Acute Coronary Syndrome
Conditions
Keywords
Asia Lipitor Pre-treatment in Acute Coronary Syndrome
Brief summary
This present study is specifically designed to examine the efficacy and safety of a high pre-treatment dose of atorvastatin in Asian patients with NSTE-ACS in China and the Republic of Korea, by using a treatment paradigm similar to that employed in the ARMYDA-ACS study.
Interventions
DRUGAtorvastatin
80mg 12 hours pre-Percutaneous Coronary Intervention (PCI), 40mg 2 hours pre-PCI and 40mg daily after PCI for 30 days.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Non-ST elevated ACS; LDL-C \> 80 mg/dl
Exclusion criteria
* ST elevated acute myocardial infarction; previously or currently treated with atorvastatin or other statins
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI) | 30 days post PCI | Percentage calculated as: (number of participants who experienced MACE \[death, myocardial infarction, target vessel revascularization\] within 30 days post-PCI) divided by (number of participants who experienced PCI) \* 100. Major Adverse Cardiac Events (MACE) that occurred after 33 days post PCI were excluded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 24 Hours Post-PCI | 24 hours post PCI | Percentage calculated as: (number of participants who experienced MACE within 24 hours post PCI) divided by (number of participants who experienced PCI) \* 100. |
| Percentage of Participants With Elevated Creatine Kinase-MB (CK-MB) | 8 hours, 24 hours and 30 days post PCI | CK-MB above the upper limit of normal range from baseline (biomarker of myocardial injury); normal range: 0-5.0 nanograms per milliliter (ng/mL). |
| Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 8 Hours Post-PCI | 8 hours post PCI | Percentage calculated as: (number of participants who experienced MACE within 8 hours post-PCI) divided by (number of participants who experienced PCI) \* 100. |
| Percentage of Participants With Elevated Myoglobin | 8 hours, 24 hours and 30 days post PCI | Myoglobin above the upper limit of normal from baseline (biomarker of myocardial injury): normal range: 0-109 nanograms per milliliter (ng/mL). |
| Percent Change From Baseline in C-Reactive Protein (CRP) | Baseline, 8 hours, 24 hours and 30 days | C-reactive protein percent change from baseline = (post baseline value minus baseline value) divided by baseline value\*100. Includes all CRP samples tested for the study, including samples unaffected and those samples affected by defective high-sensitivity (hs) CRP reagents. |
| Percentage of Participants With Elevated Troponin I | 8 hours, 24 hours and 30 days post PCI | Troponin I above the upper limit of normal range from baseline (biomarker of myocardial injury): normal range: 0-0.5 nanograms per milliliter (ng/mL). |
Countries
China, South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin Atorvastatin 80 mg 12 hours pre- percutaneous coronary intervention (PCI) and 40 mg 2 hours PCI, and usual care. | 247 |
| Usual Care Aspirin 200-300 mg pre-PCI and 100-200 mg daily thereafter; clopidogrel 300 mg loading dose at least 3 hours pre-PCI and 75 mg thereafter; subcutaneous heparin: enoxaparin 1 mg/kg every 12 hours pre-PCI or dalteparin 120 IU/kg every 12 hours pre-PCI; and atorvastatin 40 mg daily after PCI for 30 days. | 252 |
| Total | 499 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Not Treated | 2 | 2 |
| Overall Study | Other | 85 | 77 |
| Overall Study | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Atorvastatin | Usual Care | Total |
|---|---|---|---|
| Age, Customized 18 to 44 years | 23 participants | 9 participants | 32 participants |
| Age, Customized 45 to 64 years | 134 participants | 156 participants | 290 participants |
| Age, Customized >= 65 years | 90 participants | 87 participants | 177 participants |
| Sex: Female, Male Female | 81 Participants | 77 Participants | 158 Participants |
| Sex: Female, Male Male | 166 Participants | 175 Participants | 341 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 65 / 245 | 45 / 250 |
| serious Total, serious adverse events | 16 / 245 | 16 / 250 |
Outcome results
Primary
Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI)
Percentage calculated as: (number of participants who experienced MACE \[death, myocardial infarction, target vessel revascularization\] within 30 days post-PCI) divided by (number of participants who experienced PCI) \* 100. Major Adverse Cardiac Events (MACE) that occurred after 33 days post PCI were excluded.
