Hypercholesterolemia, Acute Coronary Syndrome
Conditions
Brief summary
Primary Objective: To compare the efficacy of alirocumab (Praluent®) with standard of care (SoC) on coronary atheroma progression (percent change in normalized total atheroma volume \[TAV\]) after 9 months of treatment in participants who had acute coronary syndrome (ACS) within 4 weeks prior to randomization, with hypercholesterolemia treated with statin. Secondary Objectives: * To compare the efficacy of alirocumab (Praluent®) with SoC on secondary endpoints including absolute change in percent atheroma volume and normalized TAV after 9 months of treatment. * To evaluate the efficacy of alirocumab (Praluent®) on low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, triglycerides, non-high-density lipoprotein cholesterol and lipoprotein (a) after 9 months treatment. * To evaluate the safety of alirocumab (Praluent®) including the occurrence of cardiovascular events (coronary heart disease death, non-fatal myocardial infarction, fatal and non-fatal ischemic stroke, unstable angina requiring hospitalization) throughout the study.
Detailed description
The duration of study per participant was 9 months.
Interventions
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
DRUGAtorvastatin
Pharmaceutical form: tablet Route of administration: oral
DRUGRosuvastatin
Pharmaceutical form: tablet Route of administration: oral
DRUGFenofibrate
Pharmaceutical form: tablet Route of administration: oral
DRUGBezafibrate
Pharmaceutical form: tablet Route of administration: oral
DRUGEzetimibe
Pharmaceutical form: tablet Route of administration: oral
DRUGAntiplatelets
Pharmaceutical form: tablet or capsule Route of administration: oral
DRUGAnticoagulants
Pharmaceutical form: tablet or capsule Route of administration: oral
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Participants hospitalized for ACS (Acute ST-segment elevation myocardial infarction \[STEMI\], Acute non-ST-segment elevation myocardial infarction \[NSTEMI\], and unstable angina. * LDL-C \>=100 mg/dL at ACS diagnosis. * Participants who has stenosis with at least \>50% stenosis angiographically within 1 week after the ACS onset, and has analyzable coronary intravascular Ultrasound image. * Participants aged \>=20 years old at ACS diagnosis. * Negative Hepatitis B surface antigen, negative Hepatitis B core antibody, and negative Hepatitis C antibody. Or, negative Hepatitis B surface antigen, positive Hepatitis B core antibody, negative Hepatitis B deoxyribonucleic acid, and negative Hepatitis C antibody. * Written informed consent.
Exclusion criteria
* Participants who had previously treated with at least one dose of any anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibody. * Uncontrolled hypertension (multiple reading with systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) between ACS diagnosis and randomization visit. * Known history of hemorrhagic stroke. * Currently under treatment for cancer. * Participants on LDL apheresis. * Any clinically significant abnormality identified that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, participants with short life expectancy. * Considered by the Investigator or any sub-Investigator as inappropriate for this study for any reason, including: * Unable to meet specific protocol requirements, such as scheduled visits; * Investigator or any sub-Investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol, etc; * Presence of any other conditions (eg, geographic, social, etc.) actual or anticipated, that the Investigator feels would restrict or limit the participant's participation for the duration of the study. * Laboratory findings measured within 4 weeks after the ACS diagnosis (positive serum or urine pregnancy test in females of childbearing potential). The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at Week 36 | Baseline, Week 36 | Least-squares (LS) means and standard errors (SE) at Week 36 were obtained from analysis of covariance (ANCOVA) model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline normalized TAV as continuous fixed covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36 | Baseline, Week 36 | LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline normalized TAV as continuous fixed covariate. |
| Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at Week 36 | Baseline, Week 36 | Adjusted mean and SE at Week 36 were obtained from robust regression model with treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]), as fixed categorical effects, and the baseline EEM volume value as continuous fixed covariate. |
| Percent Change From Baseline in External Elastic Membrane Volume at Week 36 | Baseline, Week 36 | Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline EEM volume value as continuous fixed covariate. |
| Absolute Change From Baseline in Lumen Volume at Week 36 | Baseline, Week 36 | Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline lumen volume value as continuous fixed covariate. |
