Outcomes in Elderly Patients Undergoing PCI Treated with Bivalirudin Monotherapy versus Glycoprotein IIb/IIIa Inhibitors with Heparin or LMWH: Results from the Randomized ACUITY Trial - PowerPoint PPT Presentation

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Outcomes in Elderly Patients Undergoing PCI Treated with Bivalirudin Monotherapy versus Glycoprotein IIb/IIIa Inhibitors with Heparin or LMWH: Results from the Randomized ACUITY Trial

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... E. Magnus Ohman, Michel E. Bertrand, Frederic Feit, Charles V. Pollack Jr, ... Elderly patients presenting with NSTE ACS are at high risk for recurrent ... – PowerPoint PPT presentation

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Title: Outcomes in Elderly Patients Undergoing PCI Treated with Bivalirudin Monotherapy versus Glycoprotein IIb/IIIa Inhibitors with Heparin or LMWH: Results from the Randomized ACUITY Trial


1
Outcomes in Elderly Patients Undergoing PCI
Treated with Bivalirudin Monotherapy versus
Glycoprotein IIb/IIIa Inhibitors with Heparin or
LMWH Results from the Randomized ACUITY Trial
  • Karen P. Alexander, E. Magnus Ohman, Michel E.
    Bertrand, Frederic Feit, Charles V. Pollack Jr,
    James Hoekstra, Bernard J. Gersh, Harvey D.
    White, Gregg W. Stone for the ACUITY Investigators

2
Disclosures
  • Research Funding (Minor) Schering Plough, BMS,
    Amgen, CV Therapeutics
  • Speakers Bureau Pfizer

3
Background
  • Elderly patients presenting with NSTE ACS are at
    high risk for recurrent ischemic events
  • Use of antithrombotic therapy and an early
    invasive strategy are beneficial
  • Elderly patients are at high risk for bleeding
    with antithrombotic therapy and catheter
    interventions
  • Major bleeding is associated with adverse
    outcomes
  • Therapy for NSTEACS has become multi-tiered,
    particularly in pts undergoing PCI

4
Bivalirudin
  • Bivalirudin is a direct thrombin inhibitor with
    certain advantages
  • Circulating and clot bound thrombin, no
    requirement for AT III, may reduce thrombin
    mediated platelet activity
  • Clearance by proteolysis, with minor renal
    contribution
  • Short half life, no required monitoring
  • Studied in trials which enrolled PCI pts with
    various comparison groups
  • Similar protection from ischemic events
  • Superior bleeding profile compared to standard
    combination therapy

Replace-2, Protect TIMI 30, ACUITY, BAT
5
ACUITY Trial Moderate-high risk NSTE ACS
undergoing invasive care (13, 819 patients, 448
centers,17 countries)
Exclusion Criteria
Inclusion Criteria
  • No angiography within 72h
  • Acute STEMI or shock
  • Bleeding diathesis or major bleed within 2 weeks
  • Platelet count 100,000/mm3
  • INR gt1.5 control
  • CrCl 30 ml/min
  • Abcx or 2 prior LMWH doses
  • Prior UFH, LMWH (1 dose), eptifibatide and
    tirofiban OK
  • Chest pain 10 within 24h
  • At least one of
  • New ST depression or transient ST elevation 1
    mm
  • Troponin I, T, or CKMB?
  • Documented CAD
  • All other 4 TIMI risk criteria
  • Age 65 years
  • Aspirin within 7 days
  • 2 angina episodes w/i 24h
  • 3 cardiac risk factors

ACUITY Design. Stone GW et al. AHJ 200414876475
6
ACUITY Design Randomization
Moderate-high risk unstable angina or NSTEMI
undergoing an invasive strategy (N 13,819)
UFH or Enoxaparin
Bivalirudin
Moderate- high risk ACS
Routine upstream GPI in all pts
Angiography within 72h
GPI started in CCL for PCI only
Aspirin in all Clopidogrel dosing and timing per
local practice
Bivalirudin Alone
Stratified by pre-angiography thienopyridine use
or administration
ACUITY Design. Stone GW et al. AHJ 200414876475
7
ACUITY Primary Endpoint at 30 days
  • Net Clinical Endpoint
  • Composite ischemic and non-CABG major bleeding
    endpoints
  • Ischemic Endpoint
  • Death, MI, or unplanned revascularization
  • Non-CABG Major Bleeding Endpoint
  • Intracranial, intraocular, or retroperitoneal
    bleeding
  • Access site bleed requiring intervention/surgery
  • Hematoma 5 cm
  • Hgb ?3g/dL with an overt source or ?4g/dL w/o
    overt source
  • Blood transfusion

