Early Initiation of Tafolecimab for Patients With Acute Coronary Syndromeundergoing Percutaneous Coronary Intervention in Chinese Population

Not Applicable

Not yet recruiting

• Conditions: Acute Coronary Syndrome; Non ST Segment Elevation Acute Coronary Syndrome
• Interventions: Drug: Cholesterol Absorption Inhibitor; Drug: Tafolecimab; Drug: Statin

• Registration Number: NCT06096909
• Lead Sponsor: China National Center for Cardiovascular Diseases

Brief Summary

For patients with ACS undergoing PCI, intensive lipid-lowering including PCSK9 monoclonal antibody should be started as soon as possible, that is, lower LDL-C level should be achieved as soon as possible. Compared with conventional lipid-lowering regimen, it is expected that the occurrence of major adverse cardiovascular events can still be reduced after drug discontinuation. Therefore, the optimization strategy of "for patients with ACS undergoing PCI, intensive lipid-lowering with PCSK9 monoclonal antibody can be started as soon as possible" is proposed.

Detailed Description

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide, and its incidence is increasing yearly in China, which has not yet reached the inflection point. Acute coronary syndrome (ACS) is a severe form of ASCVD, and lipid-lowering and antithrombotic therapy are the two core therapies. In the latest ESC/EAS guidelines for lipid management, for ACS patients, the target LDL-C is \<1.4 mmol/L and ≥50% reduction from baseline, and specific initiatives to achieve this target are proposed, emphasizing the timing of clinical application and status of the novel lipid-lowering agent-proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9) (hereafter referred to as PCSK9 antibody). In recent years, large-scale randomized controlled trials and outcomes of PCSK9 antibodies have demonstrated that PCSK9 antibodies further reduce adverse cardiovascular events by significantly lowering LDL-C levels under the background statin (±cholesterol absorption inhibitor ) therapy. The introduction of PCSK9 antibodies allowed for the reduction of LDL-C to unprecedented levels. From the "cholesterol principle" perspective, it is theoretically reasonable to add a PCSK9 inhibitor to statins as soon as possible during hospitalization for ACS patients. Still, there is no clear evidence from large RCTs. Current evidence supports that for ACS patients, PCSK9 antibodies could be used only when LDL-C is still not up to standard based on treatment with the maximum tolerable dose of statins during the first 2-3 months. However, the immediate initiation of PCSK9 antibodies during the acute phase of ACS (before hospital discharge) has yet to be studied.

Study Timeline

• Study First Submitted: 2023-09-28
• Status Verified: 2023-10
• Study First Submitted QC: 2023-10-20
• Last Update Submitted: 2023-10-20
• Study First Posted: 2023-10-24
• Last Update Posted: 2023-10-24
• Study Start: 2023-11-01
• Primary Completion: 2025-11-01
• Study Completion: 2027-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 3684

Inclusion Criteria

• Patients aged 18 to 75 years;
• clinical diagnosis with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) ;
• undergoing PCI
• baseline LDL-C 1.8 mmol/L 3.4 mmol/L note: NSTE-ACS includes non-ST-elevation myocardial infarction and unstable angina.

Exclusion Criteria

• Severe heart failure (Killip III or IV) or cardiogenic shock;
• Previous hemorrhagic cerebrovascular disease history;
• Uncontrolled or recurrent arrhythmic events;
• poorly controlled hypertension;
• Severe hepatic and renal insufficiency (ALT/AST> 3 times upper limit of normal, eGFR<30 ml/kg/1.73m2, or ongoing dialysis) or creatine kinase elevation>5 times upper limit of normal
• malignant tumor;
• Intolerance to statins or cholesterol absorption inhibitors;
• Intolerance to injections;
• Life expectancy <1 year;
• poor compliance.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
control group	Cholesterol Absorption Inhibitor	conventional lipid lowering therapy
experimental group	Statin	intensive lipid lowering therapy
control group	Statin	conventional lipid lowering therapy
experimental group	Tafolecimab	intensive lipid lowering therapy

Primary Outcome Measures

Name	Time	Method
Major adverse cardiovascular and cerebrovascular events (MACCE)	at the end of 2 years	Including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, and coronary revascularization). The coronary revascularization includes coronary intervention (PCI), coronary artery bypass grafting (CABG).

Secondary Outcome Measures

Name	Time	Method
major adverse cardiovascular events (MACEs)	at the end of 6 months	Cardiovascular death, nonfatal myocardial infarction, hospitalization for unstable angina, and coronary revascularization.
Major adverse cardiovascular and cerebrovascular events (MACCE)	at the end of 1 years	Including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, and coronary revascularization). The coronary revascularization includes coronary intervention (PCI), coronary artery bypass grafting (CABG).