The ASSENT 3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin,...

$: The ASSENT 3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT 3 randomised.$
The ASSENT 3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT 3 randomised The ASSENT 3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT 3 randomised trial. Lancet 2001;358:605-13. trial. Lancet 2001;358:605-13.

ASSENT 3ASSENT 3ASSENT 3ASSENT 3

Efficacy and Safety of Tenecteplase in Efficacy and Safety of Tenecteplase in Combination with Enoxaparin, Abciximab or Combination with Enoxaparin, Abciximab or

Unfractionated Heparin: the ASSENT-3 Unfractionated Heparin: the ASSENT-3 Randomised Trial in Acute Myocardial Randomised Trial in Acute Myocardial

InfarctionInfarction

The Assessment of the Safety and Efficacy of a New The Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 InvestigatorsThrombolytic Regimen (ASSENT)-3 Investigators


ASSENT 3: Inclusion CriteriaASSENT 3: Inclusion CriteriaASSENT 3: Inclusion CriteriaASSENT 3: Inclusion Criteria

• Inclusion criteria were identical to those of the Inclusion criteria were identical to those of the Assessment of the Safety and Efficacy of a New Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-2 trial:Thrombolytic Regimen (ASSENT)-2 trial:

Age 18 years or olderAge 18 years or older

Onset of symptoms within 6 hours before randomizationOnset of symptoms within 6 hours before randomization

ST-segment elevation of 1 mm or more in two or more limb ST-segment elevation of 1 mm or more in two or more limb leads, or 2 mm or more in two or more contiguous leads, or 2 mm or more in two or more contiguous precordial leads or left bundle-branch block.precordial leads or left bundle-branch block.


ASSENT 3: Exclusion CriteriaASSENT 3: Exclusion CriteriaASSENT 3: Exclusion CriteriaASSENT 3: Exclusion Criteria

Exclusion criteria on admission were: Exclusion criteria on admission were:

• Systolic blood pressure of more than 180 mm HgSystolic blood pressure of more than 180 mm Hg

• Diastolic blood pressure of more than 110 mm Hg, or both on Diastolic blood pressure of more than 110 mm Hg, or both on repeated measurementsrepeated measurements

• Use of abciximab or other glycoprotein IIb/IIIa inhibitors within the Use of abciximab or other glycoprotein IIb/IIIa inhibitors within the preceding seven dayspreceding seven days

• Major surgery, biopsy of a parenchymal organ or substantial Major surgery, biopsy of a parenchymal organ or substantial trauma within two monthstrauma within two months

• Any head or other trauma occurring after onset of current Any head or other trauma occurring after onset of current myocardial infarction; any known history of stroke, transient myocardial infarction; any known history of stroke, transient ischemic attack or dementia; any known structural damage to the ischemic attack or dementia; any known structural damage to the central nervous systemcentral nervous system

• Current therapy with oral anticoagulants; treatment with Current therapy with oral anticoagulants; treatment with unfractionated heparin unfractionated heparin 5,000 U or a therapeutic subcutaneous 5,000 U or a therapeutic subcutaneous dose of low-molecular-weight heparin within 6 hoursdose of low-molecular-weight heparin within 6 hours


ASSENT 3: Exclusion Criteria (continued)ASSENT 3: Exclusion Criteria (continued)ASSENT 3: Exclusion Criteria (continued)ASSENT 3: Exclusion Criteria (continued)

Exclusion criteria on admission were (continued): Exclusion criteria on admission were (continued):

• Known thrombocytopenia (Known thrombocytopenia (100,000 cells/100,000 cells/l)l)

• Known renal insufficiency (serum creatinine Known renal insufficiency (serum creatinine 2.5 mg% for men 2.5 mg% for men and and 2.0 mg% for women)2.0 mg% for women)

• Sustained cardiopulmonary resuscitation (more than 10 min) in Sustained cardiopulmonary resuscitation (more than 10 min) in previous two weeksprevious two weeks

• Pregnancy, lactation, or parturition in the previous 30 daysPregnancy, lactation, or parturition in the previous 30 days

• Active participation in another investigative drug or device study Active participation in another investigative drug or device study in the previous 30 days; previous enrolment in this studyin the previous 30 days; previous enrolment in this study

• Inability to follow the protocol and to comply with the follow-up Inability to follow the protocol and to comply with the follow-up requirementsrequirements


UFH IV bolusUFH IV bolusUFH IV bolusUFH IV bolusenoxaparin IV bolusenoxaparin IV bolusenoxaparin IV bolusenoxaparin IV bolus UFH IV bolusUFH IV bolusUFH IV bolusUFH IV bolus

