Acute Coronary Syndrome
Conditions
Keywords
Atherosclerosis, Heart disease, Cardiovascular disease, Lp-PLA2 inhibitor, The TIMI Study Group, Coronary Heart Disease (CHD), Acute Coronary Syndrome (ACS)
Brief summary
This study will test whether darapladib can safely lower the chances of having a cardiovascular event (such as a heart attack or urgent coronary revascularization (e.g. medical procedures performed to restore the normal blood flow in patients with atherosclerosis)) when treatment is started within 30 days after an acute coronary syndrome (also called ACS).
Detailed description
Subjects who qualify for the study will be randomized 1:1 to either darapladib or placebo administered in addition to standard therapy. Following the baseline visit, subjects will be expected to return for clinic visits at 1 month, 3 months, 6 months and every 6 months until the end of the study.
Interventions
Lp-PLA2 inhibitor
DRUGPlacebo
Placebo administered
OTHERStandard Therapy
Guideline mandated therapy for individual's condition
Sponsors
The TIMI Study Group
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
* Signed written informed consent. * Men or women at least 18 years old (in Taiwan, at least 20 years old). Women must be post-menopausal or using a highly effective method for avoidance of pregnancy. * Hospitalization for acute coronary syndrome (ACS) within 30 days prior to study entry. * Clinically stable for 24 hours prior to study entry. * A planned percutaneous coronary intervention (PCI) should be performed prior to study entry, whenever possible. * At least one of the following: * At least 60 years old. * Myocardial infarction prior to the qualifying ACS event. * Diabetes mellitus requiring treatment with medication. * Diagnosed mild or moderate reduction in kidney function. * Cerebrovascular disease (carotid artery disease or ischemic stroke more than 3 months prior to study entry) OR peripheral artery disease.
Exclusion criteria
* ACS symptoms or lab results not believed to be caused by a narrowing or blocked coronary artery. * No major coronary artery with a blockage of more than 50% (unless all stenoses are successfully treated by PCI). * Planned coronary artery bypass graft (CABG) surgery, or CABG surgery performed after the qualifying ACS event and prior to study entry. * Certain types of liver disease. * Severe reduction in kidney function OR removal of a kidney OR kidney transplant. * Severe heart failure. * Blood pressure higher than normal despite lifestyle changes and treatment with medications. * Any life-threatening disease with a life expectancy of less than 2 years (other than heart disease) that may prevent the subject from completing the study. * Severe asthma that is poorly controlled with medication. * Pregnancy (Note: A pregnancy test will be performed on all non-sterile women prior to study entry). * Previous severe allergic reaction to food, medications, drink, insect stings, etc. * Drug or alcohol abuse within the past 6 months. Mental/psychological impairment that may prevent the subject from complying with study procedures or understanding the goal and potential risks of participating in the study. * Certain medications that may interfere with the study medication (these will be identified by the study doctor). * If both birth parents are at least 50% Japanese, Chinese, or Korean ancestry, must have a blood sample collected for Lp-PLA2 activity. Those with Lp-PLA2 activity less than or equal to 20.0 nmol/min/mL are excluded. * Previously took darapladib (SB-480848). * Participation in a study of an investigational medication within the past 30 days. * Current participation in a study of an investigational device. * Any other reason the investigator deems the subject should not participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Occurrence of Any Event in the Composite of Major Coronary Events During the Time Period for Follow-up (FU) of Cardiovascular (CV) Event | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | Coronary heart disease (CHD) death=occurrence of a fatal myocardial infarction (MI), death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a nonischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Urgent coronary revascularization (CR) for MI=ischemic discomfort at rest that prompted CR during the same hospitalization or resulted in hospital transfer for the purpose of CR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Cardiovascular Death During the Time Period for Follow-up of Cardiovascular Events | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | CV death is defined as a death due to a CV cause, which includes but is not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths. |
| Number of Participants With First Occurrence of MI (Fatal/Nonfatal) During the Time Period for Follow-up of Cardiovascular Events | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. |
| Number of Participants With First Occurrence of Stroke (Fatal/Non-fatal) During the Time Period for Follow-up of Cardiovascular Events | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | Stroke is defined as the presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting \>24 hours or results in death (in \<24 hours). |
