Coronary Artery Disease
Conditions
Brief summary
The purpose of this study is to provide information of the relative potency of prasugrel and clopidogrel on platelet function studies, inflammation, and myocyte necrosis in subjects undergoing elective percutaneous coronary intervention (PCI).
Interventions
DRUGPrasugrel
Administered orally
DRUGClopidogrel
Administered orally
DRUGPlacebo for Prasugrel
Administered orally
DRUGPlacebo for Clopidogrel
Administered orally
Sponsors
Daiichi Sankyo
The TIMI Study Group
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects greater than or equal to 18 years of age undergoing cardiac catheterization with planned percutaneous coronary intervention (if coronary anatomy is suitable) for an indication of chest pain +/or anginal equivalent felt by the treating physician to be related to coronary ischemia. * At least one of the following (a through c): 1. Functional study (exercise, or pharmacologic) within the past 8 weeks consistent with ischemia as manifested by at least one of the following: 1. A reversible defect on nuclear imaging. 2. A reversible wall-motion abnormality by echocardiography. 3. Horizontal or down-sloping ST-depressions greater than 1 mm on electrocardiogram (ECG) (if no imaging performed). 2. Prior coronary revascularization \[percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)\]. 3. A cardiac catheterization with at least one coronary artery lesion amenable to PCI (not yet performed) within 14 days prior to enrollment.
Exclusion criteria
* Known creatine kinase-myocardial bands (CK-MB)or cardiac troponin greater than the upper limit of normal at time of screening * Planned PCI for acute myocardial infarction (MI) or planned PCI within 48 hours of fibrinolytic therapy for ST segment elevation myocardial infarction (STEMI) * Have cardiogenic shock at the time of screening (systolic blood pressure 90 mm Hg associated with clinical evidence of end-organ hypoperfusion, or subjects requiring vasopressors to maintain systolic blood pressure over 90 mm Hg and associated with clinical evidence of end-organ hypoperfusion). * Refractory ventricular arrhythmias * Have New York Heart Association Class IV congestive heart failure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) at 6 Hours After the Loading Dose | 6 hours after loading dose | IPA was defined as (1 - \[maximal platelet aggregation(MPA) at 6 hours after study drug treatment\]/\[MPA before drug treatment\]) x 100. |
| Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate After 14 Days of Maintenance Dose Treatment | after 14 days of maintenance dosing | Measures IPA during maintenance dosing before and after cross-over for each therapy. IPA was defined as (1 - \[maximal platelet aggregation(MPA) at 14 days after study drug treatment\]/\[MPA before drug treatment\]) x 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the Crossover Maintenance Dose Phase | 14 days after cross-over | Non-CABG-related TIMI major bleeding was any intracranial hemorrhage OR any clinically overt bleeding associated with a fall in hemoglobin \>=5 gm/dL. Non-CABG-related TIMI minor bleeding was any clinically overt bleeding associated with a fall in hemoglobin \>=3 gm/dL but \<5 gm/dL. |
| Number of Participants With Major Adverse Cardiac Events (MACE) During the First Maintenance Dose Phase | after 14 days of treatment (before cross-over) | Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization |
| Number of Participants With Major Adverse Cardiac Events During the Crossover Maintenance Dose Phase | 14 days after cross-over | Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization |
| Number of Hyporesponsive Participants at 6 Hours After the Loading Dose | 6 hours after loading dose | Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20% |
| Number of Hyporesponsive Participants at the End of the First Maintenance Dose Phase | From loading dose to day 15 | Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20% |
| Number of Hyporesponsive Participants at the End of the Crossover Maintenance Dose Phase | 14 days after cross-over | Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20% |
| Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 2 Hours After the Loading Dose | 2 hours after loading dose | VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect. |
| Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate at 2 Hours After the Loading Dose | 2 hours after loading dose | IPA was defined as (1 - \[maximal platelet aggregation (MPA) at 2 hours after study drug treatment\]/\[MPA before drug treatment\]) x 100. |
| Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) 18 to 24 Hours After the Loading Dose | 18 to 24 hours after loading dose | VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean flourescence index. A lower PRI indicates greater antiplatelet effect. |
| Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) After 14 Days of Maintenance Dose Treatment | after 14 days of maintenance dosing | VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect. |
| Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) at 6 Hours After the Loading Dose | 6 hours after loading dose | Mean CK-MB at 6 hours after loading dose. CK-MB is a biomarker for myonecrosis |
| Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) 18 to 24 Hours After the Loading Dose | 18 to 24 hours after loading dose | Mean CK-MB at 18-24 hours after loading dose. CK-MB is a biomarker for myonecrosis. |
| Myonecrosis Measure: Cardiac Troponin at 6 Hours After the Loading Dose | 6 hours after loading dose | Mean troponin level at 6 hours after the loading dose. Troponin is a biomarker for myonecrosis. |
| Myonecrosis Measure: Cardiac Troponin 18 to 24 Hours After the Loading Dose | 18 to 24 hours after loading dose | Mean troponin level at 18 to 24 hours after the loading dose. Troponin is a biomarker for myonecrosis. |
| Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 6 Hours After the Loading Dose | 6 hours after loading dose | VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect. |
| Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the First Maintenance Dose Phase | after 14 days of treatment (before cross-over) | Non-CABG-related TIMI major bleeding was any intracranial hemorrhage OR any clinically overt bleeding associated with a fall in hemoglobin \>=5 gm/dL. Non-CABG-related TIMI minor bleeding was any clinically overt bleeding associated with a fall in hemoglobin \>=3 gm/dL but \<5 gm/dL. |
Countries
France, Germany, Israel, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel to Clopidogrel One time oral loading dose (LD) of 60-mg prasugrel and placebo matched to clopidogrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by a once daily 10-mg prasugrel and placebo matched to clopidogrel (prasugrel maintenance dose) taken orally for 14 days. Patients cross-over to a once daily 150-mg clopidogrel and placebo matched to prasugrel (clopidogrel maintenance dose) taken orally for the next 14 days. | 102 |
| Clopidogrel to Prasugrel One time oral loading dose (LD) of 600-mg clopidogrel and placebo matched to prasugrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by a once daily 150-mg clopidogrel and placebo matched to prasugrel (clopidogrel maintenance dose) for 14 days. Patients cross-over to a once daily 10-mg prasugrel and placebo matched to clopidogrel (prasugrel maintenance dose) taken orally for the next 14 days. | 99 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Maintenance Dose Phase | Not a PCI patient | 47 | 42 |
| First Maintenance Dose Phase | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Prasugrel to Clopidogrel | Clopidogrel to Prasugrel | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 56 Participants | 52 Participants | 108 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 47 Participants | 93 Participants |
| Age Continuous | 64.0 years STANDARD_DEVIATION 10.73 | 63.8 years STANDARD_DEVIATION 9.38 | 63.9 years STANDARD_DEVIATION 10.06 |
| Race/Ethnicity, Customized African | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Caucasian | 97 participants | 94 participants | 191 participants |
| Race/Ethnicity, Customized Native American | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized West Asian | 0 participants | 1 participants | 1 participants |
| Region of Enrollment France | 3 participants | 3 participants | 6 participants |
| Region of Enrollment Germany | 55 participants | 53 participants | 108 participants |
| Region of Enrollment Israel | 15 participants | 13 participants | 28 participants |
| Region of Enrollment United States | 29 participants | 30 participants | 59 participants |
| Sex: Female, Male Female | 29 Participants | 22 Participants | 51 Participants |
| Sex: Female, Male Male | 73 Participants | 77 Participants | 150 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 40 / 102 | 40 / 99 | 16 / 55 | 12 / 53 |
| serious Total, serious adverse events | 8 / 102 | 7 / 99 | 1 / 55 | 3 / 53 |
Outcome results
Primary
Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) at 6 Hours After the Loading Dose
IPA was defined as (1 - \[maximal platelet aggregation(MPA) at 6 hours after study drug treatment\]/\[MPA before drug treatment\]) x 100.