Wt adj TNK-tPA Wt adj TNK-tPA full-dose IV bolusfull-dose IV bolusWt adj TNK-tPA Wt adj TNK-tPA

full-dose IV bolusfull-dose IV bolusWt adj TNK-tPA Wt adj TNK-tPA

full-dose IV bolusfull-dose IV bolusWt adj TNK-tPA Wt adj TNK-tPA

full-dose IV bolusfull-dose IV bolusabciximab IV bolusabciximab IV bolusabciximab IV bolusabciximab IV bolus

UFH IV infusion for UFH IV infusion for up to 48 hoursup to 48 hours

UFH IV infusion for UFH IV infusion for up to 48 hoursup to 48 hours

enoxaparin SC injections enoxaparin SC injections every 12 hours up to every 12 hours up to

discharge or discharge or revascularization revascularization

(max of 7 days)(max of 7 days)

enoxaparin SC injections enoxaparin SC injections every 12 hours up to every 12 hours up to

discharge or discharge or revascularization revascularization

(max of 7 days)(max of 7 days)

Wt adj TNK-tPA Wt adj TNK-tPA half-dose IV bolushalf-dose IV bolusWt adj TNK-tPA Wt adj TNK-tPA

half-dose IV bolushalf-dose IV bolus

abciximab IV infusion abciximab IV infusion for 12 hoursfor 12 hours

abciximab IV infusion abciximab IV infusion for 12 hoursfor 12 hours

UFH IV infusion UFH IV infusion for up to 48 hoursfor up to 48 hoursUFH IV infusion UFH IV infusion

for up to 48 hoursfor up to 48 hours

randomization 1:1:1randomization 1:1:1randomization 1:1:1randomization 1:1:1

ASSENT 3: Trial DesignASSENT 3: Trial DesignASSENT 3: Trial DesignASSENT 3: Trial Design

An international, multicenter, randomized (1:1:1), open-label, controlled, parallel-An international, multicenter, randomized (1:1:1), open-label, controlled, parallel-group study in patients with ST-elevation AMI presenting within 6 hours of symptom group study in patients with ST-elevation AMI presenting within 6 hours of symptom

onset, treated with 1 of 3 different reperfusion regimensonset, treated with 1 of 3 different reperfusion regimens


ASSENT 3: Primary EndpointsASSENT 3: Primary EndpointsASSENT 3: Primary EndpointsASSENT 3: Primary Endpoints

Primary Efficacy Endpoint:Primary Efficacy Endpoint: Composite of 30-day Composite of 30-day mortality or in-hospital reinfarction or in-hospital mortality or in-hospital reinfarction or in-hospital refractory ischemia. refractory ischemia.

Primary Efficacy Plus Safety Endpoint:Primary Efficacy Plus Safety Endpoint: Composite of Composite of 30-day mortality or in-hospital reinfarction or in-30-day mortality or in-hospital reinfarction or in-hospital refractory ischemia plus in-hospital hospital refractory ischemia plus in-hospital intracranial haemorrhage or in-hospital major bleeding intracranial haemorrhage or in-hospital major bleeding other than intracranial. other than intracranial.


Patients Randomized (ITT)Patients Randomized (ITT)

Female, (%)Female, (%)

Age (median years)Age (median years)

Previous MI (%)Previous MI (%)

Anterior MI (%)Anterior MI (%)

Diabetes (%)Diabetes (%)

ASSENT II97-98

ASSENT II97-98

1694916949

2323

6161

1616

4040

1616

2.82.8

GUSTO V99-01

GUSTO V99-01

1658816588

2525

6161

1515

3737

1616

2.72.7

GUSTO III95-97

GUSTO III95-97

1505915059

2727

6363

1818

4848

1616

2.72.7

InTIME II97-99

InTIME II97-99

1506015060

2525

6262

1616

4242

1414

2.92.9Median Time (hrs) Between Symptom and First Study RxMedian Time (hrs) Between Symptom and First Study Rx

GUSTO I90-93

GUSTO I90-93

3064730647

2525

6262

1717

3939

1515

2.82.8

ASSENT 300-01

ASSENT 300-01

20402040

2323

6161

1414

3939

1919

2.72.7

ASSENT 300-01

ASSENT 300-01

20172017

2424

6161

1313

3939

1818

2.72.7

ASSENT 300-01

ASSENT 300-01

20382038

2323

6161

1414

3838

1818

2.82.8

Baseline Demographics of Large Scale Baseline Demographics of Large Scale Thrombolytic TrialsThrombolytic Trials