| Number of Participants With CHD Death During the Time Period for Follow-up of Cardiovascular Events | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | CHD death is defined as the occurrence of a fatal MI, death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death. |
| Number of Participants With Urgent Coronary Revascularization for Myocardial Ischemia During the Time Period for Follow-up of Cardiovascular Events | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | Urgent coronary revascularization for myocardial ischemia is defined as ischemic discomfort at rest that prompts coronary revascularization (PCI or coronary artery bypass graft \[CABG\]) during the same hospitalization or resulting in hospital transfer for the purpose of coronary revascularization. PCI is defined as any attempt at revascularization even if not successful (e.g., angioplasty, atherectomy or stenting). |
| Number of Participants With First Occurrence of Any Component of the Composite of Major Adverse Cardiovascular Events (Cardiovascular [CV] Death, Non-fatal MI or Non-fatal Stroke) During the Time Period for Follow-up of CV Events | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | CV death=death due to a CV cause, which included but was not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting \>24 hours or results in death (in \<24 hours). |
| Number of Participants With First Occurrence of Any Coronary Revascularization Procedures (Excluding Coronary Revascularization Planned Prior to Randomization, But Performed After Randomization) During the Time Period for Follow-up of Cardiovascular Event | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | All coronary revascularization procedures (except for PCI planned prior to randomization but performed after randomization) are included. Examples include coronary artery bypass graft, balloon angioplasty and stenting. The number of participants, with first occurrence of any coronary revascularization procedures, were reported. |
| Number of Participants With First Occurrence of Any Component of the Composite of All-cause Mortality, Non-fatal MI, or Nonfatal Stroke During the Time Period for Follow-up of Cardiovascular Events | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting \>24 hours or results in death (in \<24 hours). |
| Number of Participants With First Occurrence of Any Event in the Composite of CHD Death and Non-fatal MI During the Time Period for Follow-up of Cardiovascular Events | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. CHD death is defined as the occurrence of a fatal MI, death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death. |
| Number of Participants With All-cause Mortality During the Time Period for Vital Status | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | Number of participants who died, during the vital status time-period were reported. The participants who were known to have died, date of death was used; for participants who completed the study the study completion date was used; for participants who withdrew from the study where vital status was ascertained , and are known to have not died , the last known date to be alive was used and for participants whom vital status was not ascertained, following study withdrawal the study withdrawal date was used. |
| Number of Participants With First Occurrence of Any Event in the Composite of Total Coronary Events (CHD Death, Non-fatal MI, Hospitalization for Unstable Angina, or Any Coronary Revascularization Procedure) During the Time Period for FU of CV Events | From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) | CHD death, acute MI, and prior MI diagnosed post-randomization are defined in the primary endpoint (major coronary events). Hospitalization for unstable angina=one of the following, but not fulfilling the criteria for MI: ischemic discomfort at rest associated with electrocardiogram (ECG) changes leading to hospitalization; ischemic discomfort at rest regardless of ECG changes leading to hospitalization and revascularization during the same admission; ischemic discomfort at rest in hospital associated with ECG changes; ischemic discomfort at rest in hospital without ECG changes resulting in revascularization during the same admission. NOTE: The event was not considered to be unstable angina if, after invasive/non-invasive testing or other diagnostic testing, the discomfort was found not to be caused by myocardial ischemia. Coronary revascularization procedures exclude PCI planned prior to randomization but performed after randomization. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Netherlands, New Zealand, Peru, Philippines, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 868 centers in 36 countries: North America (282), Western Europe (210), Eastern Europe (166), Asia/Pacific (127), South America (83) during 07 December 2009 to 24 April 2014. A total of 13026 participants were randomized to the study.
