For Internal Use ONLY

AUGUSTUS Trial

Notes, Comments, and Results

For Internal Use ONLY

IMPORTANT NOTES
• THESE SLIDES ARE FOR INTERNAL USE ONLY.
• NOT TO BE DISCLOSED PROACTIVELY!
• TREAT AS CONFIDENTIAL TILL THE FULL
ARTICLE WILL BE PUBLISHED.
• Only the Medical department is allowed to
communicate these results in details.
• THESE RULES HAS NO EXCEPTIONS!
For Internal Use ONLY

Questions to be answered
• The safety of Apixaban vs. VKA in such clinical
situation according to ISTH criteria of
bleeding.
• How (safe/or not safe) is ASA in the treatment
regimens?
 Apixaban
For Internal Use Versus Warfarin in Patients with AF
ONLY
and ACS or PCI: The AUGUSTUS Trial
Inclusion Exclusion

AF (prior, persistent, or >6 hrs Randomize Contraindication to DAPT
duration) n =4,600 Other reason for warfarin

Physician decision that oral Patients (prosthetic valve, mod/sev MS)
anticoag is indicated

ACS and/or PCI with planned
P2Y12 inhibitor for 6 months

Apixaban Warfarin
P2Y12 inhibitor for all patients x 6 months
Aspirin for all on the day of ACS or PCI
Aspirin versus placebo after randomization

ASA placebo ASA placebo

Primary outcome: major/clinically relevant bleeding (through 6 months)

Secondary objective: Death, MI, stroke, stent thrombosis
For Internal Use
ONLY The AUGUSTUS Trial

 A real-world, logistically easy trial, with reduced

SAE reporting, risk based monitoring and minimal
in-person visits, with local labs

 Study Design
 4600 participants,  650 sites,  30 countries
 2x2 factorial design comparing
 Open Label apixaban 5 mg BID vs warfarin (INR 2-3)

Blinded aspirin vs aspirin-placebo
For Internal Use
ONLY
The AUGUSTUS
Trial Study Design
Two Primary Hypotheses (2 x 2 factorial)
Apixaban is non-inferior to warfarin on ISTH major or
clinically relevant non-major bleeding in patients with AF
who develop ACS and/or undergo PCI with planned
antiplatelet therapy.

Single antiplatelet therapy with a P2Y12 inhibitor is

superior to dual antiplatelet therapy with a P2Y12 inhibitor
and aspirin on ISTH major bleeding or clinically relevant
non-major bleeding in patients with AF who develop ACS
and/or undergo PCI with concomitant antiplatelet therapy.
For Internal Use
ONLY The AUGUSTUS Trial
Inclusion / Exclusion Criteria
 Inclusion criteria
 Age >=18 years with atrial fibrillation/flutter with planned
use of oral anticoagulant
 ACS event and/or PCI with stent within past 2 weeks
 Planned P2Y12 inhibitor use for at least 6 months
 Exclusion Criteria
 Serum Cr >2.5 mg/dL or CrCl< 30mL/min
 Other conditions (e.g. DVT or mechanical valves) that
require chronic anticoagulation
 History of intracranial bleeding
 Known bleeding or known contraindications to
anticoagulation
 CABG (planned or completed) for index ACS event
For Internal Use ONLY

ANNONCED IN THE ACC 2019

AUGUSTUS RESULTS
For Internal Use ONLY

Remember the 2*2 Factorial

Apixaban vs VKA

Open-Label

ASA vs Pbo
Blinded
For Internal Use ONLY

31% RRR of Major or CRNM

Bleeding with Apixaban vs VKA

CRNM = Clinical Relevant Non-Major Bleeding

Lopes, et al from AUGUGSTUS investigators. (2019). The New England Journal of Medicine.380(16):1509-1524.
For Internal Use ONLY

Aspirin almost Doubles the Risk of

Major or CRNM Bleeding

CRNM = Clinical Relevant Non-Major Bleeding

Lopes, et al from AUGUGSTUS investigators. (2019). The New England Journal of Medicine.380(16):1509-1524.
For Internal Use ONLY

Apixaban
had the LOWEST event rate

CRNM = Clinically Relevant Non-Major Bleeding

Lopes, et al from AUGUGSTUS investigators. (2019). The New England Journal of Medicine.380(16):1509-1524.
For Internal Use ONLY

Apixaban has a comparable

efficacy to the current SOC

SOC = Standards of Care.

Lopes, et al from AUGUGSTUS investigators. (2019). The New England Journal of Medicine.380(16):1509-1524.
For Internal Use ONLY

Lopes, et al from AUGUGSTUS investigators. (2019). The New England Journal of Medicine.380(16):1509-1524.
For Internal Use ONLY

Comparison of the FOUR scenarios

Safety:
– Apixaban group has 31% RRR of bleeding*
compared with warfarin.
– Placebo group has 47% RRR of bleeding*
compared with those taking aspirin.
– Highest bleeding was in Triple therapy
(VKA+ASA+Clop. = 18.5%)
– Lowest bleeding was in Dual Therapy
(Apixaban+Clop. = 7.3%)
* Both (major or clinically relevant nonmajor bleeding)
For Internal Use ONLY

Comparison of the FOUR scenarios(2)

• Stroke:
– Apixaban group has 50% lower risk compared with
warfarin.
• Death/Hospitalization:
– Highest events rate was in Triple therapy
(VKA+ASA+Clop. = 27.5%)
– Lowest event rate was in Dual Therapy
(Apixaban+Clop. = 22%)
For Internal Use ONLY

Thank You
For Internal Use ONLY
Recommendation to use Clopidogrel with OACs
(While OMMITTING ASA)
ASA
Had (IIb B) recommendation in ACC

January CT et al(2014) J Am Coll Cardiol. 2014 Dec 2;64(21):e1-76 (ACC Guidelines).