Transcript HORIZONS AMI Effect of Switching Antithrombin Agents for Primary Angioplasty in Acute Myocardial Infarction The HORIZONS-SWITCH Analysis Dangas G, et al JACC 2011;57:2309–16

HORIZONS AMI
Effect of Switching Antithrombin Agents for Primary
Angioplasty in Acute Myocardial Infarction
The HORIZONS-SWITCH Analysis
Dangas G, et al JACC 2011;57:2309–16
Background and Methods
● The safety and efficacy of switching anticoagulants in the early
treatment of STEMI is unknown.
● In the HORIZONS-AMI randomized trial, 65.4% of patients in
HORIZONS -AMI received pre-randomization heparin
● The subgroup of HORIZONS-AMI patients (n=2357) treated with
heparin before randomization was analyzed according to
subsequent assignment to bivalirudin (Switch group, n=1178) or to
heparin plus GPI (Control group, n=1179).
● Randomization was stratified according to pre-randomization UFH
administration, therefore the present analysis reflects a stand-alone
randomized comparison less subject to confounding than a
nonrandomized subgroup analysis
Dangas G, et al JACC 2011;57:2309–16
Results
● Patients received heparin in a transfer facility (n=650), ambulance
(n=876), the enrolling hospital (n=797), or multiple locations (n=37).
● Most patients (n=1934) received a UFH bolus only, the rest
received a bolus plus infusion (n=399) or infusion only (n=22).
● The mean UFH bolus dose was 4,912 ±1,684 IU and 4,892 ± 883
IU in the switch versus control groups (p =0.72)
● Study antithrombin was given in the cath lab to 85% of patients,
and in the ED to15% of patients
● The duration from pre-randomization UFH bolus to study drug
initiation was 64 ± 61 min vs 59 ± 55 min in the switch vs control
groups (p=0.05).
● The mean baseline activated clotting time (ACT) levels were 205 ±
95 s vs 183 ± 85 s in the switch versus control groups (p<0.001).
Dangas G, et al JACC 2011;57:2309–16
HORIZONS-AMI Switch
30-day Outcomes
Control (n=1178)
30-day event rates (%)
20
Switch to bivalirudin (n=1179)
P=0.0002
13.6
15
P=0.0001
10
P=0.007
9.2
P=0.18
8.7
5.2
5
6.0
5.8
3.6
4.5
0
Major bleeding
(non-CABG)
TIMI major
bleed
MACE
NACE
MACE= Major Adverse Cardiovascular Events (death, reinfarction, target vessel revascularization for ischemia, or stroke),
NACE= Net Adverse Clinical Events (MACE plus non-CABG major bleeding)
Dangas G, et al JACC 2011;57:2309–16
HORIZONS-AMI Switch
2-Year Outcomes
2-year event rates (%)
30
25
P=0.01
Control (n=1178)
Switch to bivalirudin (n=1179)
10
25.3
21.4
18.6 17.5
20
15
P=0.06
P=0.0004
9.9
6.0
5
P=0.007
6.4
4.0
0
Major bleeding
(non-CABG)
TIMI major
bleed
MACE
NACE
MACE= Major Adverse Cardiovascular Events (death, reinfarction, target vessel revascularization for ischemia, or stroke),
NACE= Net Adverse Clinical Events (MACE plus non-CABG major bleeding)
Dangas G, et al JACC 2011;57:2309–16
30-day event rates (%)
HORIZONS-AMI Switch
30-day Outcomes
Control (n=1178)
20
P=0.48
Switch to bivalirudin (n=1179)
15
11.8
10
P=0.04
12.7
3.8
11.9
P=0.002
7.8
7.1
5
P=0.001
4.0
2.3
0
Cardiac death
MI
TVR
(Target Vessel
Revascularization)
Dangas G, et al JACC 2011;57:2309–16
Death /MI
2-year event rates (%)
HORIZONS-AMI Switch
2-Year Outcomes
Control (n=1178)
20
P=0.48
Switch to bivalirudin (n=1179)
15
11.8
10
P=0.04
12.7
3.8
11.9
P=0.002
7.8
7.1
5
P=0.001
4.0
2.3
0
Cardiac death
MI
TVR
(Target Vessel
Revascularization)
Dangas G, et al JACC 2011;57:2309–16
Death /MI
HORIZONS-AMI Switch 2-Year
Control Heparin plus GP IIb/IIIa (n=1179)
Net Adverse Clinical Events (%)
30
Switch to Bivalirudin alone (n=1178)
25.3%
25
21.4%
20
15
10
30-day HR [95%CI] =
0.63 [0.49, 0.80]
p <0.001
5
2-year HR [95%CI] =
0.81 [0.68, 0.96]
p=0.01
0
0
3
6
9
12
15
Time (months)
18
Net adverse clinical events = Death/MI/target vessel revascularization, stroke. non-CABG major bleeding.