Pre-assignment details
During the screening phase of the study, participants presenting with acute coronary syndrome (ACS) were randomized within 30 days. Approximately 77% of participants underwent percutaneous coronary intervention (PCI) for the qualifying event.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants were randomized to receive matching placebo once daily. | 6,522 |
| Darapladib 160 mg Participants were randomized to receive darapladib 160 mg enteric-coated tablets once daily. | 6,504 |
| Total | 13,026 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 41 | 43 |
| Overall Study | Study closed/terminated | 23 | 24 |
| Overall Study | Withdrawal by Subject | 111 | 109 |
Baseline characteristics
| Characteristic | Placebo | Darapladib 160 mg | Total |
|---|---|---|---|
| Age, Continuous | 64.3 Years STANDARD_DEVIATION 9.5 | 64.1 Years STANDARD_DEVIATION 9.52 | 64.2 Years STANDARD_DEVIATION 9.51 |
| Race/Ethnicity, Customized African American/African Heritage | 160 Participants | 155 Participants | 315 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 56 Participants | 52 Participants | 108 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 200 Participants | 211 Participants | 411 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 351 Participants | 349 Participants | 700 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 109 Participants | 109 Participants | 218 Participants |
| Race/Ethnicity, Customized Asian - Mixed Race | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 123 Participants | 116 Participants | 239 Participants |
| Race/Ethnicity, Customized Mixed Race | 43 Participants | 52 Participants | 95 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 9 Participants | 5 Participants | 14 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 138 Participants | 119 Participants | 257 Participants |
| Race/Ethnicity, Customized White - Mixed Race | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 5329 Participants | 5331 Participants | 10660 Participants |
| Sex: Female, Male Female | 1669 Participants | 1657 Participants | 3326 Participants |
| Sex: Female, Male Male | 4853 Participants | 4847 Participants | 9700 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 403 / 6,465 | 376 / 6,452 |
| other Total, other adverse events | 3,416 / 6,465 | 3,698 / 6,452 |
| serious Total, serious adverse events | 3,011 / 6,465 | 2,933 / 6,452 |
Outcome results
Primary
Number of Participants With First Occurrence of Any Event in the Composite of Major Coronary Events During the Time Period for Follow-up (FU) of Cardiovascular (CV) Event
Coronary heart disease (CHD) death=occurrence of a fatal myocardial infarction (MI), death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a nonischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Urgent coronary revascularization (CR) for MI=ischemic discomfort at rest that prompted CR during the same hospitalization or resulted in hospital transfer for the purpose of CR.
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized intent-to-treat (ITT) Population consisted of all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With First Occurrence of Any Event in the Composite of Major Coronary Events During the Time Period for Follow-up (FU) of Cardiovascular (CV) Event | 910 Participants |
| Darapladib 160 mg | Number of Participants With First Occurrence of Any Event in the Composite of Major Coronary Events During the Time Period for Follow-up (FU) of Cardiovascular (CV) Event | 903 Participants |
p-value: 0.92995.02% CI: [0.91, 1.09]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With All-cause Mortality During the Time Period for Vital Status
Number of participants who died, during the vital status time-period were reported. The participants who were known to have died, date of death was used; for participants who completed the study the study completion date was used; for participants who withdrew from the study where vital status was ascertained , and are known to have not died , the last known date to be alive was used and for participants whom vital status was not ascertained, following study withdrawal the study withdrawal date was used.
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With All-cause Mortality During the Time Period for Vital Status | 403 Participants |
| Darapladib 160 mg | Number of Participants With All-cause Mortality During the Time Period for Vital Status | 376 Participants |
p-value: 0.36295% CI: [0.81, 1.08]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With Cardiovascular Death During the Time Period for Follow-up of Cardiovascular Events
CV death is defined as a death due to a CV cause, which includes but is not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths.