Baseline Demographics of Large Scale Baseline Demographics of Large Scale Thrombolytic TrialsThrombolytic Trials


ASSENT 3: Primary Composite Endpoints ASSENT 3: Primary Composite Endpoints at at

Hospital Discharge and at 30 DaysHospital Discharge and at 30 Days

ASSENT 3: Primary Composite Endpoints ASSENT 3: Primary Composite Endpoints at at


Unfractionated Unfractionated 3 way3 wayEnoxaparinEnoxaparin AbciximabAbciximab HeparinHeparin PP Value Value(n=2040)(n=2040) (n=2017)(n=2017) (n=2038)(n=2038)

30-day mortality or30-day mortality or 11.411.4 11.111.1 15.415.4 <0.0001<0.0001in-hospital reinfarctionin-hospital reinfarction or in-hospital refractoryor in-hospital refractoryischemiaischemia

30-day mortality or30-day mortality or 13.813.8 14.214.2 17.017.0 0.00810.0081in-hospital reinfarctionin-hospital reinfarctionor in-hospital refractory or in-hospital refractory ischemia or in-hospital ICH ischemia or in-hospital ICH or in-hospital major bleedsor in-hospital major bleeds(other than ICH)(other than ICH)

Data are percentages and 95% confidence intervals. ICH, intracranial hemorrhage.Data are percentages and 95% confidence intervals. ICH, intracranial hemorrhage.


ASSENT 3: Days to Death or Reinfarction ASSENT 3: Days to Death or Reinfarction or Refractory Ischemiaor Refractory Ischemia

ASSENT 3: Days to Death or Reinfarction ASSENT 3: Days to Death or Reinfarction or Refractory Ischemiaor Refractory Ischemia

Days to Death or Reinfarction or Refractory IschemiaDays to Death or Reinfarction or Refractory IschemiaDays to Death or Reinfarction or Refractory IschemiaDays to Death or Reinfarction or Refractory Ischemia

Pro

babili

ty (

%)

Pro

babili

ty (

%)

Pro

babili

ty (

%)

Pro

babili

ty (

%)

0000

2222

4444

6666

8888

10101010

14141414

12121212

16161616

18181818

20202020

5555 10101010 15151515 20202020 25252525 30303030

UnfractionatedUnfractionatedHeparinHeparinUnfractionatedUnfractionatedHeparinHeparin

EnoxaparinEnoxaparinEnoxaparinEnoxaparin

AbciximabAbciximabAbciximabAbciximab

Log-rank test: Log-rank test: PP=0.0001=0.0001Log-rank test: Log-rank test: PP=0.0001=0.0001

0000

15.4%

11.4%11.1%


ASSENT 3: Days to Death or Reinfarction ASSENT 3: Days to Death or Reinfarction or Refractory Ischemia or ICH or Major or Refractory Ischemia or ICH or Major

BleedingBleeding

ASSENT 3: Days to Death or Reinfarction ASSENT 3: Days to Death or Reinfarction or Refractory Ischemia or ICH or Major or Refractory Ischemia or ICH or Major

BleedingBleeding

Days to Death or Reinfarction or Refractory Ischemia or ICH or Major BleedingDays to Death or Reinfarction or Refractory Ischemia or ICH or Major BleedingDays to Death or Reinfarction or Refractory Ischemia or ICH or Major BleedingDays to Death or Reinfarction or Refractory Ischemia or ICH or Major Bleeding

Pro

babili

ty (

%)

Pro

babili

ty (

%)

Pro

babili

ty (

%)

Pro

babili

ty (

%)

0000

2222

4444

6666

8888

10101010

14141414

12121212

16161616

18181818

20202020

5555 10101010 15151515 20202020 25252525 30303030

UnfractionatedUnfractionatedHeparinHeparinUnfractionatedUnfractionatedHeparinHeparin

AbciximabAbciximabAbciximabAbciximab

EnoxaparinEnoxaparinEnoxaparinEnoxaparin

Log-rank test: Log-rank test: PP=0.0062=0.0062Log-rank test: Log-rank test: PP=0.0062=0.0062

0000

13.8%14.2%

17.0%


ASSENT 3: 30 Day Mortality, Recurrent ASSENT 3: 30 Day Mortality, Recurrent MI, Refractory IschemiaMI, Refractory Ischemia


