ETACS: PCSK 9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients With ACS After PCI
Study Details
Study Description
Brief Summary
The primary objective was to evaluate the effect of PCSK 9 Inhibitor (initiated within 4 h from PCI for the culprit lesion) with high-intensity statin treatment, compared to placebo with high-intensity statin treatment, on cardiovascular events (including cardiovascular death, myocardial infarction, stroke or transit ischemic attack, re-hospitalization due to unstable angina or heart failure, or any ischemia-driven coronary revascularization) in patients with acute coronary syndrome and multiple lesions.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Patients with acute coronary syndrome (ACS) are at high-risk. ACS patients are commonly associated with multiple lesions or multivessel disease. Percutaneous coronary intervention (PCI) is an effective treatment for culprit lesions in ACS. Statin at high-intensity is recommended by current guidelines in order to prevent/slow the progression of non-culprit disease or restenosis. PCSK9 inhibitor serves as the most powerful medication in lowering LDL via promoting the expression of LDL receptors in the liver. However, if the combination of PCSK9 inhibitor with high-intensity statin treatment could significantly reduce the cardiovascular events in patients with ACS who underwent PCI remains unknown.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo plus high-intensity statin Participants received placebo subcutaneous injections once every 2 weeks (Q2W) plus high-intensity statin treatment (Rosuvastatin, 20 mg, once daily) |
Drug: Placebo plus high-intensity statin
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen, Q2W, and oral administration of rosuvastatin (20 mg, once daily).
|
| Active Comparator: PCSK 9 Inhibitor plus high-intensity statin Participants received PCSK 9 Inhibitor Q2W subcutaneous injections |
Drug: PCSK 9 Inhibitor plus high-intensity statin
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen, Q2W, and oral administration of rosuvastatin (20 mg, once daily).
|
Outcome Measures
Primary Outcome Measures
- Cardiovascular events [12 months after randomization]
Cardiovascular events defined as the composite of cardiovascular death, myocardial infarction, stroke or transit ischemic attack, re-hospitalization due to unstable angina or heart failure, or any ischemia-driven coronary revascularization.
Secondary Outcome Measures
- Cardiovascular death [12 months after randomization]
It will be adjudicated by an independent external CEC according to protocol defined definition.
- All cause death [12 months after randomization]
It is defined as any death from randomization to the last visit.
- Myocardial infarction [12 months after randomization]
It will be adjudicated by an independent external CEC.
- Stroke or transient ischemic attack (TIA) [12 months after randomization]
stroke or TIA will be adjudicated by an independent external CEC.
- Ischemia-driven coronary revascularization [12 months after randomization]
It will be adjudicated by an independent external CEC.
- Re-hospitalization due to unstable angina or heart failure [12 months after randomization]
It will be adjudicated by an independent external CEC.
- Diagnostic malignant tumor [12 months after randomization]
It will be adjudicated by an independent external CEC.
- Clinical relevant bleeding [12 months after randomization]
It will be adjudicated by an independent external CEC. The BARC defined clinical relevant bleeding includes BARC 2-5
- PCSK9 inhibitors or statin intolerance [12 months after randomization]
It will be adjudicated by an independent external CEC.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female, age ≥18 y at screening
-
Patients with ACS who underwent PCI for culprit lesions. ACS defined as:
- Unstable angina, defined as rest pain lasting for 5-30 minutes or deteriorative exertional angina with either a) transient ST segment depression or elevation, or
- angiography showing a visually estimated diameter stenosis ≥90% or a ruptured plaque or thrombotic lesion
-
Non-ST elevation myocardial infarction (NSTEMI), defined as positive troponin consistent with clinical syndrome and non-ST-segment elevation
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ST elevation MI (STEMI), defined as positive troponin consistent with clinical syndrome and ST-segment elevation
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LDL-C ≥70 mg/dL (≥1.8 mmol/L) assessed prior to, or during PCI in patients who have been receiving any stable statin regimen ≥4 wk prior to enrolment; or LDL-C ≥90 mg/dL (≥2.3 mmol/L) in patients who have been on moderate or low intensity statin regimen prior to enrollment; or LDL-C ≥125 mg/dL (≥3.2 mmol/L) in patients who are statin-naïve or have not been on stable statin regimen for ≥4 wk prior to enrollment
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At least one major native coronary artery ("diseased vessels") or lesion meeting the following criteria following the qualifying PCI procedure:
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Angiographic evidence of <50% diameter stenosis
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Diseased vessel must not be a bypass (saphenous vein or arterial) graft or a bypassed native vessel
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Diseased vessel must not have undergone previous PCI prior-to enrollment
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Hemodynamic stability allowing the repetitive administration of nitroglycerine if necessary
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Ability to understand the requirements of the study and to provide informed consent
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Willingness of patient to undergo follow-up procedures and visits
Exclusion Criteria:
-
Patients in whom the qualifying index ACS event occurred > 30 days prior to randomization
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Fasting low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL (< 1.8 mmol/L) if on stable statin treatment for minimal 4 weeks; OR LDL-C <90 mg/dL (<2.3 mmol/L) in patients who have been on moderate or low intensity statin regimen prior to enrollment; OR LDL-C <125 mg/dL (< 3.2 mmol/L) in patients who are statin-naïve or have not been on stable statin regimen for ≥4 wk prior to enrollment
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Fasting serum triglycerides (TG) >400 mg/dL (>4.52 mmol/L) prior to randomization
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History of coronary artery bypass surgery
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Residual diameter stenosis >50% by visual examination after PCI of the culprit lesion
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TIMI flow <2 after culprit vessel PCI
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Unstable clinical status (hemodynamic or electrical instability)
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Uncontrolled hypertension (multiple readings with SBP > 180 mmHg or DBP > 110 mmHg)
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New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction < 30%
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Known history of hemorrhagic stroke less than 180 days prior to randomization
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Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response not controlled by medications in the past 3 mo prior to screening
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Severe renal dysfunction, defined by estimated glomerular filtration rate <30 ml/min/1.73m^2
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Active liver disease or hepatic dysfunction
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Known intolerance to rosuvastatin OR known statin intolerance
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Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel or clopidogrel
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Patients who previously received PCSK9 inhibitor
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Patient who received cholesterol ester transfer protein inhibitors in the past 12 mo prior to screening
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Treatment with systemic steroids or systemic cyclosporine in the past 3 mo
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Known active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator
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Planned Non-cardiac surgery within 12 mo
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Patients who will not be available for study-required visits in the judgment of the Investigator
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Current enrolment in another investigational device or drug study
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History of cancer within the past 5 y, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
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Estimated life expectancy less than 12 mo
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Female of childbearing potential (age <50 y and last menstruation within the last 12 mo), who did not undergo tubal ligation, ovariectomy or hysterectomy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nanjing First Hospital | Nanjing | Jiangsu | China | 210006 |
Sponsors and Collaborators
- Nanjing First Hospital, Nanjing Medical University
- National Natural Science Foundation of China
- Nanjing Medical University
Investigators
- Study Chair: Shao-Liang Chen, MD, PhD, Nanjing First Hospital, Nanjing Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NMU20220701