Table 2.
Apixaban clinical trial data for VTE
| Study | Year | Design | Study population | Intervention | Comparator | Primary efficacy outcome (apixaban vs comparator) | Primary safety outcome | Follow-up (years) | Authors conclusions |
|---|---|---|---|---|---|---|---|---|---|
| ADVANCE-119 | 2009 | Multicenter, randomized, double-blind, double-dummy, noninferiority and superiority | TKR | Apixaban 2.5 mg twice daily | Enoxaparin 30 mg every 12 hours | Composite of all cause VTE (symptomatic and asymptomatic DVT, nonfatal PE) and all-cause death: 9.0% vs 8.8% (RR 1.02, 95% CI 0.78–1.32) | Major bleeding: 0.7% vs 1.4% (P=0.05) Composite (major bleeding and clinically relevant nonmajor bleeding): 2.9% vs 4.3% (P=0.03) |
60 days after cessation of study drug | Efficacy: noninferiority not established Safety: lower rates of clinically relevant bleeding compared to LMWH |
| ADVANCE-220 | 2010 | Multicenter, randomized, double-blind, noninferiority and superiority | TKR | Apixaban 2.5 mg twice daily | Enoxaparin 40 mg daily | Composite of all VTE and all-cause death: 15.1% vs 24.4% (RR 0.62, 95% CI 0.51–0.74) | Major bleeding: 0.6% vs 0.9% (P=0.3014) | 60 days after cessation of study drug | Efficacy: noninferiority established; superiority established compared to LMWH Safety: no difference in major bleeding between the two treatment groups |
| ADVANCE-323 | 2010 | Multicenter, randomized, double-blind, double-dummy, noninferiority and superiority | THR | Apixaban 2.5 mg twice daily | Enoxaparin 40 mg daily | Composite of all VTE and all-cause death: 1.4% vs 3.9% (RR 0.36, 95% CI 0.22–0.54) | Major bleeding: 0.8% vs 0.7% (P=0.54) Composite (major bleeding and clinically relevant nonmajor bleeding): 4.8% vs 5.0% (P=0.72) |
60 days after cessation of study drug | Efficacy: noninferiority established; superiority established compared to LMWH Safety: no difference in major bleeding between the two treatment groups |
| AMPLIFY24 | 2013 | Multicenter, randomized, double-blind, noninferiority and superiority | Acute VTE | Apixaban 10 mg bid for 7 days followed by 5 mg bid | Enoxaparin 1.0 mg/kg every 12 hours for ≥5 days plus VKA initiated ≤48 hours after randomization | Composite of recurrent symptomatic VTE or VTE-related death: 2.3% vs 2.7% (RR 0.84, 95% CI 0.60–1.18) | Major bleeding: 0.6% vs 1.8% (RR 0.31, 95% CI 0.17–0.55) | 6 months | Efficacy: noninferiority Established Safety: superiority established compared to LMWH |
| AMPLIFY-EXT25 | 2013 | Multicenter, randomized, double-blind, superiority | VTE after 6–12 months of treatment | Apixaban 2.5 mg or 5 mg twice daily | Placebo | Composite of recurrent symptomatic VTE or death from any cause: 3.8% (apixaban 2.5 mg) vs 4.2% (apixaban 5 mg) vs 11.6% (placebo); RR Apixaban 2.5 mg vs placebo: 0.33 (95% CI 0.22–0.48); RR Apixaban 5 mg vs placebo: 0.36 (95% CI 0.25–0.53) | Major bleeding: 0.2% (2.5 mg) vs 0.1% (5 mg) vs 0.5% (placebo); RR Apixaban 2.5 mg vs placebo: 0.49 (95% CI 0.09–2.64); RR Apixaban 5 mg vs placebo: 0.25 (95% CI 0.03–2.24); RR Apixaban 2.5mg vs 5 mg 1.93 (95% CI 0.18–21.25) | 1 year | Efficacy: superiority established compared to placebo for both doses of apixaban Safety: no increased rate of major bleeding |
Abbreviations: THR, total hip replacement; TKR, total knee replacement; VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; RR, relative risk; CI, confidence interval; LMWH, low molecular weight heparin; VKA, vitamin K antagonist; bid, twice daily.