Table 3.
Efficacy (ITT population) and safety endpoints (on-treatment population) by SVD subtype and for patients with no SVD
| (A) Event rates | |||
|---|---|---|---|
| Outcomes | AS events/100 pt-years (CI) (total events) | MR or AR events/100 pt-years (CI) (total events) | No SVD events/100 pt-years (CI) (total events) |
| Efficacy outcomes | |||
| Stroke or SE | 4.21 (1.89 to 6.53) (17) | 2.01 (1.50 to 2.52) (69) | 2.09 (1.89 to 2.29) (487) |
| Stroke, SE, or vascular death | 10.84 (7.23 to 14.45) (41) | 4.54 (3.78 to 5.30) (152) | 4.31 (4.03 to 4.59) (982) |
| Stroke, SE, vascular death, or MI | 12.09 (8.25 to 15.93) (45) | 5.72 (4.86 to 6.58) (189) | 4.99 (4.68 to 5.30) (1128) |
| Stroke | 3.68 (1.52 to 5.84) (15) | 1.71 (1.24 to 2.18) (59) | 1.96 (1.77 to 2.15) (458) |
| Early study drug discontinuation (%)* | 58.4 (51.5 to 65.1) (125) | 39.6 (37.3 to 41.9) (685) | 34.0 (33.2 to 34.8) (4161) |
| Stroke per-protocol on-treatment* | 4.30 (1.81 to 6.79) (12) | 1.50 (1.04 to 1.96) (39) | 1.90 (1.70 to 2.10) (354) |
| All-cause death | 11.22 (7.65 to 14.79) (43) | 4.90 (4.12 to 5.68) (164) | 4.39 (4.11 to 4.67) (1002) |
| Safety outcomes | |||
| Major or NMCR bleeding | 24.36 (18.14 to 30.58) (59) | 17.66 (15.98 to 19.34) (422) | 14.16 (13.60 to 14.72) (2431) |
| Major bleeding | 7.61 (4.35 to 10.87) (21) | 4.86 (4.03 to 5.69) (131) | 3.27 (3.01 to 3.53) (625) |
| Gastrointestinal bleeding | 2.90 (0.89 to 4.91) (8) | 2.12 (1.57 to 2.67) (57) | 1.32 (1.16 to 1.48) (252) |
| Intracranial haemorrhage | 1.40 (0.03 to 2.77) (4) | 0.76 (0.43 to 1.09) (21) | 0.59 (0.48 to 0.70) (114) |
| (B) Group comparisons | |||
|---|---|---|---|
| Outcomes | AS vs No SVD HR (CI) |
AS vs MR or AR HR (CI) |
MR or AR vs no SVD HR (CI) |
| Efficacy outcomes | |||
| Stroke or SE | 1.82 (1.10 to 3.01)* | 1.87 (1.08 to 3.23)* | 0.97 (0.75 to 1.26) |
| Stroke, SE or vascular death | 2.03 (1.47 to 2.79)** | 2.12 (1.49 to 3.01)** | 0.96 (0.80 to 1.14) |
| Stroke, SE, vascular death or MI | 1.91 (1.41 to 2.59)** | 1.84 (1.32 to 2.56)** | 1.04 (0.88 to 1.21) |
| Stroke | 1.70 (1.00 to 2.92)* | 1.93 (1.07 to 3.46)* | 0.88 (0.67 to 1.16) |
| All-cause death | 1.88 (1.38 to 2.56)** | 1.94 (1.38 to 2.72)** | 0.97 (0.82 to 1.15) |
| Safety outcomes | |||
| Major or NMCR bleeding | 1.28 (0.98 to 1.66) | 1.14 (0.87 to 1.51) | 1.12 (1.00 to 1.24)* |
| Major bleeding | 1.61 (1.03 to 2.49)* | 1.24 (0.78 to 1.97) | 1.30 (1.07 to 1.57)** |
| Gastrointestinal bleeding | 1.39 (0.68 to 2.83) | 1.04 (0.49 to 2.18) | 1.34 (1.00 to 1.80)* |
| Intracranial haemorrhage | 2.04 (0.75 to 5.60) | 1.63 (0.55 to 4.77) | 1.26 (0.79 to 2.01) |
*Although early study drug discontinuation rates were different in the three groups, event rates for stroke were not markedly different between on-treatment and ITT patients.
Event rates are underadjusted.
p Values for group comparisons: *p<0.05, **p<0.01.
AS, aortic stenosis; CI, confidence interval; ITT, intention to treat; MI, myocardial infarction; MR or AR, mitral or aortic regurgitation; NMCR, non-major clinically relevant; pt-years, patient-years; SE, systemic embolism; SVD, significant valve disease.