8
ACUITY Primary Results by Treatment
Heparin GP IIb/IIIa (4603) Bivalirudin GP IIb/IIIa (4604) Bivalirudin GP IIb/IIIa (4604) Bivalirudinalone (4612) Bivalirudinalone (4612)
Endpoint Rate Rate P Value Rate P Value
Net clinical outcome 11.7 11.8 lt0.001 NI 10.1 0.015 Sup
Ischemic events 7.3 7.7 0.007 NI 7.8 0.011 NI
Major bleeding 5.7 5.3 lt0.001 NI 3.0 lt0.001 Sup
NI non-inferiority Sup superiority
Dr. Gregg Stone, ACC 2006 Presentation
9
Purpose
  • To compare age subgroup results with Bivalirudin
    monotherapy, heparin/GPI and Bival/GPI in PCI
    patients in ACUITY
  • Ischemic Endpoints
  • Major and Minor Bleeding
  • Describe differences across age
  • In terms of absolute risk reduction
  • Among those with preserved renal function

10
Baseline Characteristics by Age Subgroups PCI
Cohort n7,789 56
lt55 55-64 65-74 75 N () 2,052 (26.3) 2,240
(28.8) 2,121 (27.2) 1,376 (17.7) Age (yrs) 48.0
4.9 59.6 2.8 69.3 2.9 79.3 3.5 Weight
(kg) 92.1 19.9 88.4 17.7 83.4 16.0 76.4 14.1
Female () 18.4 23.3 29.8 40.6 HTN 50.7 63.4 73.4
77.0 DM 22.0 28.1 30.7 29.4 CVA 2.5 5.0 6.9 9.4
Renal Insuff 2.1 4.5 7.3 11.0 EF
lt30 2.5 3.6 3.4 4.3
Continuous Variables as Means SD
11
Cardiac Markers and Creatinine Clearance PCI
Cohort n7,789 56
lt55 55-64 65-74 75 N () 2,052 (26.2) 2,240
(28.8) 2,121 (27.2) 1,376 (17.7) Hgb
(mg/dl) 14.6 1.5 14.31.5 13.9 1.6 13.4
1.6 Troponin I (gtULN) 65.2 63.9 63.8 62.8 CrCl
(ml/min) 127 62 107 318 79 36 59 36 CrCl
90 () 84.8 60.9 25.8 4.7 CrCl 60-90
() 13.4 33.0 53.0 36.3 CrCl 30-60
() 1.0 5.4 20.6 55.2 CrCl lt30
() 0.8 0.7 0.6 3.7
Continuous Variables as Means SD
12
Combined Ischemic EndpointPCI Cohort by Age
Groups
12.2
12.3
11.0
9.3
9.0
8.6
8.6
8.2
8.3
7.1
7.0
6.5
N2240
N2052
N2121
N1376
Patient Age
P for all comparisons NS
13
Major Bleeding EndpointPCI Cohort
Excluding CABG-related bleeding
14
Implication for Number Needed to Treat (NNT)
Given the Absolute Risk Reduction (ARR) in Major
Bleeding with Bivalirudin vs. Heparin/GPI
40
38
37
16
Patient Age
15
Minor BleedingPCI Cohort




35.5


33.2

28.9
28.6
28.8

24.7
22.5
20.6
19.5
14.3
14.4
12.5
N2240
N2052
N2121
N1376
Patient Age
Plt0.001 Plt0.0001
Excluding CABG-related bleeding
16
Implication for NNT given the ARR in Minor
Bleeding with Bivalirudin vs. Heparin/GPI
Major Bleeding Rate with Heparin/GPI
14
10
8
7
Patient Age
17
Limiting Cohort to CrCl gt50cc/minaddressing the
question of renal dosing
93
92
85.5
62
Patient Age
18
Combined Ischemic Endpoints PCI Cohort with CrCl
gt50 cc/min
12.3
P0.04
10.4
9.6
9.3
8.7
8.5
8.0
8.0
7.8
7.4
6.7
6.6
N2063
N1909
N1813
N849
Patient Age
All other P NS
19
Non-CABG Major Bleeding Endpoint PCI Cohort
with CrCl gt50 cc/min
P0.019
Plt0.001
12.7
9.6
P0.008
0.049
P0.002
P0.021
PNS
6.3
5.9
5.7
P0.012
5.0
4.5
4.1
4.3
3.5
2.8
1.9
N1813
N849
N2063
N1909
Patient Age
Patient Age
20
Implication for NNT Given ARR in Major Bleeding
with Bivalirudin vs. Heparin/GPIPCI Cohort with
CrCl gt50 cc/min
42
45
34
Major Bleeding Rate with Heparin/GPI
20
Patient Age
21
Conclusions
  • Ischemic and hemorrhagic events increase with age
  • Across all age groups, bivalirudin is associated
    with significantly less major and minor bleeding
    and similar ischemic outcomes
  • Even among those with preserved renal function
  • ARR for major bleeding was greatest in the
    elderly (age gt75)
  • NNT of 16 to prevent one major bleed
  • NNT of 8 to prevent one minor bleed
  • Dose all agents carefully, fewer agents may be
    better
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