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Cardiovascular Death During the Time Period for Follow-up of Cardiovascular Events | 268 Participants |
| Darapladib 160 mg | Number of Participants With Cardiovascular Death During the Time Period for Follow-up of Cardiovascular Events | 243 Participants |
p-value: 0.27495% CI: [0.76, 1.08]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With CHD Death During the Time Period for Follow-up of Cardiovascular Events
CHD death is defined as the occurrence of a fatal MI, death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death.
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With CHD Death During the Time Period for Follow-up of Cardiovascular Events | 241 Participants |
| Darapladib 160 mg | Number of Participants With CHD Death During the Time Period for Follow-up of Cardiovascular Events | 211 Participants |
p-value: 0.16195% CI: [0.73, 1.05]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With First Occurrence of Any Component of the Composite of All-cause Mortality, Non-fatal MI, or Nonfatal Stroke During the Time Period for Follow-up of Cardiovascular Events
Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting \>24 hours or results in death (in \<24 hours).
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With First Occurrence of Any Component of the Composite of All-cause Mortality, Non-fatal MI, or Nonfatal Stroke During the Time Period for Follow-up of Cardiovascular Events | 928 Participants |
| Darapladib 160 mg | Number of Participants With First Occurrence of Any Component of the Composite of All-cause Mortality, Non-fatal MI, or Nonfatal Stroke During the Time Period for Follow-up of Cardiovascular Events | 914 Participants |
p-value: 0.79795% CI: [0.9, 1.08]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With First Occurrence of Any Component of the Composite of Major Adverse Cardiovascular Events (Cardiovascular [CV] Death, Non-fatal MI or Non-fatal Stroke) During the Time Period for Follow-up of CV Events
CV death=death due to a CV cause, which included but was not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting \>24 hours or results in death (in \<24 hours).
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With First Occurrence of Any Component of the Composite of Major Adverse Cardiovascular Events (Cardiovascular [CV] Death, Non-fatal MI or Non-fatal Stroke) During the Time Period for Follow-up of CV Events | 838 Participants |
| Darapladib 160 mg | Number of Participants With First Occurrence of Any Component of the Composite of Major Adverse Cardiovascular Events (Cardiovascular [CV] Death, Non-fatal MI or Non-fatal Stroke) During the Time Period for Follow-up of CV Events | 824 Participants |
p-value: 0.77795.02% CI: [0.9, 1.09]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With First Occurrence of Any Coronary Revascularization Procedures (Excluding Coronary Revascularization Planned Prior to Randomization, But Performed After Randomization) During the Time Period for Follow-up of Cardiovascular Event
All coronary revascularization procedures (except for PCI planned prior to randomization but performed after randomization) are included. Examples include coronary artery bypass graft, balloon angioplasty and stenting. The number of participants, with first occurrence of any coronary revascularization procedures, were reported.
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With First Occurrence of Any Coronary Revascularization Procedures (Excluding Coronary Revascularization Planned Prior to Randomization, But Performed After Randomization) During the Time Period for Follow-up of Cardiovascular Event | 967 Participants |
| Darapladib 160 mg | Number of Participants With First Occurrence of Any Coronary Revascularization Procedures (Excluding Coronary Revascularization Planned Prior to Randomization, But Performed After Randomization) During the Time Period for Follow-up of Cardiovascular Event | 926 Participants |
p-value: 0.32995% CI: [0.87, 1.05]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With First Occurrence of Any Event in the Composite of CHD Death and Non-fatal MI During the Time Period for Follow-up of Cardiovascular Events
Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. CHD death is defined as the occurrence of a fatal MI, death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death.
