Evolocumab Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients With ACS After PCI

• Status: Not yet recruiting
• Trial end date: 2029-01-30
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective was to evaluate the effect of evolocumab (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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nanjing First Hospital, Nanjing Medical University
• Collaborators: Nanjing Medical University; National Natural Science Foundation of China
• Treatments: Evolocumab; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Criteria

Inclusion Criteria:

• Male or female, age ≥18 y at screening

• Patients with ACS who underwent PCI for culprit lesions. ACS defined as:

1. 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 b) angiography showing a visually estimated diameter stenosis ≥90% or a ruptured plaque or thrombotic lesion

2. Non-ST elevation myocardial infarction (NSTEMI), defined as positive troponin consistent with clinical syndrome and non-ST-segment elevation

3. ST elevation MI (STEMI), defined as positive troponin consistent with clinical syndrome and ST-segment elevation

• 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

• At least one major native coronary artery ("diseased vessels") or lesion meeting the following criteria following the qualifying PCI procedure:

1. Angiographic evidence of <50% diameter stenosis

2. Diseased vessel must not be a bypass (saphenous vein or arterial) graft or a bypassed native vessel

3. Diseased vessel must not have undergone previous PCI prior-to enrollment

• Hemodynamic stability allowing the repetitive administration of nitroglycerine if necessary

• Ability to understand the requirements of the study and to provide informed consent

• 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

• 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

• Fasting serum triglycerides (TG) >400 mg/dL (>4.52 mmol/L) prior to randomization

• History of coronary artery bypass surgery

• Residual diameter stenosis >50% by visual examination after PCI of the culprit lesion

• TIMI flow <2 after culprit vessel PCI

• Unstable clinical status (hemodynamic or electrical instability)

• Uncontrolled hypertension (multiple readings with SBP > 180 mmHg or DBP > 110 mmHg)

• New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction < 30%

• Known history of hemorrhagic stroke less than 180 days prior to randomization

• 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

• Severe renal dysfunction, defined by estimated glomerular filtration rate <30 ml/min/1.73m^2

• Active liver disease or hepatic dysfunction

• Known intolerance to rosuvastatin OR known statin intolerance

• Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel or clopidogrel

• Patients who previously received alirocumab or other PCSK9 inhibitor

• Patient who received cholesterol ester transfer protein inhibitors in the past 12 mo prior to screening

• Treatment with systemic steroids or systemic cyclosporine in the past 3 mo

• Known active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator

• Planned Non-cardiac surgery within 12 mo

• Patients who will not be available for study-required visits in the judgment of the Investigator

• Current enrolment in another investigational device or drug study

• 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

• Estimated life expectancy less than 12 mo

• Female of childbearing potential (age <50 y and last menstruation within the last 12 mo), who did not undergo tubal ligation, ovariectomy or hysterectomy.