The ASSENT 3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the 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. ASSENT 3 randomised trial. Lancet 2001;358:605-13. ASSENT 3 ASSENT 3 Efficacy and Safety of Tenecteplase in Efficacy and Safety of Tenecteplase in Combination with Enoxaparin, Abciximab Combination with Enoxaparin, Abciximab or Unfractionated Heparin: the ASSENT-3 or Unfractionated Heparin: the ASSENT-3 Randomised Trial in Acute Myocardial Randomised Trial in Acute Myocardial Infarction Infarction The Assessment of the Safety and Efficacy of a The Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 New Thrombolytic Regimen (ASSENT)-3 Investigators Investigators
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The ASSENT 3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT 3 randomised.
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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
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.
• 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.
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.
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
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.
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
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.
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
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
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.
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.
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.
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
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 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
Hospital Discharge and at 30 DaysHospital Discharge and at 30 Days
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.
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 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
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 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
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 3: 30 Day Mortality, Recurrent ASSENT 3: 30 Day Mortality, Recurrent MI, Refractory IschemiaMI, Refractory Ischemia
ASSENT 3: 30 Day Mortality, Recurrent ASSENT 3: 30 Day Mortality, Recurrent MI, Refractory IschemiaMI, Refractory Ischemia
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.
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 3: 30 Day Mortality, Recurrent ASSENT 3: 30 Day Mortality, Recurrent MI, Refractory IschemiaMI, Refractory Ischemia
ASSENT 3: 30 Day Mortality, Recurrent ASSENT 3: 30 Day Mortality, Recurrent MI, Refractory IschemiaMI, Refractory Ischemia
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.
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.
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
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 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
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)
* 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).
*
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.
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
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
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 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)
*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).
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 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
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 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%
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
*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
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 3: Frequency of Individual ASSENT 3: Frequency of Individual Endpoints at Endpoints at
Hospital Discharge and at 30 DaysHospital Discharge and at 30 Days
ASSENT 3: Frequency of Individual ASSENT 3: Frequency of Individual Endpoints at Endpoints at
Hospital Discharge and at 30 DaysHospital Discharge and at 30 Days
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.
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 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%
Ris
k o
f M
ajo
r H
emo
rrh
age
% R
isk
of
Maj
or
Hem
orr
hag
e
3 Way p = 0.0053 Way p = 0.005
p=0.0002p=NS
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 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
* 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
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.
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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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.
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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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 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.”
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.
• ““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”.
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.
• ““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”.