Year | 2013 | 2016 | 2017 | 2019 | 2019 |
N | 563 | 2124 | 2725 | 4614 | 1506 |
Study design | Multicenter, open-label RCT | Multicenter, open-label RCT | Multicenter, open-label RCT | Multicenter, open-label RCT | Multicenter, open-label RCT |
Study population | PCI | PCI | PCI | ACS with or without PCI or SIHD with PCI | PCI |
Study groups | Warfarin + P2Y12i vs warfarin + DAPT | Rivaroxaban + P2Y12i vs warfarin + DAPT | Dabigatran + P2Y12i vs warfarin + DAPT | Apixaban + P2Y12i vs warfarin + P2Y12i | Edoxaban + P2Y12i vs warfarin + DAPT |
Study duration | 12 months | 12 months | 14 months | 6 months | 12 months |
Primary safety outcome | Any bleeding by year 1 | TIMI major/or minor bleeding or bleeding requiring medical attention | Major or clinical relevant nonmajor bleeding | Major or clinical relevant nonmajor bleeding | Major or clinically relevant nonmajor bleeding |
Result | 19.4% vs 44.4%, HR, 0.36; 95% CI, 0.26-0.50; P<.0001 | 16.8% vs 26.7%, HR, 0.59; 95% CI, 0.47-0.76; P<.001 | 20.2% vs 25.7%; HR, 0.72; 95% CI, 0.58-0.88; P=.002 | 10.5% vs 14.7% HR, 0.69; 95% CI, 0.58-0.81; P<.001 | 17% vs 20%; HR, 0.83; 95%CI, 0.65-1.05; P=.001 |
Secondary efficacy outcome | Death, MI revascularization, stroke, or stent thrombosis | CV mortality, MI, stroke, or stent thrombosis | Thromboembolic events, death, or unplanned revascularization | Death or ischemic event | CV mortality, stroke, systemic embolic event, MI, definite stent thrombosis |
Result | 11.1% vs 17.6%; HR, 0.60; 95% CI, 0.38-0.94; P=.025 | 6.5% vs 6.0%; HR, 1.08; 95% CI, 0.69-1.68; P=.75 | 11.8% vs 12.8%; HR, 0.89; 95% CI, 0.67-1.19; P=.44 | 6.5% vs 7.3%; HR, 0.89; 95% CI, 0.71-1.11; P=NS | 7% vs 6%; HR, 1.06; 95%CI: 0.71-1.69; P=NS |
Study limitations | ▪ Open label ▪ Not powered to assess efficacy outcomes ▪ Difference in any bleeding driven by minor bleeding with unclear clinical significance | ▪ Open label ▪ Not powered to assess efficacy outcomes | ▪ Open label ▪ Not powered to assess efficacy outcomes | ▪ Open label ▪ Not powered to assess efficacy outcomes ▪ Low percentage time in therapeutic range for warfarin | ▪ Open label ▪ Not powered to assess efficacy outcomes |
Clinical bottom line | Warfarin DT had improved safety and efficacy compared with TT | Rivaroxaban DT had improved safety and noninferior efficacy compared with warfarin TT | Dabigatran DT had improved safety and noninferior efficacy compared with warfarin TT | Apixaban DT had improved safety and noninferior efficacy compared with warfarin DT | Edoxaban DT had noninferior safety and noninferior efficacy compared with warfarin DT |