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ExTRACT-TIMI 25 E nox aparin and T hrombolysis R eperfusion for AC ute Myocardial Infarction T reatment–T hrombolysis I n M yocardial I nfarction Study 25

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ExTRACT-TIMI 25. E no x aparin and T hrombolysis R eperfusion for AC ute Myocardial Infarction T reatment – T hrombolysis I n M yocardial I nfarction Study 25. ExTRACT-TIMI 25: Background. - PowerPoint PPT Presentation

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Page 1: ExTRACT-TIMI 25

ExTRACT-TIMI 25

Enoxaparin and Thrombolysis Reperfusion for ACute Myocardial Infarction Treatment–Thrombolysis In Myocardial Infarction Study 25

Page 2: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Background

• In STEMI patients, prolonged infusion of UFH has not been shown to prevent reocclusion following angiographically successful fibrinolytic therapy– Therefore, current recommendations limit duration of infusion to 48 hours

• LMWH vs UFH provides a reliable level of anticoagulation without the need for therapeutic monitoring and with relatively greater proximal inhibition of the coagulation cascade

• ExTRACT-TIMI 25 compared LMWH (enoxaparin) and UFH as adjunctive therapy for fibrinolysis in STEMI– Enoxaparin was administered for duration of hospitalization and dosed according

to age and renal function

Antman EM et al. N Engl J Med. 2006;354:1477-88.LMWH = low-molecular-weight heparinUFH = unfractionated heparin

Page 3: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Study design

*Aged ≥75 yr: no IV bolus, 0.75 mg/kg sc q12h; CrCl <30 mL/min: ± IV bolus, 1.0 mg/kg sc q24h

Antman EM et al. Am Heart J. 2005;149:217-26.Antman EM et al. N Engl J Med. 2006;354:1477-88.

N = 20,506 fibrinolytic eligible, STEMI <6 hours

Primary end points:Efficacy: Death, MI in 30 days

Safety: TIMI major bleeding

Net clinical benefit:Death, MI, disabling stroke, nonfatal major bleed, ICH

Randomized, double-blind, double-dummy

ASA 150–325 mg, fibrinolytic (TNK, tPA, rPA, SK)

Enoxaparin 30 mg IV bolus, 1.0 mg/kg sc q12h*

median 7 days

UFH 60 U/kg IV bolus, 12 U/kg/h

median 2 days

Page 4: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Medical history and prior treatments

%

Enoxaparin(n = 10,256)

UFH(n = 10,223)

Hypertension 44.5 43.6

Hyperlipidemia 18.3 18.2

Smoking 47.3 47.4

Diabetes 15.2 15.0

Prior MI 13.2 12.9

Prior angina 28.1 28.0

Prior PCI 3.3 3.1

Long-term ASA 13.6 13.3

UFH <3 h prior to randomization 15.9 15.7

LMWH <7 d prior to randomization 0.4 0.5

Antman EM et al. N Engl J Med. 2006;354:1477-88.

Page 5: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Baseline characteristics

Enoxaparin(n = 10,256)

UFH(n = 10,223)

Age (years) 59.0 60.0

Age ≥75 years (%) 12.1 12.6

Male (%) 76.5 76.8

White race (%) 87.1 87.3

Weight (lb) 167.0 167.0

CrCl (mL/min) 82.3 82.0

Anterior MI (%) 43.6 44.2

Killip class I/II (%) 99.0 98.9

TIMI risk score ≤3 (%) 64.4 64.3

TIMI risk score >3 (%) 35.6 35.7

Antman EM et al. N Engl J Med. 2006;354:1477-88.

Page 6: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Baseline treatmentEnoxaparin(n = 10,256)

UFH(n = 10,223)

Time from symptom onset to startof fibrinolytic therapy (hr) 3.1 3.2

Fibrinolytic therapy (%)

Tenecteplase 19.3 19.7

Alteplase 54.7 54.5

Reteplase 5.5 5.5

Streptokinase 20.3 20.1

None 0.3 0.3

Time from fibrinolytic therapy to study drug (%)

≤30 min 97.0 97.1

>30 min 3.1 2.8Antman EM et al. N Engl J Med. 2006;354:1477-88.

Page 7: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Cardiac medications during hospitalization

%

Enoxaparin(n = 10,256)

UFH(n = 10,223)

Aspirin 94.8 95.4

Clopidogrel 27.2 28.7

β-Blocker 85.9 85.5

ACEI or ARB 80.0 79.3

Statin 69.5 69.5

Antman EM et al. N Engl J Med. 2006;354:1477-88.

Page 8: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Significant reduction in primary end point

Death, MI at 30 days

Antman EM et al. N Engl J Med. 2006;354:1477-88.

15

12

9

6

3

0

255 10 15 200 30

End point(%)

Days after randomization

Enoxaparin

UFH

RR 0.83(0.77–0.90)P < 0.001

Page 9: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Significant reduction in major secondary end point

Death, MI, urgent revascularization at 30 days

Antman EM et al. N Engl J Med. 2006;354:1477-88.

15

12

9

6

3

0

255 10 15 200 30

Enoxaparin

RR 0.81(0.75–0.87)P < 0.001

RR (48 hr) 0.88(0.79–0.98)

P = 0.02

End point(%)

UFH

2

Days after randomization

Page 10: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Safety outcomes at 30 days

Enoxaparin(n = 10,176)

UFH(n = 10,151)

Major bleeding* 2.1 1.4

Intracranial hemorrhage (ICH)

0.8 0.7

Minor bleeding 2.6 1.8

Major or minor bleeding

4.6 3.1

%

Antman EM et al. N Engl J Med. 2006;354:1477-88.*Primary safety outcome (includes ICH)

P

<0.001

0.14

<0.001

<0.001

0 1 2Relative risk (95% CI)

Favorsenoxaparin

FavorsUFH

Page 11: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Net clinical benefit at 30 days

Enoxaparin(n = 10,256)

UFH(n = 10,223)

Death, MI, disabling stroke

10.1 12.3

Death, MI, major bleeding

11.0 12.8

Death, MI, ICH 10.1 12.2

%

Antman EM et al. N Engl J Med. 2006;354:1477-88.

P

<0.001

<0.001

<0.001

0.75 1 1.25

Relative risk (95% CI)

Favorsenoxaparin

FavorsUFH

Page 12: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Overall results

• Primary efficacy end pointRate of death or MI was significantly lower with enoxaparin vs UFH (P < 0.001)

• Major secondary end pointRate of death, MI or urgent revascularization was significantly lower with enoxaparin vs UFH (P < 0.001)

• Safety outcomeRate of major bleeding* in both groups: 2.1% enoxaparin vs 1.4% UFH (P < 0.001)

Antman EM et al. N Engl J Med. 2006;354:1477-88.*TIMI criteria

Page 13: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Summary

• In STEMI patients, treatment with enoxaparin throughout the index of hospitalization vs UFH for48 hours demonstrated:– Superior reduction in ischemic events– Increase in episodes of major bleeding

• ExTRACT-TIMI 25 results show that treatment strategy with enoxaparin is preferable to the current standard of UFH to support fibrinolysis

Antman EM et al. N Engl J Med. 2006;354:1477-88.

Page 14: ExTRACT-TIMI 25

ExTRACT-TIMI 25: Clinical implications

-15

-7-6

+4

-20

-15

-10

-5

0

5

Events per1000 patients

Antman EM et al. N Engl J Med. 2006;354:1477-88.

Nonfatal MI

Urgentrevascularization Death

Nonfatal major

bleeding