effect of switching antithrombin agents for primary angioplasty in acute myocardial infarction the...

Effect of Switching Antithrombin Agents for Primary Angioplasty in Acute Myocardial Infarction

The HORIZONS-SWITCH Analysis

HORIZONS AMI

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


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).

9.2

6.0 5.8

13.6

5.23.6 4.5

8.7

0

5

10

15

20

Major bleeding(non-CABG)

TIMI majorbleed

MACE NACE

Control (n=1178) Switch to bivalirudin (n=1179)

P=0.0002

P=0.007P=0.0001

30-

day

ev

ent

rate

s (%

)

P=0.18


HORIZONS-AMI Switch 30-day Outcomes

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)

9.96.4

18.6

25.3

6.04.0

17.5

21.4

0

5

10

15

20

25

30

Major bleeding(non-CABG)

TIMI majorbleed

MACE NACE

Control (n=1178)

Switch to bivalirudin (n=1179)

P=0.01

P=0.007P=0.0004

2-y

ear

eve

nt r

ates

(%

) P=0.06


HORIZONS-AMI Switch 2-Year Outcomes

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)

3.8

7.1

11.8 11.9

2.34.0

12.7

7.8

0

5

10

15

20

Cardiac death MI TVR Death /MI

Control (n=1178)

Switch to bivalirudin (n=1179) P=0.001

P=0.002P=0.04

30-d

ay

even

t ra

tes

(%)

P=0.48


HORIZONS-AMI Switch 30-day Outcomes

(Target VesselRevascularization)

3.8

7.1

11.8 11.9

2.34.0

12.7

7.8

0

5

10

15

20

Cardiac death MI TVR Death /MI

Control (n=1178)

Switch to bivalirudin (n=1179) P=0.001

P=0.002P=0.04

2-y

ear

eve

nt r

ates

(%

)

P=0.48


HORIZONS-AMI Switch 2-Year Outcomes

(Target VesselRevascularization)

HORIZONS-AMI Switch 2-Year

0 3 6 9 12 15 18 21 24

0

5

10

15

20

25

30

Net

Adv

erse

Clin

ical

Eve

nts

(%)

Time (months)

Switch to Bivalirudin alone (n=1178)

Control Heparin plus GP IIb/IIIa (n=1179)

25.3%

21.4%

30-day HR [95%CI] = 0.63 [0.49, 0.80]

p <0.001

2-year HR [95%CI] = 0.81 [0.68, 0.96]

p=0.01


Net adverse clinical events = Death/MI/target vessel revascularization, stroke. non-CABG major bleeding.


0 3 6 9 12 15 18 21 24

0

1

2

3

4

5

6

Car

diac

Mor

talit

y (%

)

Time (months)

3.8%

2.3%

30-day HR [95%CI] = 0.56 [0.32, 0.98]

p=0.04

2-year HR [95%CI] = 0.61 [0.38, 0.99]

p=0.04





0 3 6 9 12 15 18 21 24

0

2

4

6

8

10

12

Maj

or B

leed

ing

(%)

Time (months)

13.0%

8.4%

30-day HR [95%CI] = 0.60 [0.46, 0.79]

p <0.001

2-year HR [95%CI] = 0.63 [0.49, 0.81]

p <0.001

14

16





0 3 6 9 12 15 18 21 24

0

1

2

3

4

5

6

Ste

nt T

hrom

bosi

s (%

)

Time (months)

4.3%

3.1%

30-day HR [95%CI] = 1.17 [0.68, 2.02]

p=0.57

2-year HR [95%CI] = 0.73 [0.46, 1.15]

p=0.17




HORIZONS-AMI Switch Group

NACE MACE Major Bleeding(non-CABG-related)

p=0.59

p=0.78 p=0.65


Baseline ACT <200 s (n=637) median 158 s

Baseline ACT ≥200 s (n=362) median 257 s

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)

● 30-day outcomes by ACT at the start of PCI before bivalirudin administration


Mortality,All Cause

Reinfarction Stent Thrombosis

p=0.35 p=0.60 p=0.39


● 30-day outcomes by ACT at the start of PCI before bivalirudin administration



ACT= Activated Clotting Time


NACE MACE Major Bleeding(non-CABG-related)

p=0.36

p=0.76

p=0.32




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)

● 2-year outcomes by ACT at the start of PCI before bivalirudin administration


p=0.80p=0.72

p=0.79

Mortality,All Cause

Reinfarction Stent Thrombosis




ACT= Activated Clotting Time

● 2-year outcomes by ACT at the start of PCI before bivalirudin administration

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


effect of switching antithrombin agents for primary angioplasty in acute myocardial infarction the...

Documents