Gregg W. Stone MD

1
A Prospective, Randomized Trial of Bivalirudin in
Acute Coronary SyndromesFinal One-Year Results
from the ACUITY Trial

• Gregg W. Stone MD
• for the ACUITY Investigators

2
Study Design First Randomization
Moderate and high risk unstable angina or NSTEMI
undergoing an invasive strategy (N 13,819)
33
Moderate and high risk ACS (n13,819)
56
Aspirin in all Clopidogrel dosing and timing per
local practice
11
Stratified by pre-angiography thienopyridine use
or administration
3
Study Design Second Randomization
Moderate and high risk unstable angina or NSTEMI
undergoing an invasive strategy (N 13,819)
Moderate and high risk ACS (n13,819
Aspirin in all Clopidogrel dosing and timing per
local practice
Stratified by pre-angiography thienopyridine use
or administration
4
Ischemic Composite Endpoint(Death, MI, unplanned
revascularization for ischemia)
UFH/Enoxaparin GPI vs. Bivalirudin GPI vs.
Bivalirudin Alone
25
20
15
Ischemic Composite ()
10
HGPI vs. BivalirudinGPI HR 95 CI 1.05
(0.94-1.16)
5
HGPI vs. Bivalirudin alone HR 95 CI 1.05
(0.95-1.17)
0
0
30
60
90
120
150
180
210
240
270
300
330
360
390
Days from Randomization
5
Myocardial Infarction
UFH/Enoxaparin GPI vs. Bivalirudin GPI vs.
Bivalirudin Alone
15
10
MI ()
5
0
0
30
60
90
120
150
180
210
240
270
300
330
360
390
Days from Randomization
6
Unplanned Revascularization
UFH/Enoxaparin GPI vs. Bivalirudin GPI vs.
Bivalirudin Alone
15
10
Unplanned Revasc. ()
5
0
0
30
60
90
120
150
180
210
240
270
300
330
360
390
Days from Randomization
7
Stent Thrombosis (Protocol Defn.)
Drug-eluting Stent (DES) vs. Bare Metal Stent(BMS)
5
P (log rank)
1 year
Estimate
4
0.38
DES (N4630)
2.2
3
Stent Thrombosis ()
2
1
0
0
30
60
90
120
150
180
210
240
270
300
330
360
390
Days from Randomization
8
Mortality 524 total deaths at 1-year
UFH/Enoxaparin GPI vs. Bivalirudin GPI vs.
Bivalirudin Alone
5
HGPI vs. BivalirudinGPI HR 95 CI 0.99
(0.80-1.21)
4
HGPI vs. Bivalirudin alone HR 95 CI 0.95
(0.78-1.18)
3
Mortality ()
2
1
0
0
30
60
90
120
150
180
210
240
270
300
330
360
390
Days from Randomization
9
Death at 1-Year
UFH/Enoxaparin GPIIb/IIIa vs. Bivalirudin alone
1 yr KM estimate
UFH/Enox IIb/IIIa
Hazard ratio 95 CI
Bival alone
HR (95 CI)
Pint
Biomarkers (CK/Trop) Elevated (n5072) Normal
(n3402)
0.40
Pre Thienopyridine Yes (n5751) No (n3305)
0.52
Actual Treatment PCI (n5179) CABG
(n1040) Medical (n2994)
0.96
Bivalirudin alone better
UFH/Enox IIb/IIIa better
10
Impact of MI and Major Bleeding (non-CABG) in the
First 30 Days on Risk of Death Over 1 Year
1 yearEstimate
30
25
20
Mortality ()
15
10
5
0
0
30
60
90
120
150
180
210
240
270
300
330
360
390
Days from Randomization
11
Influence of Major Bleeding and MI in the First
30 Days on Risk of Death Over 1 Year

• Cox model adjusted for baseline predictors, with
  non-CABG major bleeding and MI as time-updated
  covariates

HR 95 CI
P-value
HR (95 CI)
Major bleeding 2.89 (2.24-3.72) lt0.0001
Myocardial Infarction 2.47 (1.87-3.27) lt0.0001
12
Conclusions

• In patients with moderate and high risk ACS
  undergoing an early invasive strategy
  with the use of GP IIb/IIIa
  inhibitors
• Bivalirudin is an acceptable substitute for
  either unfractionated heparin or enoxaparin
• Compared to either UFH/enoxaparin with GP
  IIb/IIIa inhibitors or bivalirudin with GP
  IIb/IIIa inhibitors
• A bivalirudin alone strategy results in marked
  reduction of bleeding at 30 days, and similar
  rates of mortality and composite ischemia at
  1-year
• The results of this study further establish the
  important relationship between iatrogenic
  bleeding complications and the long-term
  prognosis in patients with ACS