Acute Coronary Syndrome, Non ST Segment Elevation Acute Coronary Syndrome, Lipid Lowering, Vascular Inflammation
Conditions
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.
Interventions
DRUGTafolecimab
The PCSK9 mAb in this study is defined as Tafolecimab 150mg q2w subcutaneously. For the two groups of lipid-lowering regimens, the lipid-lowering drug regimens other than PCSK9 mAb were maintained throughout the study as much as possible in accordance with the guidelines related to blood lipids, provided that no serious safety problems occurred.
DRUGCholesterol Absorption Inhibitor
Cholesterol absorption inhibitors (like Ezetimibe and Hybutimibe) are based on physician decisions, but need to be routinely dosed. Examples of Medications that Meet Study Requirements: Ezetimibe 10mg Po qd.
DRUGStatin
Statin are based on physician decisions, but need to be routinely dosed. Examples of Medications that Meet Study Requirements: Atorvastatin 20mg Po qn, Rosuvastatin 10mg Po qn or Pitavastatin 4mg Po qn.
Sponsors
China National Center for Cardiovascular Diseases
Innovent Biologics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
The study is open-label because participants and doctors cannot be blinded due to the nature of intervention and the ethical restrictions (blank injections are not allowed). However, the data collectors, statisticians and independent events adjudication committee will be blinded to intervention allocation. In addition, the results of study will be measured objectively without considering the influence induced by unblinded intervention.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse cardiovascular and cerebrovascular events (MACCE) | week 104 | The primary endpoint of this trial is major adverse cardiovascular and cerebrovascular events at visit 4 (week 104), defined as the composite endpoints of cardiovascular death, nonfatal MI, nonfatal stroke, hospitalization for unstable angina and coronary revascularization. Coronary revascularization included PCI or coronary artery bypass grafting (CABG). The coronary revascularization will be conducted based on the presence of ischemia. To evaluate the ischemic need for coronary revascularization, specific assessments will be utilized. Laboratory examinations will include blood tests to check for markers of myocardial injury, such as troponins. Electrocardiograms will be assessed. Unstable angina is defined as typical angina symptoms that have worsened in the past month, with a single episode lasting more than half a minute and that do not resolve spontaneously. The definition of MI is referenced from the fourth Universal Definition of Myocardial Infarction (UDMI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| major adverse cardiovascular and cerebrovascular events | week 26 | The key secondary endpoint is the incidence of MACCE at week 26 (Visit 2), defined as a composite of cardiovascular death, nonfatal MI, nonfatal stroke, hospitalization for unstable angina, and coronary revascularization. |
| A composite of primary outcome or all-cause death | Week 104 | Including all-cause death, 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). |
| Lipid control outcome | week 104 | Lipid control outcome is the proportion of patients achieving an LDL-C reduction of ≥50% from baseline and attaining an LDL-C level of \<1.4 mmol/L. |
Countries
China
Contacts
CONTACTNa-Qiong Wu, Doctor
CONTACTZheng Yin, Doctor
PRINCIPAL_INVESTIGATORNa-Qiong Wu, Doctor
Chinese Academy of Medical Sciences, Fuwai Hospital
PRINCIPAL_INVESTIGATORYong-Jian Wu, Doctor
Chinese Academy of Medical Sciences, Fuwai Hospital
Outcome results
None listed