Time frame: 30 days post PCI
Population: Full Analysis Set (FAS): all participants who received at least one dose of study medication and received percutaneous coronary intervention (PCI). Last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atorvastatin | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI) | Myocardial Infarction | 14.1 percentage of participants |
| Atorvastatin | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI) | Death | 0.6 percentage of participants |
| Atorvastatin | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI) | Target Vessel Revascularization | 0.0 percentage of participants |
| Atorvastatin | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI) | Total MACE | 14.7 percentage of participants |
| Usual Care | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI) | Death | 0.6 percentage of participants |
| Usual Care | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI) | Total MACE | 15.7 percentage of participants |
| Usual Care | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI) | Target Vessel Revascularization | 0.0 percentage of participants |
| Usual Care | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 30 Days Post-percutaneous Coronary Intervention (PCI) | Myocardial Infarction | 15.1 percentage of participants |
Comparison: Total MACE: treatment difference. Null hypothesis = no difference between the incidence rates in the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 0.923795% CI: [-7.3, 9.3]Chi-squared, Corrected
Comparison: Death: treatment difference. Null hypothesis = no difference between the incidence rates in two groups. Fisher's exact test was applied because the expected frequency of events was less than 5.p-value: 195% CI: [-10.7, 10.7]Fisher Exact
Comparison: Myocardial Infarction: treatment difference. Null hypothesis = no difference between the incidence rates in the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 0.915895% CI: [-7.2, 9.2]Chi-squared, Corrected
Comparison: Unadjusted odds ratio and 95% confidence interval calculated by including treatment group as the only covariate in the logistic regression model. Reference group = usual care.p-value: 0.895% CI: [0.5104, 1.6846]Regression, Logistic
Comparison: Adjusted odds ratio: model includes treatment group and potential confounding covariates age, gender, country, non-ST elevation myocardial infarction, LVEF \<=40, and use of beta-blockers, ACE-inhibitors, angiotension receptor blockers, calcium channel antagonists, and diuretics. Reference group = usual care.p-value: 0.995% CI: [0.4887, 1.8836]Regression, Logistic
Comparison: MACE-free survival up to Day 30. A censoring variable with a value of 1 denoted that the subject had the event and 0 indicated that the subject was censored. A log-rank test was applied to investigate any differences on the survival distribution function between two treatment groups.p-value: 0.8494Log Rank
Secondary
Percentage of Participants With Elevated Creatine Kinase-MB (CK-MB)
CK-MB above the upper limit of normal range from baseline (biomarker of myocardial injury); normal range: 0-5.0 nanograms per milliliter (ng/mL).
Time frame: 8 hours, 24 hours and 30 days post PCI
Population: FAS. N = number of participants with baseline and at least one post-baseline response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atorvastatin | Percentage of Participants With Elevated Creatine Kinase-MB (CK-MB) | 8 Hours Post-PCI | 11.3 percentage of participants |
| Atorvastatin | Percentage of Participants With Elevated Creatine Kinase-MB (CK-MB) | 24 Hours Post-PCI | 15.6 percentage of participants |
| Atorvastatin | Percentage of Participants With Elevated Creatine Kinase-MB (CK-MB) | 30 Days Post-PCI | 1.3 percentage of participants |
| Usual Care | Percentage of Participants With Elevated Creatine Kinase-MB (CK-MB) | 8 Hours Post-PCI | 13.6 percentage of participants |
| Usual Care | Percentage of Participants With Elevated Creatine Kinase-MB (CK-MB) | 24 Hours Post-PCI | 18.9 percentage of participants |
| Usual Care | Percentage of Participants With Elevated Creatine Kinase-MB (CK-MB) | 30 Days Post-PCI | 0.0 percentage of participants |
Comparison: 8 hours post-PCI: difference (%) in proportions. Null hypothesis = no difference in proportions of the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 0.63195% CI: [-10.1, 5.4]Chi-squared, Corrected
Comparison: 24 hours post-PCI: difference (%) in proportions. Null hypothesis = no difference in proportions of the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 0.51895% CI: [-12.1, 5.5]Chi-squared, Corrected
Comparison: 30 days post-PCI: difference (%) in proportions. Null hypothesis = no difference in proportions of the two groups. Fisher's exact test was applied because the expected frequency of biomarker elevation was less than 5.p-value: 0.23695% CI: [-9.6, 12]Fisher Exact
Secondary
Percentage of Participants With Elevated Myoglobin
Myoglobin above the upper limit of normal from baseline (biomarker of myocardial injury): normal range: 0-109 nanograms per milliliter (ng/mL).
Time frame: 8 hours, 24 hours and 30 days post PCI
Population: FAS. N = number of participants with baseline and at least one post-baseline response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atorvastatin | Percentage of Participants With Elevated Myoglobin | 30 days post-PCI | 1.3 percentage of participants |
| Atorvastatin | Percentage of Participants With Elevated Myoglobin | 8 hours post-PCI | 8.2 percentage of participants |
| Atorvastatin | Percentage of Participants With Elevated Myoglobin | 24 hours post-PCI | 3.1 percentage of participants |
| Usual Care | Percentage of Participants With Elevated Myoglobin | 8 hours post-PCI | 10.8 percentage of participants |
| Usual Care | Percentage of Participants With Elevated Myoglobin | 30 days post-PCI | 0.6 percentage of participants |
| Usual Care | Percentage of Participants With Elevated Myoglobin | 24 hours post-PCI | 4.2 percentage of participants |
Comparison: 8 hours post-PCI: difference (%) in proportions. Null hypothesis = no difference in proportions of the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 0.52995% CI: [-9.6, 4.3]Chi-squared, Corrected
Comparison: 24 hours post-PCI: difference (%) in proportions. Null hypothesis = no difference in proportions of the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 0.82795% CI: [-5.8, 3.6]Chi-squared, Corrected
Comparison: 30 days post-PCI: difference (%) in proportions. Null hypothesis = no difference in proportions of the two groups. Fisher's exact test was applied because the expected frequency of biomarker elevation was less than 5.p-value: 0.61695% CI: [-10.3, 11.5]Fisher Exact
Secondary
Percentage of Participants With Elevated Troponin I
Troponin I above the upper limit of normal range from baseline (biomarker of myocardial injury): normal range: 0-0.5 nanograms per milliliter (ng/mL).