Time frame: 6 hours after loading dose
Population: Consists of all patients who received a loading dose of the study drug, did not receive a glycoprotein (GP) IIb/IIIa antagonist, and had evaluable pre-treatment and 6 hour MPA measurements.~Patients had received a single loading dose of either 60-mg prasugrel or 600-mg clopidogrel but had not yet received any maintenance dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) at 6 Hours After the Loading Dose | 74.81 percent inhibition | Standard Deviation 13.01 |
| Clopidogrel | Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) at 6 Hours After the Loading Dose | 31.77 percent inhibition | Standard Deviation 21.07 |
p-value: <0.000195% CI: [38.04, 48.38]ANCOVA
Primary
Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate After 14 Days of Maintenance Dose Treatment
Measures IPA during maintenance dosing before and after cross-over for each therapy. IPA was defined as (1 - \[maximal platelet aggregation(MPA) at 14 days after study drug treatment\]/\[MPA before drug treatment\]) x 100.
Time frame: after 14 days of maintenance dosing
Population: Includes patients who received a loading dose and underwent percutaneous coronary intervention (PCI) regardless of GP IIb/IIIa antagonist use (this includes subjects who received prasugrel and clopidogrel, in either order, during crossover)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate After 14 Days of Maintenance Dose Treatment | 61.34 percent inhibition | Standard Deviation 17.84 |
| Clopidogrel | Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate After 14 Days of Maintenance Dose Treatment | 46.06 percent inhibition | Standard Deviation 21.34 |
p-value: <0.000195% CI: [10.6, 19.26]Mixed Models Analysis
Secondary
Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate at 2 Hours After the Loading Dose
IPA was defined as (1 - \[maximal platelet aggregation (MPA) at 2 hours after study drug treatment\]/\[MPA before drug treatment\]) x 100.
Time frame: 2 hours after loading dose
Population: Includes all patients who received a loading dose of study drug, did not receive a GP IIb/IIIa antagonist and had evaluable pretreatment and 2 hour MPA measurements. Patients had received a single loading dose of either 60-mg prasugrel or 600-mg clopidogrel but had not yet received any maintenance dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate at 2 Hours After the Loading Dose | 64.54 percent inhibition | Standard Deviation 20.43 |
| Clopidogrel | Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate at 2 Hours After the Loading Dose | 20.32 percent inhibition | Standard Deviation 20.22 |
p-value: <0.000195% CI: [38.35, 51.15]ANCOVA
Secondary
Myonecrosis Measure: Cardiac Troponin 18 to 24 Hours After the Loading Dose
Mean troponin level at 18 to 24 hours after the loading dose. Troponin is a biomarker for myonecrosis.
Time frame: 18 to 24 hours after loading dose
Population: Includes patients who received a loading dose, underwent PCI, did not receive a GP IIb/IIIa antagonist, and had an evaluable troponin measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Myonecrosis Measure: Cardiac Troponin 18 to 24 Hours After the Loading Dose | 0.12 ng/ml | Standard Deviation 0.273 |
| Clopidogrel | Myonecrosis Measure: Cardiac Troponin 18 to 24 Hours After the Loading Dose | 0.13 ng/ml | Standard Deviation 0.277 |
p-value: 0.452895% CI: [-0.25, 0.07]ANCOVA
Secondary
Myonecrosis Measure: Cardiac Troponin at 6 Hours After the Loading Dose
Mean troponin level at 6 hours after the loading dose. Troponin is a biomarker for myonecrosis.
Time frame: 6 hours after loading dose
Population: Includes patients who received a loading dose, underwent PCI, did not receive a GP IIb/IIIa antagonist, and had an evaluable troponin measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Myonecrosis Measure: Cardiac Troponin at 6 Hours After the Loading Dose | 0.06 ng/ml | Standard Deviation 0.204 |
| Clopidogrel | Myonecrosis Measure: Cardiac Troponin at 6 Hours After the Loading Dose | 0.05 ng/ml | Standard Deviation 0.128 |
p-value: 0.789395% CI: [-0.06, 0.08]ANCOVA
Secondary
Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) 18 to 24 Hours After the Loading Dose
Mean CK-MB at 18-24 hours after loading dose. CK-MB is a biomarker for myonecrosis.
