Major Adverse Events in STEMI Patients Treated with Primary Angioplasty Occur More Frequently at U.S. Compared with Non U.S. Sites: Analysis from the HORIZONS AMI Trial

Bruce R. Brodie, Thomas Stuckey, Bernhard Witzenbichler, Giulio Guagliumi, Jan Z. Peruga, Dariusz Dudek, Ran Kornowski, Franz Hartmann, George Dangas, S.Chiu Wong, Helen Parise, Roxana

Mehran, Gregg W. Stone

Background

● The HORIZONS trial trial provided an opportunity to compare outcomes with primary PCI for STEMI at sites in the United States versus at sites outside the United States. This has not been previously evaluated.

● Patients enrolled outside of the United States in Europe, Israel and Argentina (OUS) (n = 2,788) were compared with patients enrolled in the United States (US) (n = 814).

Brodie et al ACC 2008

US(N=814)

OUS(N=2788) p value

Age (years)Age (years) 59.859.8 60.2 NS60.2 NS

Gender (Male)Gender (Male) 74.8%74.8% 77.2% NS77.2% NS

RaceRace

WhiteWhite 84.4%84.4% 96.5% <0.000196.5% <0.0001

BlackBlack 8.1%8.1% 0.2% <0.00010.2% <0.0001

HispanicHispanic 6.2%6.2% 2.4% <0.00012.4% <0.0001

AsianAsian 0.5%0.5% 0.7% NS0.7% NS

Brodie et al ACC 2008

Baseline Demographics

US(N=814)

OUS(N=2788) p value

DiabetesDiabetes 20.8%20.8% 15.2% 0.0002 15.2% 0.0002

HypertensionHypertension 59.1%59.1% 51.8% 0.000351.8% 0.0003

HyperlipidemiaHyperlipidemia 46.8%46.8% 42.0% 0.01442.0% 0.014

Current SmokerCurrent Smoker 43.0%43.0% 47.1% 0.04147.1% 0.041

Prior MIPrior MI 13.8%13.8% 10.1% 0.00310.1% 0.003

Prior CABGPrior CABG 5.5%5.5% 2.2% <0.00012.2% <0.0001

Killip Class 3-4Killip Class 3-4 2.1%2.1% 1.5% NS1.5% NS

BMIBMI 28.028.0 26.8 <0.000126.8 <0.0001

Renal InsufficiencyRenal Insufficiency 4.7%4.7% 2.4% 0.0012.4% 0.001

Brodie et al ACC 2008

Baseline Clinical Variables

US(N=814)

OUS(N=2788) p value

Infarct ArteryInfarct Artery

LADLAD 35.3%35.3% 42.1% 0.000642.1% 0.0006

CFXCFX 15.1%15.1% 16.0% NS16.0% NS

RCARCA 47.1%47.1% 40.6% 0.00140.6% 0.001

SVGSVG 2.1%2.1% 0.6% 0.00030.6% 0.0003

LVEF < 40%LVEF < 40% 20.8%20.8% 12.7% <0.000112.7% <0.0001

TIMI 2-3 Flow InitialTIMI 2-3 Flow Initial 31.1%31.1% 35.6% 0.0235.6% 0.02

Symtom –Door (hrs)Symtom –Door (hrs) 1.81.8 2.3 <0.00012.3 <0.0001

Door-Angio (min)Door-Angio (min) 6767 61 0.000761 0.0007

Brodie et al ACC 2008

Angiographic Variables

OUS

Primary PCI Deferred PCI CABG Medical Rx

89.6% 93.7%

US

Brodie et al ACC 2008

Primary Management Strategy

US(N=814)

OUS(N=2788) p value

Pre-rand Heparin 70.8% 64.0% 0.0003

Clopidogrel Load

300 mg 49.6% 30.8% <0.0001

600 mg 49.7% 67.7% <0.0001

Any IIb/IIIa Inhibitor 55.7% 54.0% NS

Abciximab 43.4% 55.4% 0.002

Eptifibatide 56.6% 43.9% <0.0001

Tirofiban 0% 0.9% 0.049

Bail-out IIb/IIIa Inhib 10.1% 6.8% 0.029

Brodie et al ACC 2008

Adjunctive Pharmacology

Brodie et al ACC 2008

US Better OUS Better

1.47

1.39

1.56

2.5

2.04

0 1 2 3 4

DEATH

MAJOR BLEEDING

MACE

NACE

DEATH/MI

30 Day Outcomes: US vs OUS

● Adjusted Hazard Ratios (95% CI)

STEMI patients enrolled in the HORIZONS-AMI Trial in the US had a much higher risk profile than patients enrolled outside the US.

HORIZONS patients treated with primary PCI in the US had higher rates of death, death/MI, MACE, major bleeding and NACE compared with OUS patients.

After adjusting for differences in baseline variables, US patients had significantly higher rates of MACE, Major Bleeding and NACE compared with OUS patients.

Both US and OUS patients had lower event rates with bivalirudin compared with IIb/IIIa platelet inhibitors. There were no significant interactions between US vs OUS sites and randomization treatment.

Brodie et al ACC 2008

Conclusions