Time frame: 8 hours, 24 hours and 30 days post PCI
Population: FAS. N = number of participants with baseline and at least one post-baseline response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atorvastatin | Percentage of Participants With Elevated Troponin I | 8 hours post-PCI | 40.4 percentage of participants |
| Atorvastatin | Percentage of Participants With Elevated Troponin I | 24 hours post-PCI | 49.7 percentage of participants |
| Atorvastatin | Percentage of Participants With Elevated Troponin I | 30 days post-PCI | 1.9 percentage of participants |
| Usual Care | Percentage of Participants With Elevated Troponin I | 8 hours post-PCI | 35.5 percentage of participants |
| Usual Care | Percentage of Participants With Elevated Troponin I | 24 hours post-PCI | 44.4 percentage of participants |
| Usual Care | Percentage of Participants With Elevated Troponin I | 30 days post-PCI | 1.8 percentage of participants |
Comparison: 8 hours post-PCI: difference (%) in proportions. Null hypothesis = no difference in proportions of the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 0.42595% CI: [-6.2, 15.9]Chi-squared, Corrected
Comparison: 24 hours post-PCI: difference (%) in proportions. Null hypothesis = no difference in proportions of the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 0.39295% CI: [-6.1, 16.7]Chi-squared, Corrected
Comparison: 30 days post-PCI: difference (%) in proportions. Null hypothesis = no difference in proportions of the two groups. Fisher's exact test was applied because the expected frequency of biomarker elevation was less than 5.p-value: 195% CI: [-10.7, 10.9]Fisher Exact
Secondary
Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 24 Hours Post-PCI
Percentage calculated as: (number of participants who experienced MACE within 24 hours post PCI) divided by (number of participants who experienced PCI) \* 100.
Time frame: 24 hours post PCI
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 24 Hours Post-PCI | 13.5 percentage of participants |
| Usual Care | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 24 Hours Post-PCI | 15.1 percentage of participants |
Comparison: Treatment difference (%). Null hypothesis = no difference between the incidence rates in the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 0.789695% CI: [-9.7, 6.5]Chi-squared, Corrected
Secondary
Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 8 Hours Post-PCI
Percentage calculated as: (number of participants who experienced MACE within 8 hours post-PCI) divided by (number of participants who experienced PCI) \* 100.
Time frame: 8 hours post PCI
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 8 Hours Post-PCI | 6.7 percentage of participants |
| Usual Care | Percentage of Participants With Major Adverse Cardiac Events (MACE) (Incidence of MACE) at 8 Hours Post-PCI | 6.4 percentage of participants |
Comparison: Treatment difference (%). Null hypothesis = no difference between the incidence rates in the two groups. A 5% two-sided continuity adjusted Chi-square test was applied.p-value: 195% CI: [-5.6, 6.3]Chi-squared, Corrected
Secondary
Percent Change From Baseline in C-Reactive Protein (CRP)
C-reactive protein percent change from baseline = (post baseline value minus baseline value) divided by baseline value\*100. Includes all CRP samples tested for the study, including samples unaffected and those samples affected by defective high-sensitivity (hs) CRP reagents.
Time frame: Baseline, 8 hours, 24 hours and 30 days
Population: FAS. N = number of subjects with non-missing values at baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin | Percent Change From Baseline in C-Reactive Protein (CRP) | 8 hours post-PCI | 205.25 percent change in CRP | Standard Error 67.799 |
| Atorvastatin | Percent Change From Baseline in C-Reactive Protein (CRP) | 24 hours post-PCI | 594.07 percent change in CRP | Standard Error 110.774 |
| Atorvastatin | Percent Change From Baseline in C-Reactive Protein (CRP) | 30 days post-PCI | 9.01 percent change in CRP | Standard Error 58.276 |
| Usual Care | Percent Change From Baseline in C-Reactive Protein (CRP) | 8 hours post-PCI | 234.77 percent change in CRP | Standard Error 66.135 |
| Usual Care | Percent Change From Baseline in C-Reactive Protein (CRP) | 24 hours post-PCI | 543.50 percent change in CRP | Standard Error 107.73 |
| Usual Care | Percent Change From Baseline in C-Reactive Protein (CRP) | 30 days post-PCI | 67.23 percent change in CRP | Standard Error 56.562 |
Comparison: 8 hours post-PCI: difference (% change).p-value: 0.755495% CI: [-215.87, 156.81]ANOVA
Comparison: 24 hours post-PCI: difference (% change).p-value: 0.743695% CI: [-253.42, 354.58]ANOVA
Comparison: 30 days post-PCI: difference (% change).p-value: 0.474195% CI: [-218.12, 101.68]ANOVA