11.4% 11.1%

15.4%

0.0%

5.0%

10.0%

15.0%

20.0%

TNK + TNK + TNK

11.4% 11.1%

15.4%

0.0%

5.0%

10.0%

15.0%

20.0%

TNK + TNK + TNKEnoxaparinEnoxaparin AbciximabAbciximab

% R

isk

of

30 D

ay D

/ M

I /

Ref

Isc

h%

Ris

k o

f 30

Day

D /

MI

/ R

ef I

sch

3 way P=0.00013 way P=0.00013 way P=0.00013 way P=0.0001

p=0.0002*p=0.0002*p=0.0009*p=0.0009*

*P values are the Bonferroni p-values after correcting for multiple comparisons. The uncorrected p-values were p=0.0002 for the enox vs UFH comparison, and <0.0001 for the abcix vs UFH comparison.*P values are the Bonferroni p-values after correcting for multiple comparisons. The uncorrected p-values were p=0.0002 for the enox vs UFH comparison, and <0.0001 for the abcix vs UFH comparison.




13.8% 14.2%

17.0%

0.0%

5.0%

10.0%

15.0%

20.0%

TNK + TNK + TNK

13.8% 14.2%

17.0%

0.0%

5.0%

10.0%

15.0%

20.0%


3 way p=0.00623 way p=0.00623 way p=0.00623 way p=0.0062

ASSENT 3: 30 Day Mortality, Recurrent ASSENT 3: 30 Day Mortality, Recurrent MI, Refractory Ischemia, Major MI, Refractory Ischemia, Major

Bleeding, ICHBleeding, ICH

ASSENT 3: 30 Day Mortality, Recurrent ASSENT 3: 30 Day Mortality, Recurrent MI, Refractory Ischemia, Major MI, Refractory Ischemia, Major

Bleeding, ICHBleeding, ICH%

Ris

k o

f 30

Day

D /

MI

/ R

ef I

sch

/ M

aj

Ble

ed

/ I

CH

% R

isk

of

30 D

ay D

/ M

I /

Ref

Isc

h /

Ma

j B

lee

d /

IC

H

p=0.057*p=0.057*p=0.0146*p=0.0146*

*P values are the Bonferroni p-values after correcting for multiple comparisons. The uncorrected p-values were p=0.0037 for the enox vs UFH comparison, and 0.0142 for the abcix vs UFH comparison.*P values are the Bonferroni p-values after correcting for multiple comparisons. The uncorrected p-values were p=0.0037 for the enox vs UFH comparison, and 0.0142 for the abcix vs UFH comparison.


Death at 30 Days orDeath at 30 Days or ENOX orENOX orIn-Hospital Reinfarction orIn-Hospital Reinfarction or ENOX orENOX or Relative RiskRelative Risk ABCIXABCIX UFHUFHRefractory Ischemia (%)Refractory Ischemia (%) UFHUFH ABCIXABCIX (95% CI)(95% CI) BetterBetter BetterBetter

ASSENT 3: Odds Ratios for Death at 30 ASSENT 3: Odds Ratios for Death at 30 Days or In-Hospital Reinfarction or Days or In-Hospital Reinfarction or

Refractory IschemiaRefractory Ischemia

ASSENT 3: Odds Ratios for Death at 30 ASSENT 3: Odds Ratios for Death at 30 Days or In-Hospital Reinfarction or Days or In-Hospital Reinfarction or

Refractory IschemiaRefractory Ischemia

0.50.5 11 22

ENOX vs UFHENOX vs UFH

ABCIX vs UFHABCIX vs UFH

UFH, unfractionated heparin; ENOX, enoxaparin; ABCIX, abciximab.UFH, unfractionated heparin; ENOX, enoxaparin; ABCIX, abciximab.

Overall event rateOverall event rate 15.415.4 11.411.4 0.74 (0.63, 0.87)0.74 (0.63, 0.87)11.111.1 0.72 (0.61, 0.84)0.72 (0.61, 0.84)

GenderGenderMaleMale 14.814.8 10.410.4 0.70 (0.58, 0.84)0.70 (0.58, 0.84)

9.89.8 0.66 (0.55, 0.80)0.66 (0.55, 0.80)FemaleFemale 17.417.4 15.115.1 0.87 (0.65, 1.17)0.87 (0.65, 1.17)

14.814.8 0.85 (0.64, 1.14)0.85 (0.64, 1.14)

Infarct locationInfarct locationAnteriorAnterior 19.419.4 14.614.6 0.75 (0.60, 0.94)0.75 (0.60, 0.94)

