for the main comparison.
| Factor Xa inhibitors compared with vitamin K antagonists for preventing stroke and other systemic embolic events in patient with atrial fibrillation | ||||||
|
Patient or population: people with atrial fibrillation deemed eligible for long‐term anticoagulant treatment Settings: hospital‐based setting Intervention: factor Xa inhibitor1 Comparison: dose‐adjusted vitamin K antagonist2 | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Warfarin | Factor Xa inhibitors | |||||
|
Stroke and other systemic embolic events Follow‐up: 12 weeks to 2.8 years |
34 per 1000 |
32 per 1000 (33 to 28) |
OR 0.89 (0.82 to 0.97) |
67477 (13) | ⊕⊕⊕⊕ high | Most data (90%) from studies of apixaban, edoxaban and rivaroxaban |
|
All strokes Follow‐up: 12 weeks to 2.8 years |
30 per 1000 |
28 per 1000 (29 to 24) |
OR 0.89 (0.81 to 0.97) |
67449 (13) | ⊕⊕⊕⊕ high | Most data (90%) from studies of apixaban, edoxaban rivaroxaban |
|
Major bleedings Follow‐up: 12 weeks to 2.8 years |
51 per 1000 |
41 per 1000 (43 to 38) |
OR 0.78 (0.73 to 0.84) |
67396 (13) | ⊕⊕⊕⊝ moderate3 | Most data (90%) from studies of apixaban, edoxaban and rivaroxaban |
|
Intracranial haemorrhages Follow‐up: 12 weeks to 2.8 years |
13 per 1000 |
7 per 1000 (8 to 6) |
OR 0.50 (0.42 to 0.59) |
66259 (12) | ⊕⊕⊕⊕ high4 | Most data (90%) from studies of apixaban, edoxaban and rivaroxaban |
|
All‐cause deaths Follow‐up: 12 weeks to 2.8 years |
67 per 1000 |
66 per 1000 (67 to 57) |
OR 0.89 (0.83 to 0.95) |
65624 (10) | ⊕⊕⊕⊝ moderate5 | Most data (90%) from studies of apixaban, edoxaban and rivaroxaban |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; OR: odds ratio. | ||||||
| GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | ||||||
1 The 13 studies included in this review studied the following types of oral and parenteral factor Xa inhibitors: edoxaban, rivaroxaban, apixaban, edoxaban, betrixaban, darexaban, idraparinux and idrabiotaparinux. Assumed risk calculated from pooled data from warfarin treatment arms (mean) of included studies.
2 All included studies used warfarin with a target INR 2.0‐3.0 as active comparator. Three studies performed in Japan had a target INR of 1.6‐2.6 and 2.0‐2.6 in participants aged > 70 years.
3 High, statistically significant heterogeneity was observed in the initial analysis and in pre‐specified sensitivity analysis excluding all open‐label studies (i.e. the prematurely halted AMADEUS trial). Some other heterogeneity might be explained by baseline differences in the included populations in the three largest trials (ROCKET AF, ENGAGE TIMI‐AF and ARISTOTLE). See section Effects of Interventions, Major bleedings for further discussion.
4 High, statistically significant heterogeneity was observed in the initial analysis. No statistically significant heterogeneity was observed in a pre‐specified sensitivity analysis in which data from all open‐label studies were excluded (i.e. prematurely halted AMADEUS trial).
5 Outcome not reported in three trials and was missing/unknown for some randomised participants (up to 2.1% ) in some of the other included trials.