| Percent Change From Baseline in Lumen Volume at Week 36 | Baseline, Week 36 | Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effect, and the baseline lumen volume value as continuous fixed covariate. |
| Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Baseline, Week 12, Week 36 | Adjusted LS mean and SE at Week 12 and Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated LDL-C value and baseline calculated LDL-C value-by-time point interaction as continuous fixed covariates. |
| Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Baseline, Week 12, Week 36 | Adjusted LS mean and SE at Week 12 and Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated LDL-C value and baseline calculated LDL-C value-by-time point interaction as continuous fixed covariates. |
| Absolute Change From Baseline in Apolipoprotein B (Apo B) at Week 36 | Baseline, Week 36 | Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo B value as continuous fixed covariate. |
| Percent Change From Baseline in Apolipoprotein B at Week 36 | Baseline, Week 36 | Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo B value as continuous fixed covariate. |
| Absolute Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 36 | Baseline, Week 36 | Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated non-HDL-C value and baseline calculated non-HDL-C value-by-time point interaction as continuous fixed covariates. |
| Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol at Week 36 | Baseline, Week 36 | Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated non-HDL-C value and baseline calculated non-HDL-C value-by-time point interaction as continuous fixed covariates. |
| Absolute Change From Baseline in Percent Atheroma Volume (PAV) at Week 36 | Baseline, Week 36 | LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline PAV as continuous fixed covariate. |
| Percent Change From Baseline in Total Cholesterol at Week 36 | Baseline, Week 36 | Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline TC value and baseline TC value-by-time point interaction as continuous fixed covariates. |
| Absolute Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 36 | Baseline, Week 36 | Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effect, and baseline Lp(a) value as continuous fixed covariate. |
| Percent Change From Baseline in Lipoprotein (a) at Week 36 | Baseline, Week 36 | Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effect, and baseline Lp(a) value as continuous fixed covariate. |
| Absolute Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 | Baseline, Week 36 | Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline HDL-C value and baseline HDL-C value-by-time point interaction as continuous fixed covariates. |
| Percent Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 | Baseline, Week 36 | Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline HDL-C value and baseline HDL-C value-by-time point interaction as continuous fixed covariates. |
| Absolute Change From Baseline in Fasting Triglycerides (TGs) at Week 36 | Baseline, Week 36 | Adjusted mean and SE were obtained from multiple imputation approach followed by robust regression model including fixed categorical effect of treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) and the continuous fixed covariate of baseline fasting TGs value. |
| Percent Change From Baseline in Fasting Triglycerides at Week 36 | Baseline, Week 36 | Adjusted mean and SE were obtained by multiple imputation approach followed by robust regression model included fixed categorical effect of treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) and the continuous fixed covariate of baseline fasting TGs value. |
| Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 36 | Baseline, Week 36 | Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo A-1 value as continuous fixed covariate. |
| Percent Change From Baseline in Apolipoprotein A-1 at Week 36 | Baseline, Week 36 | Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo A-1 value as continuous fixed covariate. |
| Number of Participants With Cardiovascular (CV) Adverse Events | Up to 36 weeks | The suspected or confirmed CV events that occurred from randomization until end of the study visit were collected and reported. The various CV events included CV death, myocardial infarction, ischemic stroke, unstable angina requiring hospitalization , congestive heart failure requiring hospitalization, congestive heart failure requiring hospitalization, ischemia-driven coronary revascularization procedure. |
| Absolute Change From Baseline in Total Cholesterol (TC) at Week 36 | Baseline, Week 36 | LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated TC value and baseline calculated TC value-by-time point interaction as continuous fixed covariates. |
Countries
Japan
Participant flow
Recruitment details
The study was conducted at 39 active centers in Japan. Overall 214 participants were screened between 15 November 2016 and 02 November 2017, of whom 8 were screen failure and 206 were randomized to either alirocumab arm or standard of care (SoC) arm.
