EFFICACY AND SAFETY OUTCOMES IN 8040 WOMEN COMPARED WITH 13085 MEN WITH ATRIAL FIBRILLATION TREATED WITH EDOXABAN VS WARFARIN FOR AN AVERAGE 2.8 YEARS
R.P. Giugliano, M.L. O'Donoghue, C.T. Ruff, P. Merlini, F. Nordio, L.T. Grip, V. Curt, H. Lanz, M. Mercuri, E. Braunwald
1. Brigham and Women's Hospital, Boston; 2. Cardiothoracic Department, Ospedale Niguarda Ca' Granda, Milan, Italy; 3. Daiichi Sankyo Pharma Development, Edison, USA
Background: Women with most cardiac conditions, including atrial fibrillation (AF) are at higher risk for treatment failures and complications.
Methods: We compared outcomes by sex in the ENGAGE AF-TIMI 48 trial, which randomized 21,105 patients to edoxaban or warfarin. The primary endpoint was the composite of all strokes or systemic embolism while the principal safety endpoint was the ISTH-defined major bleeding. Results shown are for the high-dose edoxaban regimen versus warfarin while on-treatment.
Results: Women (n=8040) tended to be older, lighter, had poorer renal function, and higher CHA2DS2VASc scores (each p < 0.001). Edoxaban, as compared to warfarin, tended to reduce stroke or systemic embolism, and significantly reduced major bleeding, to a similar degree in men versus women (Table). Edoxaban reduced hemorrhagic stroke and several secondary bleeding endpoints to an even greater degree in women as compared to men (Table).
Conclusions: Although women were at higher risk for thromboembolic events than men, the efficacy profile of edoxaban is similar in women and men. The safety profile of edoxaban vs. warfarin was enhanced in women, making edoxaban an especially attractive anticoagulant in women.
Results of the Primary Efficacy (stroke or systemic embolism) and Principal Safety (ISTH major bleeding) are shown in italics
* Analyses performed in the overall time period to permit capture of deaths on or off study drug
† Myocardial infarction, stroke, systemic embolic event, or cardiovascular death
‡ Clinically relevant non-major bleeding per ISTH criteria
¶ Composite of death, stroke, systemic embolic event, or major bleeding
| Endpoint |
Warfarin |
HD Edox |
HR (95% CI) |
P-int |
| Stroke/systemic embolism (SE)
Men
Women
|
1.46%
1.55%
|
1.16%
1.21%
|
0.80 (0.62, 1.02)
0.78 (0.57, 1.07)
| 0.91 |
| CV death/stroke/SE*
Men
Women
|
4.60%
4.15%
|
3.99%
3.61%
|
0.87 (0.77, 0.98)
0.86 (0.73, 1.02)
| 0.95 |
| Ischemic stroke
Men
Women
|
1.15%
1.41%
|
1.08%
1.53%
|
0.94 (0.73, 1.19)
1.08 (0.82, 1.42)
| 0.44 |
| Hemorrhagic stroke
Men
Women
|
0.46%
0.50%
|
0.32%
0.15%
|
0.70 (0.46, 1.06)
0.30 (0.15, 0.59)
| 0.037 |
| MACE*†
Men
Women
|
5.18%
4.66%
|
4.57%
4.15%
|
0.88 (0.79, 0.99)
0.89 (0.76, 1.04)
| 0.99 |
| Major Bleeding
Men
Women
|
3.47%
3.35%
|
2.90%
2.48%
|
0.84 (0.72., 0.98)
0.74 (0.59, 0.92)
| 0.34 |
| Intracranial hemorrhage
Men
Women
|
0.82%
0.89%
|
0.51%
0.18%
|
0.63 (0.44, 0.89)
0.20 (0.10, 0.39)
| 0.003 |
| Life-threatening Bleeding
Men
Women
|
0.70%
0.93%
|
0.53%
0.16%
|
0.77 (0.54, 1.10)
0.17 (0.09, 1.35)
| <0.001 |
| Major or CRNM‡ Bleeding
Men
Women
|
12.7%
13.6%
|
11.6%
10.3%
|
0.92 (0.84, 1.00)
0.76 (0.68, 0.85)
| 0.011 |
| 1st Net Clinical Outcome¶
Men
Women
|
8.46%
7.54%
|
7.56%
6.76%
|
0.89 (0.81, 0.98)
0.89 (0.79, 1.01)
| 0.99 |