13.613.6 0.70 (0.56, 0.88)0.70 (0.56, 0.88)OtherOther 13.013.0 9.59.5 0.72 (0.58, 0.91)0.72 (0.58, 0.91)

9.59.5 0.73 (0.58, 0.91)0.73 (0.58, 0.91)

Time to TNK-tPA (h)Time to TNK-tPA (h)0-20-2 16.816.8 13.013.0 0.77 (0.59, 1.01)0.77 (0.59, 1.01)

8.98.9 0.53 (0.38, 0.74)0.53 (0.38, 0.74)>2-4>2-4 14.214.2 9.89.8 0.69 (0.53, 0.84)0.69 (0.53, 0.84)

10.910.9 0.76 (0.60, 0.96)0.76 (0.60, 0.96)>4>4 16.316.3 12.612.6 0.77 (0.56, 1.06)0.77 (0.56, 1.06)

13.313.3 0.82 (0.60, 1.10)0.82 (0.60, 1.10)


ASSENT 3: Odds Ratio for Death at 30 ASSENT 3: Odds Ratio for Death at 30 Days or In-Hospital Reinfarction or Days or In-Hospital Reinfarction or

Refractory Ischemia (Cont.)Refractory Ischemia (Cont.)

ASSENT 3: Odds Ratio for Death at 30 ASSENT 3: Odds Ratio for Death at 30 Days or In-Hospital Reinfarction or Days or In-Hospital Reinfarction or

Refractory Ischemia (Cont.)Refractory Ischemia (Cont.)




Death at 30 Days orDeath at 30 Days or ENOX orENOX orIn-Hospital Reinfarction orIn-Hospital Reinfarction or ENOX orENOX or Relative RiskRelative Risk ABCIXABCIX UFHUFHRefractory Ischemia (%)Refractory Ischemia (%) UFHUFH ABCIXABCIX (95% CI)(95% CI) BetterBetter BetterBetter

Age (years)Age (years)≤≤7575 13.813.8 10.010.0 0.73 (0.61, 0.87)0.73 (0.61, 0.87)

9.09.0 0.65 (0.54, 0.78)0.65 (0.54, 0.78)>75>75 26.226.2 20.920.9 0.80 (0.59, 1.09)0.80 (0.59, 1.09)

26.626.6 1.02 (0.76, 1.36)1.02 (0.76, 1.36)

DiabetesDiabetesYesYes 13.813.8 12.412.4 0.90 (0.62, 1.30)0.90 (0.62, 1.30)

18.018.0 1.31 (0.93, 1.84)1.31 (0.93, 1.84)NoNo 15.815.8 11.211.2 0.71 (0.60, 0.85)0.71 (0.60, 0.85)

9.59.5 0.60 (0.50, 0.72)0.60 (0.50, 0.72)

0.50.5 11 22

* There was a statistically significant interaction between treatment with abciximab and diabetes, such that diabetics had poorer outcomes with abciximab therapy (p=0.0004).* There was a statistically significant interaction between treatment with abciximab and diabetes, such that diabetics had poorer outcomes with abciximab therapy (p=0.0004).

*


Death at 30 Days or In-HospitalDeath at 30 Days or In-Hospital ENOX orENOX orReinfarction or Refractory IschemiaReinfarction or Refractory Ischemia ENOX orENOX or Relative RiskRelative Risk ABCIXABCIX UFHUFHor ICH or Major Bleeding (%)or ICH or Major Bleeding (%) UFHUFH ABCIXABCIX (95% CI)(95% CI) BetterBetter BetterBetter

Overall event rateOverall event rate 17.017.0 13.713.7 0.81 (0.70, 0.93)0.81 (0.70, 0.93)14.214.2 0.84 (0.73, 0.97)0.84 (0.73, 0.97)

GenderGenderMaleMale 16.216.2 11.911.9 0.73 (0.61, 0.88)0.73 (0.61, 0.88)

12.5512.55 0.77 (0.65, 0.92)0.77 (0.65, 0.92)FemaleFemale 19.919.9 20.120.1 1.01 (0.78, 1.31)1.01 (0.78, 1.31)

20.020.0 1.01 (0.78, 1.30)1.01 (0.78, 1.30)

Infarct locationInfarct locationAnteriorAnterior 20.520.5 16.016.0 0.78 (0.63, 0.96)0.78 (0.63, 0.96)

16.616.6 0.83 (0.67, 1.02)0.83 (0.67, 1.02)OtherOther 15.015.0 12.312.3 0.82 (0.67, 1.00)0.82 (0.67, 1.00)

