Mega JL, Braunwald E, Wiviott SD, et al from ATLAS ACS 2–TIMI 51 Investigators.

Rivaroxaban in patients
with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. doi: 10.1056/NEJMoa1112277.
ATLAS ACS-2, TIMI 51
– Study Design

Group 1 Rivaroxaban 2.5 mg/BID + DAPT

Recent ACS R Group 2 Rivaroxaban 5 mg/BID + DAPT

Group 3 Placebo + DAPT

Mega JL, Braunwald E, Wiviott SD, et al from ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients
with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. doi: 10.1056/NEJMoa1112277.
ATLAS ACS-2, TIMI 51
– Study Design
1ry Endpoints Secondary Endpoints
• Composite of CV mortality, MI, or Composite of all-cause mortality, MI or
stroke (efficacy) stroke
• TIMI major bleeding not associated
with CABG (safety)

Mega JL, Braunwald E, Wiviott SD, et al from ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients
with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. doi: 10.1056/NEJMoa1112277.
ATLAS ACS-2, TIMI 51
– Study Results
Rivaroxaban Pbo
2.5mg 5mg Combined
1ry EndPoints 9.1 8.8 8.9 10.7
CVD 2.7 4 3.3 4.1
MI 6.1 4.9 5.5 6.6
Any Stroke 1.4 1.7 1.6 1.2
IS 1 0.9 0.9 1
2ry Endpoints 9.3 9.1 9.2 11

CVD: Cardiovascular Death; MI: Myocardial

Infarction; IS: Ischemic Stroke; ; Pbo: Placebo.
Mega JL, Braunwald E, Wiviott SD, et al from ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients
with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. doi: 10.1056/NEJMoa1112277.
ATLAS ACS-2, TIMI 51
– Study Results (Safety)
Rivaroxaban Pbo
2.5mg 5mg Combined
TIMI(Non-CABG) 1.8 2.4 2.1 0.6
TIMI Minor 0.9 1.6 1.3 0.5
TIMI (attention) 12.9 16.2 14.5 7.5
ICH 0.4 0.7 0.6 0.2
Fatal 0.1 0.4 0.3 0.2

ICH: Intracranial Hemorrhage; Pbo: Placebo.

Mega JL, Braunwald E, Wiviott SD, et al from ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients
with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. doi: 10.1056/NEJMoa1112277.
ATLAS ACS-2, TIMI 51 NOT SAFE AT ALL!

– Study Results (Safety)

Rivaroxaban Pbo
2.5mg 5mg Combined
TIMI(Non-CABG) 1.8 2.4 2.1 0.6
TIMI Minor 0.9 1.6 1.3 0.5
TIMI (attention) 12.9 16.2 14.5 7.5
ICH 0.4 0.7 0.6 0.2
Fatal 0.1 0.4 0.3 0.2

RRI: Relative Risk Increase; ICH: Intracranial Hemorrhage;

Pbo: Placebo.
Mega JL, Braunwald E, Wiviott SD, et al from ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients
with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. doi: 10.1056/NEJMoa1112277.
ATLAS ACS-2, TIMI 51
– Study Limitations
Published Study 1 Other Sources 2

NONE! FDA declined approval of rivaroxaban

for ACS in May 2012 , citing:
High incomplete follow up (12%)
Vital status missing (9%)
Uncounted deaths
Different rates of outcomes
between first and second halves of
the trial are concerning for
informative censoring

• Generalizability
• Rivaroxaban is not available at lower
dose formulations

1. Mega JL, Braunwald E, Wiviott SD, et al from ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients with a
recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. doi: 10.1056/NEJMoa1112277.
2. https://www.wikijournalclub.org/wiki/ATLAS_ACS-2,_TIMI_51