Adeel Jamil1, Umer Jamil1, Kamaldeep Singh2, Faris Khan3, Gerald Chi4. 1. From the Department of Medicine, OSF Healthcare St. Francis Medical Center, Peoria, IL. 2. Department of Medicine, Division of Inpatient Medicine, Banner University Medical Center, Medical Center, University of Arizona College of Medicine, Tucson, AZ. 3. Department of Medicine, Division of Cardiology, University of Nebraska Medical Center, Omaha, NE; and. 4. Department of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Abstract
BACKGROUND: Betrixaban and rivaroxaban are the direct anticoagulants approved in the United States for extended venous thromboembolism (VTE) prophylaxis among acutely ill medical patients. The efficacy and safety in specific subgroups remain unclear. METHODS: A meta-analysis of 3 randomized trials involving extended thromboprophylaxis with betrixaban or rivaroxaban versus enoxaparin for medically ill patients was performed to compare VTE (composite of asymptomatic proximal and symptomatic deep vein thrombosis, pulmonary embolism, or VTE-related death) and major bleeding in subgroups by baseline D-dimer, age, sex, and major medical illness on hospitalization. Risk difference (RD) was computed with the Mantel-Haenszel method by fitting a fixed-effect model. Heterogeneity of treatment effect across subgroups was examined using the nominal thresholds of P < 0.05 and I2 > 75%. RESULTS: Compared with enoxaparin, extended betrixaban or rivaroxaban reduced VTE (RD = -1.51% [95% CI, -2.32% to -0.69%]; P = 0.0003) without excess major bleeding (RD = 0.12% [-0.05% to 0.29%]; P = 0.16). A significant effect modification was observed in the subgroups by D-dimer (P = 0.004) and age (P = 0.04). Patients with D-dimer >2× upper limit of normal (ULN) experienced a greater VTE reduction (RD = -2.39% [-3.57% to -1.21%]; P < 0.0001) than those with ≤2×ULN (RD = -0.26% [-1.08% to 0.56%]; P = 0.53). Similarly, patients aged ≥75 years had a greater VTE reduction (RD = -2.29% [-3.49% to -1.09%]; P = 0.0002) than those aged <75 years (RD = -0.63% [-1.70% to 0.44%]; P = 0.25). Treatment effect was consistent across the remaining subgroups. CONCLUSIONS: A more favorable efficacy and comparable safety outcome associated with extended betrixaban or rivaroxaban were observed among medical inpatients with D-dimer >2×ULN or aged ≥75 years. D-dimer and advanced age may assist in decision-making on pharmacological thromboprophylaxis for hospitalized medical patients.
BACKGROUND:Betrixaban and rivaroxaban are the direct anticoagulants approved in the United States for extended venous thromboembolism (VTE) prophylaxis among acutely ill medical patients. The efficacy and safety in specific subgroups remain unclear. METHODS: A meta-analysis of 3 randomized trials involving extended thromboprophylaxis with betrixaban or rivaroxaban versus enoxaparin for medically ill patients was performed to compare VTE (composite of asymptomatic proximal and symptomatic deep vein thrombosis, pulmonary embolism, or VTE-related death) and major bleeding in subgroups by baseline D-dimer, age, sex, and major medical illness on hospitalization. Risk difference (RD) was computed with the Mantel-Haenszel method by fitting a fixed-effect model. Heterogeneity of treatment effect across subgroups was examined using the nominal thresholds of P < 0.05 and I2 > 75%. RESULTS: Compared with enoxaparin, extended betrixaban or rivaroxaban reduced VTE (RD = -1.51% [95% CI, -2.32% to -0.69%]; P = 0.0003) without excess major bleeding (RD = 0.12% [-0.05% to 0.29%]; P = 0.16). A significant effect modification was observed in the subgroups by D-dimer (P = 0.004) and age (P = 0.04). Patients with D-dimer >2× upper limit of normal (ULN) experienced a greater VTE reduction (RD = -2.39% [-3.57% to -1.21%]; P < 0.0001) than those with ≤2×ULN (RD = -0.26% [-1.08% to 0.56%]; P = 0.53). Similarly, patients aged ≥75 years had a greater VTE reduction (RD = -2.29% [-3.49% to -1.09%]; P = 0.0002) than those aged <75 years (RD = -0.63% [-1.70% to 0.44%]; P = 0.25). Treatment effect was consistent across the remaining subgroups. CONCLUSIONS: A more favorable efficacy and comparable safety outcome associated with extended betrixaban or rivaroxaban were observed among medical inpatients with D-dimer >2×ULN or aged ≥75 years. D-dimer and advanced age may assist in decision-making on pharmacological thromboprophylaxis for hospitalized medical patients.