Pharmaco-Invasive Approach for STEMI

Michael C. Kontos, MD

Medical Director, Coronary Intensive Care Unit

Director, Chest Pain Evaluation Center

Associate Professor

Departments of Internal Medicine (Cardiology), Radiology and

Emergency Medicine

Virginia Commonwealth University Medical Center

Richmond, Virginia

Disclosures

• Consultant:

• Roche

Primary PCI vs Thrombolysis in STEMI: Quantitative Analysis (23 RCTs, N=7739)

Keeley EC, et al. Lancet. 2003;361:13-20

Treatment Strategies for Patients with Who Require Transfer for Primary PCI

• Primary PCI (no matter how long it takes)

• Full dose fibrinolytics with elective transfer or for rescue PCI

• Full dose fibrinolytics with routine transfer and rescue PCI as needed

• Half dose fibrinolytics with transfer and rescue PCI as needed

30 Day Mortality for Transfer for Primary PCI vs

Immediate Thrombolysis

Giuseppe De Luca et al Ann of Emer Med 2008;52;665–676

23% decrease (p=0.02)

58% decrease in re-MI

Advantage of PCI Compared With Fibrinolysis

Decreases as PCI-Related Delay Increases

Pinto DS, et al. Circulation. 2006;114:2019-2025.

Od

ds o

f D

eath

Wit

h F

ibri

no

lysis

PCI-Related Delay (door-to-balloon–door-to-needle time), min

PC

I B

ett

er

Fib

rin

oly

sis

Bett

er

2.0

1.5

1.25

1.0

0.8

0.5

60 75 90 105 114 135 150 165 180

STEMI Door-to-Balloon Times For Transfer Patients Remain Prolonged

Transfer in DTB Times Non-Transfer in DTB Times

Tim

e (

min

)

ACTION Registry-GWTG DATA: January 01, 2014 - December 31, 2014

25th %tile median

Facilitated PCI

• A strategy to enhance primary PCI by improved early infarct vessel patency

• Options: • full dose thrombolytics

• half dose thrombolytics with GP IIb/IIIa inhibitors

• GP IIb/IIIa inhibitors alone

• No benefit and/or worse outcomes • ASSENT-IV trial--TNK

• FINESSE trial—TNK +/- abciximab

• Limitations: minimal delay to PCI, no routine ADP antagonist used

Pharmaco-Invasive PCI

• A strategy to improve fibrinolysis outcomes for patients where transfer for primary PCI cannot be achieved in recommended times

• Fibrinolytics administered per current guidelines

• Immediate transfer to PCI centers

• PCI of the infarct related artery subsequently performed

45% decrease re-MI

35% decrease D/MI

April 11, 2013

no lytic

Study Protocol 1892 patients randomized

RANDOMIZATION 1:1 by IVRS, OPEN LABEL

Am

bu

lan

ce

/ER

Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to

day 30

ECG at 90 min: ST resolution ≥ 50%

Standard primary PCI

Aspirin

Clopidogrel:

LD 300 mg + 75 mg QD

Enoxaparin:

30 mg IV + 1 mg/kg SC

Q12h

Antiplatelet and

antithrombin treatment

according to local

standards

angio >6 to 24 hrs

PCI/CABG if indicated

immediate angio +

rescue PCI if

indicated

YE

S

N

O

Strategy A: pharmaco-invasive Strategy B: primary PCI

Aspirin

Clopidogrel:

75 mg QD

Enoxaparin:

0.75 mg/kg SC Q12h

PC

I H

osp

ital

STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in

2 leads

≥75y: ½ dose TNK <75y:full dose After 20% of the planned

recruitment, the TNK

dose was reduced by

50% among patients ≥75

years of age.

62

Sx onset

1st Medical

contact

61

1 Hour 2 Hours n=1892

29

Randomize

IVRS

9

Rx TNK

31 86

Sx onset

Rx

PPCI

100

min

178

min

Median Times to Treatment (min)

1st Medical

contact

78 min

difference Randomize

IVRS

117 min D2B Time

62

Sx onset

61

1 Hour 2 Hours

29 9

Rx TNK

31 86

Sx onset

Rx

PPCI

100 min

178 min

Median Times to Treatment (min)

36% Rescue PCI at 2.2h

n=1892

64% non-urgent cath at 17h

1st Medical

contact Randomize

IVRS

1st Medical

contact Randomize

IVRS

117 min D2B Time

PRIMARY ENDPOINT

TNK 12.4%

PPCI 14.3%

TNK vs PPCI

Relative Risk 0.86, 95%CI (0.68-1.09)

p=0.24

Dth

/Sh

ock

/CH

F/R

eMI

(%)

a

30 Day End-Points

Pharmaco-invasive

(N=944)

PPCI

(N=948)

P-value

All cause death

Cardiac death

(43/939) 4.6%

(31/939) 3.3%

(42/946) 4.4%

(32/946) 3.4%

0.88

0.92

Congestive heart

failure

(57/939) 6.1% (72/943) 7.6% 0.18

Cardiogenic shock (41/939) 4.4% (56/944) 5.9% 0.13

Reinfarction (23/938) 2.5% (21/944) 2.2% 0.74

Association of PCI-Related Delay and Treatment

STREAM Sub-Study

Gershlick AH et al. Heart 2015;101:692

30-day death/CHF/MI/shock

Mortality with Pharmaco-Invasive vs Primary PCI Observational Studies

4,3

2,5

4,4

3

5,4

4,4 4,1

7

0

1

2

3

4

5

6

7

8

Ottawa Minneapolis Korea Mayo

Pharmaco-Invasive Primary PCI Primary PCI

Unanswered Questions

• What does of fibrinolytics should be used?

• Full dose? 1/2 dose?

• Is there a benefit of using newer P2Y12 antagonists?

• ticagrelor, prasugrel

• When is the ideal time to perform angiography?

• Immediately? Delayed?

No Harm For Early PCI After Fibrinolytics Patient Level Data From 7 Pharmaco-Invasive Trials

Maden M, et al JACC Interv 2015;8;166

No Harm For Early PCI After Fibrinolytics Patient level Data 7 Trials

Maden M, et al JACC Interv 2015;8;166

Conclusions

• Primary PCI remains the optimal reperfusion therapy when

performed within guideline recommended times

• A pharmaco-invasive strategy in patients in whom primary

PCI is delayed is effective with similar (if not better)

outcomes compared to primary PCI

• Angiography with intent to carry out revascularization after

fibrinolytic treatment should be routinely performed

• Reduced dose fibrinolytics may be considered in older

patients

Gracias!

Virginia Commonwealth University Medical Center (Medical College of Virginia)

Founded 1838

Richmond, Virginia

Original Hospital

From: Early routine percutaneous coronary intervention after fibrinolysis vs. standard therapy in ST-segment

elevation myocardial infarction: a meta-analysis Eur Heart J. 2010;31(17):2156-2169. doi:10.1093/eurheartj/ehq204

Eur Heart J | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010. For permissions

please email: journals.permissions@oxfordjournals.org

Non-PCI Hospitals

Guideline for STEMI

ESC Recommendations

Arch Intern Med. 2011;171(21):1879-1886.

Median door-in to door-out (DIDO) times, 2009

CMS Data, 1034 hospitals, 13,776 patients

Median time 68 (52-91) minutes

9.7% < 30 minutes

31% > 90 minutes

Longer DIDO time assoc with increased

Mortality!

Reperfusion Therapy for Patients with STEMI