Presentation at a Non PCI Facility Presentation at a Non PCI Facility Requiring Transfer Does NOT Worsen Requiring Transfer Does NOT Worsen Long-term Prognosis in Patients With Long-term Prognosis in Patients With

STEMI Undergoing Primary STEMI Undergoing Primary Angioplasty.Angioplasty.

The HORIZONS-AMI Trial – One Year The HORIZONS-AMI Trial – One Year ResultsResults

For the HORIZONS AMI InvestigatorsFor the HORIZONS AMI Investigators

Presentation at a Non PCI Facility Presentation at a Non PCI Facility Requiring Transfer Does NOT Worsen Requiring Transfer Does NOT Worsen Long-term Prognosis in Patients With Long-term Prognosis in Patients With

STEMI Undergoing Primary STEMI Undergoing Primary Angioplasty.Angioplasty.

The HORIZONS-AMI Trial – One Year The HORIZONS-AMI Trial – One Year ResultsResults

For the HORIZONS AMI InvestigatorsFor the HORIZONS AMI Investigators

Jochen Wöhrle, , Bruce R. Brodie, Giulio Guagliumi, Bernhard Witzenbichler, Jan Z. Peruga, Dariusz Dudek,

Ran Kornowski, Franz Hartmann, Bernard J. Gersh, Giora Weisz, Helen Parise, Roxana Mehran, Lynn Vandertie,

Louise Gambone, Gregg W. Stone

Disclosures

Jochen Wöhrle None

Bruce R. Brodie None

Giulio Guagliumi Grant support: LightLab, Medtronic Vascular, Boston

Scientific, Research grant: Boston Scientific

Bernhard Witzenbichler None

Jan Z. Peruga None

Dariusz Dudek, None

Ran Kornowski None

Franz Hartmann None

Bernard J. Gersh None

Giora Weisz None

Helen Parise None

Roxana Mehran Grant support, Lecture fees: The Medicines Company

Lynn Vandertie None

Louise Gambone None

Gregg W. Stone Advisory Board: Boston Scientific; Abbott

Background

Primary PCI is the preferred reperfusion strategy in Primary PCI is the preferred reperfusion strategy in patients with ST elevation myocardial infarctionpatients with ST elevation myocardial infarction

Need for transfer of patients to a PCI facility for primary Need for transfer of patients to a PCI facility for primary PCI is associated with a delay in reperfusion due to time PCI is associated with a delay in reperfusion due to time for transfer compared to patients with direct admission to for transfer compared to patients with direct admission to a PCI center.a PCI center.

Long-term clinical outcomes between patients with need Long-term clinical outcomes between patients with need for transfer compared to patients without need for for transfer compared to patients without need for transfer for primary PCI were examined in the large-scale, transfer for primary PCI were examined in the large-scale, multicenter HORIZONS-AMI trial.multicenter HORIZONS-AMI trial.

Pharmacology ArmPharmacology ArmOne year results One year results

Intention to Treat PopulationIntention to Treat Population

UFH + GP IIb/IIIa inhibitorUFH + GP IIb/IIIa inhibitor(abciximab or eptifibatide)(abciximab or eptifibatide)

Bivalirudin monotherapyBivalirudin monotherapy(± provisional GP IIb/IIIa)(± provisional GP IIb/IIIa)

HHarmonizing armonizing OOutcomes with utcomes with RRevascularevascularizizatiationon and and SStents in AMItents in AMI

3602 pts with STEMI with symptom onset ≤12 hours3602 pts with STEMI with symptom onset ≤12 hours

Aspirin, thienopyridineAspirin, thienopyridine R 1:1

Pharmacology ArmPharmacology ArmOne year results One year results

Intention to Treat PopulationIntention to Treat Population

With TransferWith TransferN=988N=988

Without TransferWithout TransferN=2614N=2614

HHarmonizing armonizing OOutcomes with utcomes with RRevascularevascularizizatiationon and and SStents in AMItents in AMI

3602 pts with STEMI with symptom onset ≤12 hours3602 pts with STEMI with symptom onset ≤12 hours