12.812.8 0.85 (0.70, 1.03)0.85 (0.70, 1.03)

Time to TNK-tPA (h)Time to TNK-tPA (h)0-20-2 18.318.3 16.216.2 0.88 (0.69, 1.14)0.88 (0.69, 1.14)

13.013.0 0.71 (0.53, 0.95)0.71 (0.53, 0.95)>2-4>2-4 15.815.8 11.911.9 0.75 (0.60, 0.94)0.75 (0.60, 0.94)

13.513.5 0.87 (0.70, 1.07)0.87 (0.70, 1.07)>4>4 18.018.0 13.913.9 0.77 (0.57, 1.05)0.77 (0.57, 1.05)

16.916.9 0.94 (0.71, 1.23)0.94 (0.71, 1.23)

ASSENT 3: Odds Ratios for Days to Death or ASSENT 3: Odds Ratios for Days to Death or Reinfarction or Refractory Ischemia or ICH Reinfarction or Refractory Ischemia or ICH

or Major Bleedingor Major Bleeding

ASSENT 3: Odds Ratios for Days to Death or ASSENT 3: Odds Ratios for Days to Death or Reinfarction or Refractory Ischemia or ICH Reinfarction or Refractory Ischemia or ICH

or Major Bleedingor Major Bleeding

0.50.5 11 22





ASSENT 3: Odds Ratio for Death, ASSENT 3: Odds Ratio for Death, Reinfarction or Reinfarction or

Refractory Ischemia, ICH or Major Bleeding Refractory Ischemia, ICH or Major Bleeding (Cont.)(Cont.)

ASSENT 3: Odds Ratio for Death, ASSENT 3: Odds Ratio for Death, Reinfarction or Reinfarction or

Refractory Ischemia, ICH or Major Bleeding Refractory Ischemia, ICH or Major Bleeding (Cont.)(Cont.)

Death at 30 Days or In-HospitalDeath at 30 Days or In-Hospital ENOX orENOX orReinfarction or Refractory IschemiaReinfarction or Refractory Ischemia ENOX orENOX or Relative RiskRelative Risk ABCIXABCIX UFHUFHor ICH or Major Bleeding (%)or ICH or Major Bleeding (%) UFHUFH ABCIXABCIX (95% CI)(95% CI) BetterBetter BetterBetter

Age (years)Age (years)≤≤7575 15.415.4 12.012.0 0.78 (0.66, 0.92)0.78 (0.66, 0.92)

11.211.2 0.74 (0.63, 0.88)0.74 (0.63, 0.88)>75>75 28.028.0 25.525.5 0.91 (0.69, 1.20)0.91 (0.69, 1.20)

36.936.9 1.30 (1.01, 1.68)1.30 (1.01, 1.68)

DiabetesDiabetesYesYes 16.516.5 13.913.9 0.84 (0.60, 1.19)0.84 (0.60, 1.19)

22.322.3 1.35 (1.00, 1.82)1.35 (1.00, 1.82)NoNo 17.217.2 13.713.7 0.80 (0.68, 0.94)0.80 (0.68, 0.94)

12.512.5 0.74 (0.62, 0.87)0.74 (0.62, 0.87)

0.50.5 11 22ENOX vs UFHENOX vs UFH



*There was a statistically significant interaction between treatment with abciximab and diabetes, such that diabetics had poorer outcomes with abciximab therapy (p=0.0007), and likewise, patients over the age of 75 had poorer outcomes with abciximab (p=0.0010).

*There was a statistically significant interaction between treatment with abciximab and diabetes, such that diabetics had poorer outcomes with abciximab therapy (p=0.0007), and likewise, patients over the age of 75 had poorer outcomes with abciximab (p=0.0010).


25.5%

36.9%

28.0%

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

35.0%

40.0%

TNK + TNK + TNK

25.5%

36.9%

28.0%

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

35.0%

40.0%


ASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: 30 Day Mortality%

Ris

k o

f 30

Day

Eff

icac

y &

Saf

ety

En

dp

oin

t%

Ris

k o

f 30

Day

Eff

icac

y &

Saf

ety

En

dp

oin

t

ASSENT 3: Primary Efficacy and Safety Endpoint of ASSENT 3: Primary Efficacy and Safety Endpoint of Death, Reinfarction or Refractory Ischemia, ICH or Death, Reinfarction or Refractory Ischemia, ICH or

Major Bleeding in Patients > 75 Years of AgeMajor Bleeding in Patients > 75 Years of Age

ASSENT 3: Primary Efficacy and Safety Endpoint of ASSENT 3: Primary Efficacy and Safety Endpoint of Death, Reinfarction or Refractory Ischemia, ICH or Death, Reinfarction or Refractory Ischemia, ICH or

Major Bleeding in Patients > 75 Years of AgeMajor Bleeding in Patients > 75 Years of Age

*There was a statistically significant interaction between treatment with abciximab and age such that patients over the age of 75 had poorer outcomes with abciximab (p=0.0010).*There was a statistically significant interaction between treatment with abciximab and age such that patients over the age of 75 had poorer outcomes with abciximab (p=0.0010).

