Trials

摘要

Aim To indirectly compare rivaroxaban and dabigatran forprevention of venous thromboembolism (VTE) after totalhip or knee arthroplasty (THA, TKA) based on their pivotalefficacy/safety trials embracing a total of 20 618 patients.Methods Pooled risk differences (RD) for rivaroxaban vsenoxaparin and dabigatran vs enoxaparin obtained fromseparate meta-analyses of two sets of trials were used toindirectly estimate RDs for rivaroxaban vs dabigatran.Results Primary efficacy (any VTE+all-cause mortality)and safety (major bleeding) outcomes in enoxaparin armslargely differed across similarly designed rivaroxaban anddabigatran trials (differences in venography adjudicationand bleeding events definitions). However, incidenceof symptomatic VTE and incidence of major/non-majorclinically relevant bleeding (including surgical site) wereconsistent in this respect. RDs (as percentages) for symptomaticVTE were: rivaroxaban-enoxaparin = -0.4% (95%confidence interval [CI], -0.9 to 0.05); dabigatran-enoxaparin= -0.09% (95% CI, -1.0 to 0.8); rivaroxaban-dabigatran = -0.3% (95% CI, -1.3 to 0.7; P = 0.275). RDs for major/clinicallyrelevant bleeding were rivaroxaban-enoxaparin = 0.99%(95%CI, 0.29 to 1.69); dabigatran-enoxaparin = 0.02% (95%CI, -1.0 to 1.0); rivaroxaban-dabigatran = 0.97 (95% CI, -0.43to 2.37; P = 0.085). Mortality rates (all-cause, VTE-related,bleeding-related) were very low not indicating differencesbetween any two of the three treatments.Conclusion Methodological differences disable indirectcomparisons of rivaroxaban vs dabigatran that would bebased on major efficacy/safety outcomes of their pivotaltrials. The two drugs do not seem to differ regarding incidenceof symptomatic VTE. Risk of a relevant bleedingis higher with rivaroxaban than with enoxaparin and thesame tendency exists also vs dabigatran. Direct rivaroxabanvs dabigatran comparisons in this setting are needed.