Pre-assignment details
Randomization was stratified by 'on statin therapy' or 'not on statin therapy' at the time of acute coronary syndrome (ACS) onset.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin \>=10 mg/day or rosuvastatin \>=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level \<100 mg/dL could not be achieved. | 102 |
| Alirocumab Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin \>=10 mg/day or rosuvastatin \>=5 mg/day). Statin (atorvastatin \>=10 mg/day or rosuvastatin \>=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was \>=100 mg/dL. | 104 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 |
| Overall Study | Poor Compliance to Protocol | 4 | 4 |
| Overall Study | Randomized but not treated | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Standard of Care | Alirocumab | Total |
|---|---|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 11.9 | 61.7 years STANDARD_DEVIATION 10.9 | 60.9 years STANDARD_DEVIATION 11.4 |
| Calculated LDL-C in mg/dL | 95.2 mg/dL STANDARD_DEVIATION 22.6 | 98.5 mg/dL STANDARD_DEVIATION 22.9 | 96.9 mg/dL STANDARD_DEVIATION 22.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 102 Participants | 104 Participants | 206 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 21 Participants | 40 Participants |
| Sex: Female, Male Male | 83 Participants | 83 Participants | 166 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 102 | 0 / 103 |
| other Total, other adverse events | 15 / 102 | 33 / 103 |
| serious Total, serious adverse events | 17 / 102 | 19 / 103 |
Outcome results
Primary
Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at Week 36
Least-squares (LS) means and standard errors (SE) at Week 36 were obtained from analysis of covariance (ANCOVA) model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline normalized TAV as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: Modified intent-to-treat (mITT) population: all participants who were allocated to a randomized treatment, recorded in the registration center database, had at least one dose or part of dose of study drug and had 2 analyzable normalized TAV values, 1 assessed before randomization, and one assessed after 24 weeks of treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at Week 36 | -3.14 percent change | Standard Error 0.97 |
| Alirocumab | Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at Week 36 | -4.79 percent change | Standard Error 0.95 |
Comparison: Analysis was performed using ANCOVA model which included fixed categorical effects of treatment arm and randomization strata, as well as the continuous fixed covariate of baseline normalized TAV.p-value: 0.227995% CI: [-4.32, 1.04]ANCOVA
Secondary
Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 36
Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo A-1 value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and one post-baseline Apo A-1 values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 36 | 3.8 mg/dL | Standard Error 1.9 |
| Alirocumab | Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 36 | 12.0 mg/dL | Standard Error 1.9 |
Secondary
Absolute Change From Baseline in Apolipoprotein B (Apo B) at Week 36
Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo B value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and one post-baseline Apo B values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Apolipoprotein B (Apo B) at Week 36 | -16.8 mg/dL | Standard Error 1.4 |
| Alirocumab | Absolute Change From Baseline in Apolipoprotein B (Apo B) at Week 36 | -51.0 mg/dL | Standard Error 1.3 |
Secondary
Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36
Adjusted LS mean and SE at Week 12 and Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated LDL-C value and baseline calculated LDL-C value-by-time point interaction as continuous fixed covariates.
Time frame: Baseline, Week 12, Week 36
Population: Participants of the mITT population with one baseline and at least one post-baseline calculated LDL-C values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Week 12 | -9.6 mg/dL | Standard Error 1.7 |
| Standard of Care | Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Week 36 | -15.5 mg/dL | Standard Error 1.8 |
| Alirocumab | Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Week 12 | -62.4 mg/dL | Standard Error 1.6 |
| Alirocumab | Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Week 36 | -63.2 mg/dL | Standard Error 1.8 |
Secondary
Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at Week 36
Adjusted mean and SE at Week 36 were obtained from robust regression model with treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]), as fixed categorical effects, and the baseline EEM volume value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at Week 36 | -8.23 mm^3 | Standard Error 1.85 |
| Alirocumab | Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at Week 36 | -10.01 mm^3 | Standard Error 1.81 |
Secondary
Absolute Change From Baseline in Fasting Triglycerides (TGs) at Week 36
Adjusted mean and SE were obtained from multiple imputation approach followed by robust regression model including fixed categorical effect of treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) and the continuous fixed covariate of baseline fasting TGs value.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and at least one post-baseline fasting TGs values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Fasting Triglycerides (TGs) at Week 36 | -26.2 mg/dL | Standard Error 4.7 |
| Alirocumab | Absolute Change From Baseline in Fasting Triglycerides (TGs) at Week 36 | -35.3 mg/dL | Standard Error 4.5 |
Secondary
Absolute Change From Baseline in High-density Lipoprotein Cholesterol at Week 36
Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline HDL-C value and baseline HDL-C value-by-time point interaction as continuous fixed covariates.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and at least one post-baseline HDL-C values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 | 4.7 mg/dL | Standard Error 0.9 |
| Alirocumab | Absolute Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 | 8.1 mg/dL | Standard Error 0.9 |
Secondary