*p=0.001


13.9%

22.3%

16.5%

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

TNK + TNK + TNK

13.9%

22.3%

16.5%

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%


ASSENT 3: Primary Efficacy and Safety Endpoint of ASSENT 3: Primary Efficacy and Safety Endpoint of Death, Reinfarction or Refractory Ischemia, ICH or Major Death, Reinfarction or Refractory Ischemia, ICH or Major

Bleeding in Patients with DiabetesBleeding in Patients with Diabetes

ASSENT 3: Primary Efficacy and Safety Endpoint of ASSENT 3: Primary Efficacy and Safety Endpoint of Death, Reinfarction or Refractory Ischemia, ICH or Major Death, Reinfarction or Refractory Ischemia, ICH or Major

Bleeding in Patients with DiabetesBleeding in Patients with Diabetes%

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Day

Eff

icac

y &

Saf

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En

dp

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Day

Eff

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*There was a statistically significant interaction between treatment with abciximab and diabetes, such that diabetics had poorer outcomes with abciximab therapy (p=0.0007).*There was a statistically significant interaction between treatment with abciximab and diabetes, such that diabetics had poorer outcomes with abciximab therapy (p=0.0007).

*p=0.0007


ASSENT 3: Frequency of Individual ASSENT 3: Frequency of Individual Endpoints at Endpoints at


ASSENT 3: Frequency of Individual ASSENT 3: Frequency of Individual Endpoints at Endpoints at


Unfractionated Unfractionated 3 way3 wayEnoxaparinEnoxaparin AbciximabAbciximab HeparinHeparin PP Value Value(n=2040)(n=2040) (n=2017)(n=2017) (n=2038)(n=2038)

Death at 30 daysDeath at 30 days 5.45.4 6.66.6 6.06.0 0.250.25

In-hospital reinfarctionIn-hospital reinfarction 2.72.7 2.22.2 4.24.2 0.00090.0009

In-hospital refractoryIn-hospital refractory 4.64.6 3.23.2 6.56.5 <0.0001<0.0001ischemiaischemia

In-hospital ICHIn-hospital ICH 0.90.9 0.90.9 0.90.9 0.980.98

Major bleedingMajor bleeding 3.03.0 4.34.3 2.22.2 0.00050.0005(other than ICH)(other than ICH)

Data are percentages. ICH, intracranial hemorrhage.Data are percentages. ICH, intracranial hemorrhage.


3.0%

4.3%

2.2%

0.0%

5.0%

TNK + TNK + TNK

3.0%

4.3%

2.2%

0.0%

5.0%


ASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: Risk of Major BleedingASSENT 3: Risk of Major BleedingASSENT 3: Risk of Major BleedingASSENT 3: Risk of Major Bleeding%

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% R

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3 Way p = 0.0053 Way p = 0.005

p=0.0002p=NS


ASSENT 3: Incidence of In-Hospital ASSENT 3: Incidence of In-Hospital Thrombocytopenia and Noncerebral Thrombocytopenia and Noncerebral

Bleeding ComplicationsBleeding Complications

ASSENT 3: Incidence of In-Hospital ASSENT 3: Incidence of In-Hospital Thrombocytopenia and Noncerebral Thrombocytopenia and Noncerebral

Bleeding ComplicationsBleeding Complications

UnfractionatedUnfractionated EnoxaparinEnoxaparin AbciximabAbciximab HeparinHeparin PP Value Value

(n=2040)(n=2040) (n=2017)(n=2017) (n=2038)(n=2038) 3 way3 way

Any thrombocytopeniaAny thrombocytopenia 1.21.2 3.23.2 1.31.3 <0.0001<0.0001

ThrombocytopeniaThrombocytopenia <0.0001<0.0001<20,000 cells/µL<20,000 cells/µL 0.10.1 0.50.5 0.20.220,000 to 50,000 cells/µL20,000 to 50,000 cells/µL 0.20.2 0.60.6 0.20.250,000 to <100,000 cells/µL50,000 to <100,000 cells/µL 0.90.9 2.02.0 1.01.0