Baseline Characteristics (i)Baseline Characteristics (i)

First presentationFirst presentation Transfer Hosp.Transfer Hosp.(N=988)(N=988)

PCI Hosp.PCI Hosp.(N=2614)(N=2614)

Age (years)Age (years) 60.0 [52.3, 70.2]60.0 [52.3, 70.2] 60.2 [52.4, 69.8]60.2 [52.4, 69.8]

MaleMale 75.6%75.6% 77.0%77.0%

DiabetesDiabetes 14.3%*14.3%* 17.3%17.3%

HypertensionHypertension 52.2%52.2% 53.9%53.9%

HyperlipidemiaHyperlipidemia 38.6%*38.6%* 44.8%44.8%

Current smokingCurrent smoking 46.9%46.9% 45.8%45.8%

Prior MIPrior MI 9.1%*9.1%* 11.6%11.6%

Prior PCIPrior PCI 6.9%*6.9%* 12.2%12.2%

Prior CABGPrior CABG 2.1%2.1% 3.2%3.2%

Weight (kg)Weight (kg) 80 [70, 90]80 [70, 90] 80 [71, 90]80 [71, 90]

* P<0.05* P<0.05

Baseline Characteristics (ii)Baseline Characteristics (ii)

First presentationFirst presentation Transfer Hosp.Transfer Hosp.(N=988)(N=988)

PCI Hosp.PCI Hosp.(N=2614)(N=2614)

Chest pain – ER, minChest pain – ER, min 106 [60, 191]106 [60, 191] 117 [68, 205]117 [68, 205]

Chest pain – SH, minChest pain – SH, min 196 [135-300]**196 [135-300]** 117 [68-205]117 [68-205]

SH – Cath lab, minSH – Cath lab, min 31 [14-55]**31 [14-55]** 52 [33-77]52 [33-77]

Killip class 2-4Killip class 2-4 8.2%8.2% 8.6%8.6%

Target vessel LADTarget vessel LAD 39.9%39.9% 40.9%40.9%

LVEFLVEF 50 [45, 60]50 [45, 60] 50 [42, 60]50 [42, 60]

Femoral a. accessFemoral a. access 90.3%*90.3%* 95.0%95.0%

Venous accessVenous access 7.6%7.6% 9.4%9.4%

Closure deviceClosure device 29.1%29.1% 29.0%29.0%

* P<0.05* P<0.05 ** P<0.0001** P<0.0001 SH=Study hospitalSH=Study hospital

92.9%

5.0%1.9%0.1%

Primary Management Strategy*Primary Management Strategy*

Transfer HospitalN=988

PCI HospitalN=2614

Primary PCI Deferred PCI CABG Medical Rx

*Primary ITT analysis includes all pts regardless of treatment*Primary ITT analysis includes all pts regardless of treatment

92.7%

5.8%1.5%0.0%

Median Time Intervals – PCI Cohort

16.51730108195

161650116

min

min

Door to Balloon: 134 min

Door to Balloon: 87 min

Treatment Delay67 minutes

ReperfusionTime

272 min

205 min

With transferN=988

Without transferN=2614

Symptom onset to first hospital (P=0.03)Symptom onset to study hospital (P<0.0001)Study hospital ER to cath lab arrival (P<0.0001)Cath lab arrival to first angio (P=0.02)First angio to first balloon inflation (P=0.06)

Symptom onset to first hospital (P=0.03)Symptom onset to study hospital (P<0.0001)Study hospital ER to cath lab arrival (P<0.0001)Cath lab arrival to first angio (P=0.02)First angio to first balloon inflation (P=0.06)

TIMI Flow pre and post PCITIMI Flow pre and post PCI

First presentationFirst presentation Transfer Hosp.Transfer Hosp.(N=988)(N=988)

PCI Hosp.PCI Hosp.(N=2614)(N=2614)