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With First Occurrence of Any Event in the Composite of CHD Death and Non-fatal MI During the Time Period for Follow-up of Cardiovascular Events | 725 Participants |
| Darapladib 160 mg | Number of Participants With First Occurrence of Any Event in the Composite of CHD Death and Non-fatal MI During the Time Period for Follow-up of Cardiovascular Events | 701 Participants |
p-value: 0.54695% CI: [0.87, 1.07]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With First Occurrence of Any Event in the Composite of Total Coronary Events (CHD Death, Non-fatal MI, Hospitalization for Unstable Angina, or Any Coronary Revascularization Procedure) During the Time Period for FU of CV Events
CHD death, acute MI, and prior MI diagnosed post-randomization are defined in the primary endpoint (major coronary events). Hospitalization for unstable angina=one of the following, but not fulfilling the criteria for MI: ischemic discomfort at rest associated with electrocardiogram (ECG) changes leading to hospitalization; ischemic discomfort at rest regardless of ECG changes leading to hospitalization and revascularization during the same admission; ischemic discomfort at rest in hospital associated with ECG changes; ischemic discomfort at rest in hospital without ECG changes resulting in revascularization during the same admission. NOTE: The event was not considered to be unstable angina if, after invasive/non-invasive testing or other diagnostic testing, the discomfort was found not to be caused by myocardial ischemia. Coronary revascularization procedures exclude PCI planned prior to randomization but performed after randomization.
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With First Occurrence of Any Event in the Composite of Total Coronary Events (CHD Death, Non-fatal MI, Hospitalization for Unstable Angina, or Any Coronary Revascularization Procedure) During the Time Period for FU of CV Events | 1352 Participants |
| Darapladib 160 mg | Number of Participants With First Occurrence of Any Event in the Composite of Total Coronary Events (CHD Death, Non-fatal MI, Hospitalization for Unstable Angina, or Any Coronary Revascularization Procedure) During the Time Period for FU of CV Events | 1290 Participants |
p-value: 0.20295% CI: [0.88, 1.03]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With First Occurrence of MI (Fatal/Nonfatal) During the Time Period for Follow-up of Cardiovascular Events
Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI.
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With First Occurrence of MI (Fatal/Nonfatal) During the Time Period for Follow-up of Cardiovascular Events | 564 Participants |
| Darapladib 160 mg | Number of Participants With First Occurrence of MI (Fatal/Nonfatal) During the Time Period for Follow-up of Cardiovascular Events | 547 Participants |
p-value: 0.63195% CI: [0.86, 1.09]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With First Occurrence of Stroke (Fatal/Non-fatal) During the Time Period for Follow-up of Cardiovascular Events
Stroke is defined as the presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting \>24 hours or results in death (in \<24 hours).
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With First Occurrence of Stroke (Fatal/Non-fatal) During the Time Period for Follow-up of Cardiovascular Events | 130 Participants |
| Darapladib 160 mg | Number of Participants With First Occurrence of Stroke (Fatal/Non-fatal) During the Time Period for Follow-up of Cardiovascular Events | 145 Participants |
p-value: 0.35495% CI: [0.88, 1.42]Cox Proportional Hazard Regression Model
Secondary
Number of Participants With Urgent Coronary Revascularization for Myocardial Ischemia During the Time Period for Follow-up of Cardiovascular Events
Urgent coronary revascularization for myocardial ischemia is defined as ischemic discomfort at rest that prompts coronary revascularization (PCI or coronary artery bypass graft \[CABG\]) during the same hospitalization or resulting in hospital transfer for the purpose of coronary revascularization. PCI is defined as any attempt at revascularization even if not successful (e.g., angioplasty, atherectomy or stenting).
Time frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years)
Population: All-Randomized ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Urgent Coronary Revascularization for Myocardial Ischemia During the Time Period for Follow-up of Cardiovascular Events | 218 Participants |
| Darapladib 160 mg | Number of Participants With Urgent Coronary Revascularization for Myocardial Ischemia During the Time Period for Follow-up of Cardiovascular Events | 237 Participants |
p-value: 0.3695% CI: [0.91, 1.31]Cox Proportional Hazard Regression Model