Bleeding episodesBleeding episodesTotalTotal 25.625.6 39.739.7 21.121.1 <0.0001<0.0001MajorMajor 3.03.0 4.34.3 2.22.2 0.00050.0005MinorMinor 22.622.6 35.435.4 18.818.8 <0.0001<0.0001

Blood transfusionBlood transfusion 3.43.4 4.24.2 2.32.3 0.00320.0032

****

* While 3 way p value is significant, Enoxaparin vs UFH comparison p=NS* While 3 way p value is significant, Enoxaparin vs UFH comparison p=NS


13.3%

4.1%

0.0%

5.0%

10.0%

15.0%

TNK + TNK

13.3%

4.1%

0.0%

5.0%

10.0%

15.0%

TNK + TNKAbciximabAbciximab

ASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: Risk of Major Bleeding ASSENT 3: Risk of Major Bleeding in Patients Over 75 Yearsin Patients Over 75 Years

ASSENT 3: Risk of Major Bleeding ASSENT 3: Risk of Major Bleeding in Patients Over 75 Yearsin Patients Over 75 Years%

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% R

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7.0%

2.2%

0.0%

5.0%

10.0%

TNK + TNK

7.0%

2.2%

0.0%

5.0%

10.0%

TNK + TNKAbciximabAbciximab

ASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: 30 Day MortalityASSENT 3: Risk of Major Bleeding ASSENT 3: Risk of Major Bleeding in Patients With Diabetesin Patients With Diabetes

ASSENT 3: Risk of Major Bleeding ASSENT 3: Risk of Major Bleeding in Patients With Diabetesin Patients With Diabetes%

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ASSENT 3: Study Group Conclusions ASSENT 3: Study Group Conclusions Regarding TNK + Abciximab TherapyRegarding TNK + Abciximab TherapyASSENT 3: Study Group Conclusions ASSENT 3: Study Group Conclusions Regarding TNK + Abciximab TherapyRegarding TNK + Abciximab Therapy

• ““The results obtained with half-dose tenecteplase plus The results obtained with half-dose tenecteplase plus abciximab are very similar to those with half-dose abciximab are very similar to those with half-dose reteplase and abciximab seen in GUSTO-V.”reteplase and abciximab seen in GUSTO-V.”

• ““In both trials, these benefits are obtained at the cost In both trials, these benefits are obtained at the cost of a higher rate of major bleeding complications and of a higher rate of major bleeding complications and blood transfusions”. blood transfusions”.

• ““No benefit and perhaps even harm was observed in No benefit and perhaps even harm was observed in patients above 75 years and in diabetics”. patients above 75 years and in diabetics”.

• ““Taken together they suggest that caution should be Taken together they suggest that caution should be exercised regarding the use of conjunctive therapy exercised regarding the use of conjunctive therapy with abciximab in elderly patients with an acute with abciximab in elderly patients with an acute myocardial infarction treated with a fibrinolytic agent.”myocardial infarction treated with a fibrinolytic agent.”


ASSENT 3: Conclusions Regarding ASSENT 3: Conclusions Regarding EnoxaparinEnoxaparin

ASSENT 3: Conclusions Regarding ASSENT 3: Conclusions Regarding EnoxaparinEnoxaparin

• ““In view of the present data and the ease of In view of the present data and the ease of administration, enoxaparin might be considered an administration, enoxaparin might be considered an attractive alternative anticoagulant treatment when attractive alternative anticoagulant treatment when given in combination with tenecteplase”. given in combination with tenecteplase”.


ASSENT 3: Unanswered QuestionsASSENT 3: Unanswered QuestionsASSENT 3: Unanswered QuestionsASSENT 3: Unanswered Questions

• ““Whether enoxaparin is a desirable anticoagulant in Whether enoxaparin is a desirable anticoagulant in conjunction with less fibrin-specific agents or whether conjunction with less fibrin-specific agents or whether enoxaparin can replace unfractionated heparin in enoxaparin can replace unfractionated heparin in combination with a platelet glycoprotein IIb/IIIa combination with a platelet glycoprotein IIb/IIIa inhibitor and what role various pharmacologic inhibitor and what role various pharmacologic combinations will ultimately have in conjunction with combinations will ultimately have in conjunction with early coronary intervention needs to be determined”.early coronary intervention needs to be determined”.

The ASSENT 3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin,...

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