Table 1.
Subgroup and sensitivity analyses for stroke or systemic embolism and major bleeding relative to standard adjusted dose VKA, OR±95% credible intervals versus standard adjusted dose VKA
| Treatment | Reference case—fixed effect NMA | Subgroup analysis by CHADS2 score |
Subgroup analysis by age |
Subgroup analysis by TTR |
|||
|---|---|---|---|---|---|---|---|
| CHADS2 <2 | CHADS2 ≥2 | Age <75 years | Age ≥75 years | TTR <66% | TTR ≥66% | ||
| Stroke or systemic embolism | |||||||
| Dabigatran 150 mg twice daily | 0.66 (0.53, 0.82) | 0.61 (0.37, 0.999) | 0.66 (0.52, 0.85) | 0.63 (0.46, 0.87) | 0.66 (0.48, 0.90) | 0.54 (0.39, 0.73) | 0.81 (0.58, 1.11) |
| Apixaban 5 mg twice daily | 0.78 (0.65, 0.94) | 0.86 (0.57, 1.28) | 0.78 (0.63, 0.95) | 0.85 (0.67, 1.07) | 0.71 (0.53, 0.95) | 0.79 (0.62, 1.003) | 0.79 (0.60, 1.05) |
| Edoxaban 60 mg daily | 0.87 (0.74, 1.02) | NA | 0.87 (0.74, 1.01) | 0.91 (0.73, 1.14) | 0.83 (0.66, 1.04) | 0.83 (0.65, 1.07) * | 0.91 (0.73, 1.13)* |
| Rivaroxaban 20 mg daily | 0.88 (0.74, 1.04) | NA | 0.88 (0.74, 1.04) | 0.95 (0.75, 1.2) | 0.80 (0.63, 1.03) | 0.81 (0.65, 1.01) | 0.72 (0.47, 1.10) |
| Dabigatran 110 mg twice daily | 0.91 (0.74, 1.12) | 1.00 (0.64, 1.55) | 0.89 (0.71, 1.12) | 0.93 (0.7, 1.24) | 0.88 (0.66, 1.19) | 0.91 (0.69, 1.19) | 0.90 (0.66, 1.24) |
| Edoxaban 30 mg daily | 1.14 (0.98, 1.32) | NA | 1.14 (0.98, 1.32) | 1.16 (0.94, 1.44) | 1.13 (0.91, 1.40) | 1.01 (0.80, 1.28)* | 1.24 (1.01, 1.24)* |
| Medium-dose ASA (>100 mg and ≤300 mg daily) | 1.35 (0.74, 2.47) | 1.97 (0.63, 6.73)† | NA | NA | NA | NA | NA |
| Low-dose ASA (≤100 mg daily) | 1.87 (1.26, 2.8) | 2.20 (1.18, 4.25) | 2.10 (0.91, 5.15) ‡ | NA | 2.04 (1.33, 3.20) | NA | NA |
| Clopidogrel 75 mg daily and Low-dose aspirin (≤100 mg daily) | 1.93 (1.42, 2.64) | 3.16 (1.39, 8.22) | 1.15 (0.84, 1.57) | NA | NA | 1.52 (0.96, 2.45) | 2.40 (1.59, 3.71) |
| Major bleeding | |||||||
| Edoxaban 30 mg daily | 0.46 (0.4, 0.54) | NA | 0.46 (0.4, 0.54) | 0.50 (0.41, 0.61)§ | 0.51 (0.41–0.62)§ | 0.45 (0.35, 0.58)*§ | 0.51 (0.43, 0.61)*§ |
| Apixaban 5 mg twice daily | 0.69 (0.6, 0.80) | 0.59 (0.44, 0.78) | 0.73 (0.62, 0.87) | 0.73 (0.6, 0.89) | 0.65 (0.52, 0.80) | 0.57 (0.45, 0.71) | 0.81 (0.67, 0.98) |
| Edoxaban 60 mg daily | 0.79 (0.69, 0.9) | NA | 0.79 (0.69, 0.90) | 0.74 (0.62–0.90)§ | 0.82 (0.68–0.98)§ | 0.69 (0.55, 0.87) ast;§ | 0.83 (0.70, 0.97)*§ |
| Dabigatran 110 mg twice daily | 0.80 (0.69, 0.93) | 0.65 (0.47, 0.89) | 0.86 (0.73, 1.02) | 0.62 (0.49, 0.77) | 1.02 (0.84, 1.25) | 0.74 (0.61, 0.91) | 0.86 (0.69, 1.06) |
| Dabigatran 150 mg twice daily | 0.93 (0.81, 1.08) | 0.77 (0.57, 1.04) | 1.01 (0.86, 1.19) | 0.70 (0.56, 0.86) | 1.19 (0.98, 1.45) | 0.76 (0.62, 0.94) | 1.15 (0.94, 1.40) |
| Rivaroxaban 20 mg daily | 1.03 (0.89, 1.19) | NA | 1.03 (0.89, 1.19) | 0.93 (0.76, 1.13) | 1.15 (0.93, 1.41) | 0.92 (0.77, 1.10) | 1.30 (1.01, 1.69) |
| Low-dose ASA (≤100 mg daily) | 1.05 (0.6, 1.87) | 0.83 (0.42, 1.64) | 1.60 (0.55, 5.02) ‡ | NA | 1.01 (0.57, 1.78) | NA | NA |
| Clopidogrel 75 mg daily and low-dose aspirin (≤100 mg daily) | 1.10 (0.83, 1.47) | 1.51 (0.89, 2.61) | 0.97 (0.69, 1.36)¶ | NA | NA | 0.66 (0.42, 1.02) | 1.66 (1.12, 2.47) |
| Medium-dose ASA (>100 mg and ≤300 mg daily) | 1.79 (0.63, 5.67) | 1.48 (0.11, 19.07)† | NA | NA | NA | NA | NA |
Significant results are in bold.
*Data provided from ENGAGE AF-TIMI 4820 use TTR >60%.
†Results may be slightly biased against medium-dose ASA. Based on study level results from CAFA and JAST studies. Although these studies consisted primarily of low-risk populations, some patients may have CHADS2 scores greater than 2.
‡Results may be slightly biased against LDASA. Derived from the BAFTA study where CHADS2 subgroup data were stratified by CHADS2 1–2 (vs 0–1) and CHADS2 3–6 (vs 2–6).
§Based on overall time period where overall time period was defined as first dose to the last dose plus 3 days.
¶Estimated from the subgroup study by Healey et al (2008).29a
ASA, acetylsalicylic acid; NA, not available; NMA, network meta-analysis; TTR, time in therapeutic range; VKA, vitamin K antagonist.