TIMI flow pre PCITIMI flow pre PCI

- TIMI 0/1- TIMI 0/1 62.3%*62.3%* 66.5%66.5%

- TIMI 2- TIMI 2 17.1%17.1% 15.5%15.5%

- TIMI 3- TIMI 3 20.6%20.6% 18.0%18.0%

TIMI flow after PCITIMI flow after PCI

- TIMI 0/1- TIMI 0/1 2.1%2.1% 2.5%2.5%

- TIMI 2- TIMI 2 6.4%6.4% 6.0%6.0%

- TIMI 3- TIMI 3 91.6%91.6% 91.5%91.5%

* P<0.05* P<0.05

Study DrugsStudy Drugs

First presentationFirst presentation Transfer Hosp.Transfer Hosp.(N=988)(N=988)

PCI Hosp.PCI Hosp.(N=2614)(N=2614)

UFH pre randomizationUFH pre randomization 73.2%*73.2%* 62.7%62.7%

Antithrombin in CCLAntithrombin in CCL

- UFH- UFH 51.6%51.6% 50.4%50.4%

- Bivalirudin- Bivalirudin 47.5%47.5% 49.3%49.3%

- Peak ACT- Peak ACT 310 [246, 380]310 [246, 380] 307 [250, 388]307 [250, 388]

GP IIb/IIIa anyGP IIb/IIIa any 53.2%53.2% 54.8%54.8%

- Bail-out per protocol**- Bail-out per protocol** 4.8%*4.8%* 8.6%8.6%

- Abciximab- Abciximab 32.3%*32.3%* 27.2%27.2%

- Eptifibatide- Eptifibatide 20.7%*20.7%* 27.3%27.3%

- Tirofiban- Tirofiban 0.3%0.3% 0.4%0.4%** For giant thrombus or refractory no reflow after PCI. ** For giant thrombus or refractory no reflow after PCI. CCL = cardiac catheterization laboratoryCCL = cardiac catheterization laboratory * P<0.01* P<0.01

0

5

10

15

20

Net adverse clinicalevents

Major bleeding* MACE**

One

yea

r eve

nt ra

tes

(%)

Diff = -Diff = -0.4% [-2.8, 1.9] RR = 0.96RR = 0.96 [0.78, 1.20]

P = 0.74P = 0.74

Primary Outcome Measures (ITT)

Diff = 0Diff = 0.5% [-1.5, 2.4] RR = RR = 1.07 [0.82, 1.39]

P = 0.63P = 0.63

Diff = -Diff = -0.9% [-3.6, 1.9]RR = RR = 0.95 [0.79, 1.14]

P = 0.59P = 0.59

*Not related to CABG*Not related to CABG**MACE = All cause death, reinfarction, ischemic TVR or stroke**MACE = All cause death, reinfarction, ischemic TVR or stroke

16.3 17.2

7.9 7.4

11.6 12.0

Transfer Hospital (N=988) PCI Hospital (N=2614)

One Year Net Adverse Clinical EventsOne Year Net Adverse Clinical Events

988 841 817 798 7282614 2216 2155 2111 1896

Number at riskTransferPCI Hospital

Transfer Hospital (n=988)PCI Hospital (n=2614)

NA

CE

(%

)

0

2

4

6

8

10

12

14

16

18

20

22

Time in Months

0 1 2 3 4 5 6 7 8 9 10 11 12

P (interaction) = 0.31

One Year Major Bleeding (non-CABG)One Year Major Bleeding (non-CABG)

988 866 855 841 7662614 2297 2277 2259 2050

Number at riskTransferPCI Hospital

Transfer Hospital (n=988)PCI Hospital (n=2614)

Ma

jor

Ble

ed

ing

(%

)

0

1

2

3

4

5

6

7

8

9

10

11

12

Time in Months

0 1 2 3 4 5 6 7 8 9 10 11 12

P (interaction) = 062

One Year Bleeding EndpointsOne Year Bleeding Endpoints

Transfer Hosp.Transfer Hosp.(N=988)(N=988)