Absolute Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 36
Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effect, and baseline Lp(a) value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and post-baseline Lp(a) values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 36 | -10.3 mg/dL | Standard Error 0.5 |
| Alirocumab | Absolute Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 36 | -15.5 mg/dL | Standard Error 0.5 |
Secondary
Absolute Change From Baseline in Lumen Volume at Week 36
Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline lumen volume value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Lumen Volume at Week 36 | -1.25 mm^3 | Standard Error 1.38 |
| Alirocumab | Absolute Change From Baseline in Lumen Volume at Week 36 | -0.93 mm^3 | Standard Error 1.35 |
Secondary
Absolute Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 36
Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated non-HDL-C value and baseline calculated non-HDL-C value-by-time point interaction as continuous fixed covariates.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 36 | -20.3 mg/dL | Standard Error 2 |
| Alirocumab | Absolute Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 36 | -69.2 mg/dL | Standard Error 2 |
Secondary
Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36
LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline normalized TAV as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36 | -4.73 cubic millimeter (mm^3) | Standard Error 1.02 |
| Alirocumab | Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36 | -5.77 cubic millimeter (mm^3) | Standard Error 1 |
Secondary
Absolute Change From Baseline in Percent Atheroma Volume (PAV) at Week 36
LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline PAV as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Percent Atheroma Volume (PAV) at Week 36 | -1.28 percent atheroma volume | Standard Error 0.39 |
| Alirocumab | Absolute Change From Baseline in Percent Atheroma Volume (PAV) at Week 36 | -1.42 percent atheroma volume | Standard Error 0.38 |
Secondary
Absolute Change From Baseline in Total Cholesterol (TC) at Week 36
LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated TC value and baseline calculated TC value-by-time point interaction as continuous fixed covariates.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and at least one post-baseline TC values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change From Baseline in Total Cholesterol (TC) at Week 36 | -15.2 mg/dL | Standard Error 2.3 |
| Alirocumab | Absolute Change From Baseline in Total Cholesterol (TC) at Week 36 | -61.7 mg/dL | Standard Error 2.2 |
Secondary
Number of Participants With Cardiovascular (CV) Adverse Events
The suspected or confirmed CV events that occurred from randomization until end of the study visit were collected and reported. The various CV events included CV death, myocardial infarction, ischemic stroke, unstable angina requiring hospitalization , congestive heart failure requiring hospitalization, congestive heart failure requiring hospitalization, ischemia-driven coronary revascularization procedure.
Time frame: Up to 36 weeks
Population: Safety population: all participants who actually received at least 1 dose or part of a dose of the study drug, and analyzed according to the treatment actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care | Number of Participants With Cardiovascular (CV) Adverse Events | Cardiovascular death | 0 Participants |
| Standard of Care | Number of Participants With Cardiovascular (CV) Adverse Events | Myocardial infarction | 3 Participants |
| Standard of Care | Number of Participants With Cardiovascular (CV) Adverse Events | Ischemic stroke | 0 Participants |
| Standard of Care | Number of Participants With Cardiovascular (CV) Adverse Events | Unstable angina requiring hospitalization | 0 Participants |
| Standard of Care | Number of Participants With Cardiovascular (CV) Adverse Events | Congestive heart failure requiring hospitalization | 0 Participants |
| Standard of Care | Number of Participants With Cardiovascular (CV) Adverse Events | Ischemia led coronary revascularization procedure | 2 Participants |
| Alirocumab | Number of Participants With Cardiovascular (CV) Adverse Events | Congestive heart failure requiring hospitalization | 0 Participants |
| Alirocumab | Number of Participants With Cardiovascular (CV) Adverse Events | Cardiovascular death | 0 Participants |
| Alirocumab | Number of Participants With Cardiovascular (CV) Adverse Events | Unstable angina requiring hospitalization | 0 Participants |
| Alirocumab | Number of Participants With Cardiovascular (CV) Adverse Events | Myocardial infarction | 2 Participants |
| Alirocumab | Number of Participants With Cardiovascular (CV) Adverse Events | Ischemia led coronary revascularization procedure | 4 Participants |
| Alirocumab | Number of Participants With Cardiovascular (CV) Adverse Events | Ischemic stroke | 2 Participants |
Secondary
Percent Change From Baseline in Apolipoprotein A-1 at Week 36
Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo A-1 value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and one post-baseline Apo A-1 values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in Apolipoprotein A-1 at Week 36 | 4.61 percent change | Standard Error 1.62 |
| Alirocumab | Percent Change From Baseline in Apolipoprotein A-1 at Week 36 | 11.75 percent change | Standard Error 1.58 |
Secondary
Percent Change From Baseline in Apolipoprotein B at Week 36
Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and baseline Apo B value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and one post-baseline Apo B values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in Apolipoprotein B at Week 36 | -16.61 percent change | Standard Error 1.56 |
| Alirocumab | Percent Change From Baseline in Apolipoprotein B at Week 36 | -55.13 percent change | Standard Error 1.53 |
Secondary
Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36
Adjusted LS mean and SE at Week 12 and Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated LDL-C value and baseline calculated LDL-C value-by-time point interaction as continuous fixed covariates.
