Table 3.
Comparison of the design and main outcomes of the pivotal clinical studies for reduction of stroke risk in NVAF
| Generic name | Dabigatran | Rivaroxaban | Apixaban | Edoxaban | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Study | RE-LY23–25 | ROCKET-AF26 | ARISTOTLE27 | ENGAGE AF-TIMI 4828 | ||||||
| Design | Randomized, open-label for warfarin, blinded for dabigatran | Randomized, double-blind | Randomized, double-blind | Randomized, double-blind | ||||||
| Follow up period, years | 2.0 | 1.9 | 1.8 | 2.8 | ||||||
| Warfarin, TTR, % (mean) | 64 | 55 | 62 | 65 | ||||||
| Dose group | Warfarin | Dabigatran 150 mg | Dabigatran 110 mg | Warfarin | Rivaroxaban | Warfarin | Apixaban | Warfarin | Edoxaban 60 mg | Edoxaban 30 mg |
| Number of patients | 6022 | 6076 | 6015 | 7133 | 7131 | 9081 | 9120 | 7036 | 7035 | 7034 |
| Age, years | 71.6±8.6 (mean ± SD) | 71.5±8.8 (mean ± SD) | 71.4±8.6 (mean ± SD) | 73 (65–78) [median (interquartile range)] | 70 (63–76) [median (interquartile range)] | 72 (64–78) [median (interquartile range)] | ||||
| Male sex, % | 63.3 | 63.2 | 64.3 | 60.3 | 60.3 | 65.0 | 64.5 | 62.5 | 62.1 | 61.2 |
| CHADS2, score (mean±SD) | 2.1±1.1 | 2.2±1.2 | 2.1±1.1 | 3.5±1.0 | 3.5±1.0 | 2.1±1.1 | 2.1±1.1 | 2.8±1.0 | 2.8±1.0 | 2.8±1.0 |
| Event rate, %/year | Event rate, %/year (RR vs Warfarin) | Event rate, %/year (RR vs Warfarin) | Event rate, %/year | Event rate, %/year (HR vs Warfarin) | Event rate, %/year | Event rate, %/year (HR vs Warfarin) | Event rate, %/year | Event rate, %/year (HR vs Warfarin) | Event rate, %/year (HR vs Warfarin) | |
| Stroke/ systemic embolisma | 1.72 | 1.12 (0.65, 0.52–0.81; P for NI and SUP <0.001) | 1.54 (0.89, 0.73–1.09; P for NI <0.001) | 2.4 | 2.1 (0.88, 0.75–1.03; P for NI <0.001, P for SUP =0.12) | 1.60 | 1.27 (0.79, 0.66–0.95; P for NI <0.001, P for SUP =0.01) | 1.80 | 1.57 (0.87, 0.73–1.04; P for NI <0.001, P for SUP =0.08) | 2.04 (1.13, 0.96–1.34; P for NI =0.005, P for SUP =0.10) |
| NNT/year122(95% CI) | – | 182 (118 to 397) | – | – | 367 (−1031 to 161) | – | 303 (169 to 1501) | – | 481 (−2398 to 219) | – |
| Major bleedingb | 3.61 | 3.40 (0.94, 0.82–1.08; P=0.41) | 2.92 (0.80, 0.70–0.93; P=0.003) | 3.4 | 3.6 (1.04, 0.90–1.20; P=0.58) | 3.09 | 2.13 (0.69, 0.60–0.80; P<0.001) | 3.43 | 2.75 (0.80, 0.71–0.91; P<0.001) | 1.61 (0.47, 0.41–0.55; P<0.001) |
| NNT/year122 (95% CI) | – | 475(−427 to 153) | – | – | −1166 (−178 to 256) | – | 120 (85 to 200) | – | 185 (119 to 420) | – |
Notes: aThis efficacy outcome was analyzed in the intention-to-treat population. bThis safety outcome was analyzed in the safety population.
Abbreviations: CHADS2, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke (double weight); HR, hazard ratio; NI, non-inferiority; NNT, number needed to treat; NVAF, non-valvular atrial fibrillation; RR, relative risk; SUP, superiority; TTR, time in therapeutic range.