Study on the Composite Endpoint Event of PCSK9 Inhibitor in Patients With Very High Risk of ASCVD and Cancer

Study Overview
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Brief Summary
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This study is a prospective, randomized, open-label, and single center trial. To evaluate the effect of treatment with PCSK9 inhibitor on the risk for cardiovascular death, recurrent unstable angina, myocardial infarction, stroke, or coronary revascularization in patients with very high risk of atherosclerotic cardiovascular disease (ASCVD) and cancer.

Detailed Description
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Subjects will be randomly assigned in a 1:1 ratio to receive subcutaneous injections of PCSK9 inhibitor (evolocumab:420 mg every 4 weeks) plus moderate intensity statin therapy or the statin alone therapy. After randomization, patients will come to the hospital every 4 weeks to collect relevant laboratory results and clinical outcomes, and be detected by echocardiography and carotid ultrasound every 12 weeks until the end of follow-up at week 48 or the occurrence of an endpoint event. The entire study is expected to be conducted for 3 years, with a recruitment period of 2 years.

Official Title
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Study on the Composite Endpoint Event of PCSK9 Inhibitor in Patients With Very High Risk of ASCVD and Cancer

Conditions
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ASCVD, Atherosclerotic Cardiovascular Disease, Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor, Cancer

Intervention / Treatment
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* Drug: Evolocumab
* Drug: Statin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 to ≤ 80 years of age Patients with very high risk of ASCVD (with any of the following): Documented ASCVD, either clinical or unequivocal on imaging. Documented ASCVD includes previous acute coronary syndrome (ACS), stable angina, coronary revascularization (percutaneous coronary intervention, coronary artery bypass graft, and other arterial revascularization procedures), stroke and transient ischemic attack (TIA), and peripheral arterial disease. Unequivocally documented ASCVD on imaging includes those findings that are known to be predictive of clinical events, such as significant plaque on coronary angiography or computed tomography (CT) scan (multivessel coronary disease with two major epicardial arteries having >50% stenosis), or on carotid ultrasound. Diabetes mellitus (DM) with target organ damage, or at least three major risk factors, or early onset of type 1 diabetes mellitus (T1DM) of long duration (>20 years). Patients have been diagnosed with cancer through histopathology and have a life expectancy of more than 1 year Fasting low-density lipoprotein cholesterol (LDL-C) ≥ 1.8 mmol/L or non-high-density lipoprotein cholesterol (non HDL-C) > 2.6 mmol/L Participate voluntarily and sign an informed consent Negative serum Pregnancy test (in women with fertility potential) Exclusion Criteria: Pregnant and lactating women During the study period and within 3 months of receiving the last dose of the study drug, women with fertility intentions and men unwilling to use effective contraceptive methods New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction < 30% Uncontrolled hypertension, defined as systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg Plan for coronary revascularization or other cardiac surgery in recent (within 3 months after randomization) Severe renal insufficiency, defined as estimated glomerular filtration rate (eGRF) < 30ml/min/1.73m2 or Serum creatinine (Scr) > 221 umol/L Severe liver dysfunction, defined as an increase in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3 times above the upper limit of normal Have used PCSK9 inhibitors within 3 months before enrollment, or have a history of severe allergic reactions to PCSK9 inhibitors Severe infections requiring intravenous antibiotics HIV-positive or history of acquired immunodeficiency syndrome (AIDS) With cognitive impairment or psychiatric illnesses Participating in other trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: patients with very high risk of ASCVD and cancer
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: the PCSK9 inhibitor plus statin therapy<br>Patients with very high risk of ASCVD and cancer are treated with moderate intensity statin daily and evolocumab (420 mg) every 4 weeks throughout the study period. | Drug: Evolocumab<br>* Evolocuma:420 mg every 4 weeks<br>* Other names: Repatha;Drug: Statin<br>* The moderate intensity statins used during the study are one of atorvastatin 10-20mg qd, resuvastatin 5-10mg qd, and xuezhikang 0.6g bid (statin intolerance).<br>|
| Other: the statin alone therapy<br>Patients with very high risk of ASCVD and cancer are treated with moderate intensity statin daily throughout the study period. | Drug: Statin<br>* The moderate intensity statins used during the study are one of atorvastatin 10-20mg qd, resuvastatin 5-10mg qd, and xuezhikang 0.6g bid (statin intolerance).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major cardiovascular adverse events | Major cardiovascular adverse events include cardiovascular death, recurrent unstable angina, myocardial infarction, stroke, and coronary revascularization | From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause death | All cause death | From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks | 
| Composite end points | Composite end points include cardiogenic shock, cardiac arrest, malignant arrhythmia, heart failure, Non-coronary revascularization | From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks | 
| The compliance rate of lipid control | Main indicator: LDL-C decreased to below 1.4 mmol/L and decreased by more than 50% from baseline; secondary indicator: non HDL-C<2.2 mmol/L; | From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks | 
| The changes of carotid plaque | By carotid ultrasound | From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASCVD, cancer, PCSK9