Dangas G, et al JACC 2011;57:2309–16
21
24
HORIZONS-AMI Switch 2-Year
Control Heparin plus GP IIb/IIIa (n=1179)
6
Switch to Bivalirudin alone (n=1178)
Cardiac Mortality (%)
5
4
3.8%
3
2.3%
2
30-day HR [95%CI] =
0.56 [0.32, 0.98]
p=0.04
1
2-year HR [95%CI] =
0.61 [0.38, 0.99]
p=0.04
0
0
3
Dangas G, et al JACC 2011;57:2309–16
6
9
12
15
Time (months)
18
21
24
HORIZONS-AMI Switch 2-Year
Control Heparin plus GP IIb/IIIa (n=1179)
16
Switch to Bivalirudin alone (n=1178)
14
Major Bleeding (%)
13.0%
12
10
8.4%
8
6
4
30-day HR [95%CI] =
0.60 [0.46, 0.79]
p <0.001
2
2-year HR [95%CI] =
0.63 [0.49, 0.81]
p <0.001
0
0
3
Dangas G, et al JACC 2011;57:2309–16
6
9
12
15
Time (months)
18
21
24
HORIZONS-AMI Switch 2-Year
Control Heparin plus GP IIb/IIIa (n=1179)
6
Switch to Bivalirudin alone (n=1178)
Stent Thrombosis (%)
5
4.3%
4
3.1%
3
2
30-day HR [95%CI] =
1.17 [0.68, 2.02]
p=0.57
1
2-year HR [95%CI] =
0.73 [0.46, 1.15]
p=0.17
0
0
3
Dangas G, et al JACC 2011;57:2309–16
6
9
12
15
Time (months)
18
21
24
HORIZONS-AMI Switch Group
● 30-day outcomes by ACT at the start of PCI before bivalirudin administration
Baseline ACT <200 s (n=637) median 158 s
p=0.59
Baseline ACT ≥200 s (n=362) median 257 s
p=0.78
NACE
MACE
p=0.65
Major Bleeding
(non-CABG-related)
ACT= Activated Clotting Time; MACE= Major Adverse Cardiovascular Events (death, reinfarction, target vessel
revascularization for ischemia, or stroke), NACE= Net Adverse Clinical Events (MACE plus non-CABG major bleeding)
Dangas G, et al JACC 2011;57:2309–16
HORIZONS-AMI Switch Group
● 30-day outcomes by ACT at the start of PCI before bivalirudin administration
Baseline ACT <200 s (n=637) median 158 s
Baseline ACT ≥200 s (n=362) median 257 s
p=0.35
Mortality,
All Cause
ACT= Activated Clotting Time
Dangas G, et al JACC 2011;57:2309–16
p=0.60
Reinfarction
p=0.39
Stent Thrombosis
HORIZONS-AMI Switch Group
● 2-year outcomes by ACT at the start of PCI before bivalirudin administration
Baseline ACT <200 s (n=637) median 158 s
p=0.36
Baseline ACT ≥200 s (n=362) median 257 s
p=0.76
p=0.32
NACE
MACE
Major Bleeding
(non-CABG-related)
ACT= Activated Clotting Time; MACE= Major Adverse Cardiovascular Events (death, reinfarction, target vessel
revascularization for ischemia, or stroke), NACE= Net Adverse Clinical Events (MACE plus non-CABG major bleeding)
Dangas G, et al JACC 2011;57:2309–16
HORIZONS-AMI Switch Group
● 2-year outcomes by ACT at the start of PCI before bivalirudin administration
Baseline ACT <200 s (n=637) median 158 s
p=0.80
Baseline ACT ≥200 s (n=362) median 257 s
p=0.72
p=0.79
Mortality,
All Cause
ACT= Activated Clotting Time
Dangas G, et al JACC 2011;57:2309–16
Reinfarction
Stent Thrombosis
Limitations
● Despite the randomized treatment assignment, this substudy of
the HORIZONS-AMI trial should be considered exploratory and
hypothesis-generating due to limited statistical power.
● A switch strategy from UFH to bivalirudin vs continuing UFH
without a GPI was not tested.
● However, previous studies showed that adding a GPI to UFH
reduces mortality and reinfarction after primary PCI, and thus
before the HORIZONS-AMI trial, 90% of patients with STEMI
undergoing primary PCI were treated with UFH plus GPI.
Conclusions
● STEMI patients who receive early treatment with UFH
may be safely switched to bivalirudin, a strategy that
results in reduced hemorrhagic complications and
cardiac mortality and enhanced event-free survival
compared with UFH continuation and initiation of a GPI
Dangas G, et al JACC 2011;57:2309–16