Time frame: 18 to 24 hours after loading dose
Population: Includes patients who received a loading dose, underwent PCI, did not receive a GP IIb/IIIa antagonist, and had an evaluable CK-MB measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) 18 to 24 Hours After the Loading Dose | 11.64 IU/L | Standard Deviation 8.22 |
| Clopidogrel | Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) 18 to 24 Hours After the Loading Dose | 11.16 IU/L | Standard Deviation 8.72 |
p-value: 0.402995% CI: [-4.48, 1.82]ANCOVA
Secondary
Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) at 6 Hours After the Loading Dose
Mean CK-MB at 6 hours after loading dose. CK-MB is a biomarker for myonecrosis
Time frame: 6 hours after loading dose
Population: Includes patients who received a loading dose, underwent PCI, did not receive a GP IIb/IIIa antagonist, and had an evaluable CK-MB measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) at 6 Hours After the Loading Dose | 9.16 IU/L | Standard Deviation 8.3 |
| Clopidogrel | Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) at 6 Hours After the Loading Dose | 8.13 IU/L | Standard Deviation 5.16 |
p-value: 0.705895% CI: [-2.95, 2]ANCOVA
Secondary
Number of Hyporesponsive Participants at 6 Hours After the Loading Dose
Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20%
Time frame: 6 hours after loading dose
Population: Includes patients who received a loading dose of the study drug, did not receive a glycoprotein (GP) IIb/IIIa antagonist and had evaluable pre-treatment, and 6 hour MPA measurements.~Patients had received a single loading dose of either 60-mg prasugrel or 600-mg clopidogrel but had not yet received any maintenance dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Hyporesponsive Participants at 6 Hours After the Loading Dose | 0 participants |
| Clopidogrel | Number of Hyporesponsive Participants at 6 Hours After the Loading Dose | 21 participants |
p-value: <0.0001Chi-squared
Secondary
Number of Hyporesponsive Participants at the End of the Crossover Maintenance Dose Phase
Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20%
Time frame: 14 days after cross-over
Population: Includes patients who received a single loading dose and had evaluable MPA measures,regardless of glycoprotein (GP) IIb/IIIa antagonist use. Patients received 14 days of maintenance treatment and then crossed-over to the alternate maintenance treatment for 14 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Hyporesponsive Participants at the End of the Crossover Maintenance Dose Phase | 4 participants |
| Clopidogrel | Number of Hyporesponsive Participants at the End of the Crossover Maintenance Dose Phase | 1 participants |
p-value: 0.1827Fisher Exact
Secondary
Number of Hyporesponsive Participants at the End of the First Maintenance Dose Phase
Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) \<20%
Time frame: From loading dose to day 15
Population: Includes patients who received a single loading dose and had evaluable MPA measures, regardless of glycoprotein (GP) IIb/IIIa antagonist use. Patients had received 14 days of maintenance treatment but had not crossed-over to the alternate maintenance treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Hyporesponsive Participants at the End of the First Maintenance Dose Phase | 1 participants |
| Clopidogrel | Number of Hyporesponsive Participants at the End of the First Maintenance Dose Phase | 7 participants |
p-value: 0.0629Fisher Exact
Secondary
Number of Participants With Major Adverse Cardiac Events During the Crossover Maintenance Dose Phase
Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization
Time frame: 14 days after cross-over
Population: Includes all patients who received a loading dose and underwent PCI, received a maintenance dose for 14 days, and then crossed-over to the alternate therapy for an additional 14 days of maintenance dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Participants With Major Adverse Cardiac Events During the Crossover Maintenance Dose Phase | 1 participants |
| Clopidogrel | Number of Participants With Major Adverse Cardiac Events During the Crossover Maintenance Dose Phase | 0 participants |
Secondary
Number of Participants With Major Adverse Cardiac Events (MACE) During the First Maintenance Dose Phase
Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization
Time frame: after 14 days of treatment (before cross-over)
Population: Includes all patients who received a loading dose. Patients who underwent PCI also received 14 days of maintenance treatment. Patients had not yet crossed-over to the alternate maintenance treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Participants With Major Adverse Cardiac Events (MACE) During the First Maintenance Dose Phase | 2 participants |
| Clopidogrel | Number of Participants With Major Adverse Cardiac Events (MACE) During the First Maintenance Dose Phase | 1 participants |
Secondary
Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the Crossover Maintenance Dose Phase
Non-CABG-related TIMI major bleeding was any intracranial hemorrhage OR any clinically overt bleeding associated with a fall in hemoglobin \>=5 gm/dL. Non-CABG-related TIMI minor bleeding was any clinically overt bleeding associated with a fall in hemoglobin \>=3 gm/dL but \<5 gm/dL.