Time frame: Baseline, Week 12, Week 36
Population: mITT population with one baseline and at least one post-baseline calculated LDL-C values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care | Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Week 12 | -7.57 percent change | Standard Error 1.91 |
| Standard of Care | Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Week 36 | -13.40 percent change | Standard Error 1.99 |
| Alirocumab | Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Week 12 | -64.53 percent change | Standard Error 1.83 |
| Alirocumab | Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 | Week 36 | -63.94 percent change | Standard Error 1.91 |
Secondary
Percent Change From Baseline in External Elastic Membrane Volume at Week 36
Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline EEM volume value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in External Elastic Membrane Volume at Week 36 | -0.86 percent change | Standard Error 0.93 |
| Alirocumab | Percent Change From Baseline in External Elastic Membrane Volume at Week 36 | -3.18 percent change | Standard Error 0.91 |
Secondary
Percent Change From Baseline in Fasting Triglycerides at Week 36
Adjusted mean and SE were obtained by multiple imputation approach followed by robust regression model included fixed categorical effect of treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) and the continuous fixed covariate of baseline fasting TGs value.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and at least one post-baseline fasting TGs values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in Fasting Triglycerides at Week 36 | -8.85 percent change | Standard Error 3.62 |
| Alirocumab | Percent Change From Baseline in Fasting Triglycerides at Week 36 | -18.37 percent change | Standard Error 3.51 |
Secondary
Percent Change From Baseline in High-density Lipoprotein Cholesterol at Week 36
Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline HDL-C value and baseline HDL-C value-by-time point interaction as continuous fixed covariates.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and at least one post-baseline HDL-C values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 | 12.19 percent change | Standard Error 2.3 |
| Alirocumab | Percent Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 | 21.04 percent change | Standard Error 2.25 |
Secondary
Percent Change From Baseline in Lipoprotein (a) at Week 36
Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effect, and baseline Lp(a) value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and one post-baseline Lp(a) values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in Lipoprotein (a) at Week 36 | -17.23 percent change | Standard Error 2.6 |
| Alirocumab | Percent Change From Baseline in Lipoprotein (a) at Week 36 | -55.76 percent change | Standard Error 2.54 |
Secondary
Percent Change From Baseline in Lumen Volume at Week 36
Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effect, and the baseline lumen volume value as continuous fixed covariate.
Time frame: Baseline, Week 36
Population: mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in Lumen Volume at Week 36 | 1.20 percent change | Standard Error 1.26 |
| Alirocumab | Percent Change From Baseline in Lumen Volume at Week 36 | -0.86 percent change | Standard Error 1.23 |
Secondary
Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol at Week 36
Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated non-HDL-C value and baseline calculated non-HDL-C value-by-time point interaction as continuous fixed covariates.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol at Week 36 | -14.06 percent change | Standard Error 1.71 |
| Alirocumab | Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol at Week 36 | -54.50 percent change | Standard Error 1.67 |
Secondary
Percent Change From Baseline in Total Cholesterol at Week 36
Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset \[Yes / No\]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline TC value and baseline TC value-by-time point interaction as continuous fixed covariates.
Time frame: Baseline, Week 36
Population: Participants of the mITT population with one baseline and at least one post-baseline TC values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change From Baseline in Total Cholesterol at Week 36 | -7.59 percent change | Standard Error 1.35 |
| Alirocumab | Percent Change From Baseline in Total Cholesterol at Week 36 | -35.43 percent change | Standard Error 1.32 |