PCI Hosp.PCI Hosp.(N=2614)(N=2614) P ValueP Value

Protocol Major, non CABGProtocol Major, non CABG 7.9%7.9% 7.4%7.4% 0.630.63

Protocol Major, AllProtocol Major, All 10.6%10.6% 9.4%9.4% 0.280.28

Blood transfusionBlood transfusion 3.6%3.6% 3.2%3.2% 0.590.59

TIMI MajorTIMI Major 4.9%4.9% 4.4%4.4% 0.490.49

TIMI MinorTIMI Minor 4.2%4.2% 3.8%3.8% 0.600.60

TIMI Major or MinorTIMI Major or Minor 9.0%9.0% 8.1%8.1% 0.390.39

GUSTO LT* or SevereGUSTO LT* or Severe 0.8%0.8% 0.7%0.7% 0.250.25

GUSTO ModerateGUSTO Moderate 5.3%5.3% 4.2%4.2% 0.160.16

GUSTO LT* or Sev or ModGUSTO LT* or Sev or Mod 5.1%5.1% 4.4%4.4% 0.370.37

*Life threatening*Life threatening

One Year Major Adverse CV EventsOne Year Major Adverse CV Events

988 893 865 843 7682614 2353 2287 2241 2006

Number at riskTransferPCI Hospital

Transfer Hospital (n=988)PCI Hospital (n=2614)

MA

CE

(%

)

0

2

4

6

8

10

12

14

16

Time in Months

0 1 2 3 4 5 6 7 8 9 10 11 12

P (interaction) = 0.41

One Year MACE Components*One Year MACE Components*

First presentationFirst presentation Transfer Hosp.Transfer Hosp.(N=988)(N=988)

PCI Hosp.PCI Hosp.(N=2614)(N=2614) P ValueP Value

DeathDeath 4.0%4.0% 4.2%4.2% 0.800.80

- Cardiac- Cardiac 2.6%2.6% 3.1%3.1% 0.400.40

- Non cardiac- Non cardiac 1.5%1.5% 1.1%1.1% 0.390.39

ReinfarctionReinfarction 4.2%4.2% 3.9%3.9% 0.680.68

- Q-wave- Q-wave 2.1%2.1% 2.1%2.1% 0.930.93

- Non Q-wave- Non Q-wave 2.4%2.4% 1.9%1.9% 0.400.40

Ischemic TVRIschemic TVR 6.0%6.0% 6.7%6.7% 0.420.42

- Ischemic TLR- Ischemic TLR 5.0%5.0% 5.3%5.3% 0.680.68

- Ischemic remote TVR- Ischemic remote TVR 2.3%2.3% 2.1%2.1% 0.790.79

StrokeStroke 1.3%1.3% 1.1%1.1% 0.470.47

*CEC adjudicated*CEC adjudicated

One Year Stent ThrombosisOne Year Stent Thrombosis

Transfer Transfer HospitalHospital(N=850)(N=850)

PCI PCI HospitalHospital(N=2274)(N=2274)

PPValueValue

ARC definite or probable* 2.8%2.8% 3.6%3.6% 0.250.25

- definite 2.6%2.6% 2.9%2.9% 0.580.58

- probable 0.2%0.2% 0.7%0.7% 0.120.12

Late (>30d-1<r), def/prob 1.1%1.1% 1.0%1.0% 0.910.91

*Protocol definition of stent thrombosis, CEC adjudicated*Protocol definition of stent thrombosis, CEC adjudicated

ConclusionsConclusions

In this large scale, international, prospective, In this large scale, international, prospective,

randomized trial of patients with STEMI undergoing a randomized trial of patients with STEMI undergoing a

primary PCI management strategy, despite a median primary PCI management strategy, despite a median

treatment delay of 67 minutes, patients requiring treatment delay of 67 minutes, patients requiring

transfer for PCI compared to those presenting at a PCI transfer for PCI compared to those presenting at a PCI

facility resulted in:facility resulted in:

– Similar one year rates of net adverse clinical eventsSimilar one year rates of net adverse clinical events

– Similar one year rates of major bleedingSimilar one year rates of major bleeding

– Similar one year rates of major adverse Similar one year rates of major adverse

cardiovascular eventscardiovascular events