Time frame: 14 days after cross-over
Population: All patients who received a loading dose of study drug, received maintenance therapy for 14 days and then switched to the alternate maintenance therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the Crossover Maintenance Dose Phase | 0 participants |
| Clopidogrel | Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the Crossover Maintenance Dose Phase | 0 participants |
Secondary
Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the First Maintenance Dose Phase
Non-CABG-related TIMI major bleeding was any intracranial hemorrhage OR any clinically overt bleeding associated with a fall in hemoglobin \>=5 gm/dL. Non-CABG-related TIMI minor bleeding was any clinically overt bleeding associated with a fall in hemoglobin \>=3 gm/dL but \<5 gm/dL.
Time frame: after 14 days of treatment (before cross-over)
Population: Patients received a single loading dose and 14 days of maintenance therapy. Patients had not yet crossed-over to the alternate maintenance dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the First Maintenance Dose Phase | 2 participants |
| Clopidogrel | Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the First Maintenance Dose Phase | 0 participants |
Secondary
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) 18 to 24 Hours After the Loading Dose
VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean flourescence index. A lower PRI indicates greater antiplatelet effect.
Time frame: 18 to 24 hours after loading dose
Population: Includes patients who received a loading dose, underwent PCI, did not receive a GP IIb/IIIa antagonist, and had evaluable VASP measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) 18 to 24 Hours After the Loading Dose | 10.3 percent (%) platelet reactivity index | Standard Deviation 15.63 |
| Clopidogrel | Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) 18 to 24 Hours After the Loading Dose | 64.3 percent (%) platelet reactivity index | Standard Deviation 18.72 |
p-value: <0.000195% CI: [-63.2, -49.2]ANCOVA
Secondary
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) After 14 Days of Maintenance Dose Treatment
VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect.
Time frame: after 14 days of maintenance dosing
Population: Includes patients who received a loading dose and PCI, regardless of GP IIb/IIIa antagonist use (this includes subjects who received prasugrel and clopidogrel, in either order, during crossover)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) After 14 Days of Maintenance Dose Treatment | 23.4 percent (%) platelet reactivity index | Standard Deviation 19.19 |
| Clopidogrel | Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) After 14 Days of Maintenance Dose Treatment | 43.8 percent (%) platelet reactivity index | Standard Deviation 23.26 |
p-value: <0.000195% CI: [-25.7, -14.5]Mixed Models Analysis
Secondary
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 2 Hours After the Loading Dose
VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect.
Time frame: 2 hours after loading dose
Population: Includes patients who received a loading dose, underwent PCI, did not receive a GP IIb/IIIa antagonist, and had evaluable VASP measurements. Patients had received a single loading dose but had not yet received any maintenance treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 2 Hours After the Loading Dose | 21.5 percent (%) platelet reactivity index | Standard Deviation 27.06 |
| Clopidogrel | Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 2 Hours After the Loading Dose | 75.0 percent (%) platelet reactivity index | Standard Deviation 16.91 |
p-value: <0.000195% CI: [-61.2, -47.4]ANCOVA
Secondary
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 6 Hours After the Loading Dose
VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as \[(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100\] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect.
Time frame: 6 hours after loading dose
Population: Includes patients who received a loading dose, underwent PCI, and had evaluable VASP measurements, and did not receive a GP IIb/IIIa antagonist. Patients had received a single loading dose but had not yet received any maintenance treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 6 Hours After the Loading Dose | 7.4 percent (%) platelet reactivity index | Standard Deviation 16.66 |
| Clopidogrel | Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 6 Hours After the Loading Dose | 68.4 percent (%) platelet reactivity index | Standard Deviation 21.18 |
p-value: <0.000195% CI: [-67.1, -54]ANCOVA