Acute Coronary Syndromes, Chronic Coronary Syndrome, High Risk Patient, Percutaneous Coronary Intervention
Conditions
Keywords
Acute coronary syndrome, Chronic coronary syndrome, Percutaneous coronary intervention, LDL-C, lipid
Brief summary
Extensive evidence from epidemiological, genetic, and randomized controlled trials (RCTs) of lipid-lowering therapies has firmly established a causal relationship between low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD), establishing LDL-C as both a pathogenic risk factor and a critical therapeutic target. Lipid-lowering therapies targeting LDL-C have significantly decreased the overall risk in ASCVD patients. Consequently, current guidelines recommend, based on risk stratification, lowering LDL-C levels in high-risk ASCVD patients to \<1.4 mmol/L with a ≥50% reduction from baseline. Findings from PROVE IT-TIMI 22, IMPROVE-IT, ODYSSEY OUTCOMES, and FOURIER-OLE trials suggest that achieving extremely low LDL-C levels may further reduce the risk of cardiovascular events in ASCVD patients without substantially increasing clinically relevant adverse events; however, randomized data was still scarce in supporting this notion. Against these backgrounds, we have designed this trial to investigate whether targeting LDL-C levels \<0.8 mmol/L in high-risk ASCVD patients results in a significant reduction in adverse events compared to targeting LDL-C levels of 0.8-1.4 mmol/L.
Interventions
OTHERIntensive LDL-C control
By Statin, Ezetimibe, or PCSK9i, prescribed according to LDL-C level at baseline and follow-up; For patients with baseline LDL-C level \< 3.0 mmol/L, it is recommended to start lipid control by statin + PCSK9i; for LDL-C level ≥ 3.0 mmol/L, statin + ezetimibe + PCSK9i
OTHERConventional LDL-C control
By Statin, Ezetimibe, or PCSK9i, prescribed according to LDL-C level at baseline and follow-up; For patients with baseline LDL-C level \< 3.0 mmol/L, it is recommended to start lipid control by statin alone or statin + ezetimibe; for LDL-C level ≥ 3.0 mmol/L, statin + PCSK9i
Sponsors
Xijing Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients underwent percutaneous coronary intervention due to acute or chronic coronary syndrome 2. Patients with ASCVD at extremely high risk 3. Patients who are able to complete the follow-up and compliant with the allocated treatment * ASCVD at extremely high risk is defined as fulfilling at least TWO of the following criteria: 1. PCI for acute myocardial infarction (AMI, including STEMI or NSTEMI) 2. Previous AMI, previous stroke, or previous intervention or surgery for peripheral vascular disease 3. Experienced cardiovascular event(s) with LDL-C≤1.8mmol/L 4. LDL-C≥4.9mmol/L 5. Diabetes 6. CKD (eGFR \< 60 ml/min/1.73m2) 7. Current smoking 8. Recurrent cardio/cerebrovascular events 9. History of premature ASCVD (\< 55 male, \< 65 female) 10. Complex PCI (fulfilling at least one of the following criteria: multivessel disease; in-stent restenosis; ≥ 3 stents implanted; total stent length ≥ 60 mm; bifurcation; left main disease; target lesions allocated in bypass graft; chronic total occlusion (≥ 3 months of occlusion))
Exclusion criteria
1. Age less than 18 years; 2. Unable to give informed consent or currently participating in other trials; 3. Patient who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to randomization in women of child-bearing potential according to local practice), or plans to become pregnant during treatment; 4. Concurrent medical condition with a life expectancy of less than 3 years; 5. Hemodynamic unstable; 6. Active liver disease or hepatic dysfunction (persistent unexplained ALT/AST elevations (≥ 3 × ULN)), patients with a transient increase ALT/AST due to the acute MI may be enrolled; 7. Unable to reach the LDL-C target by known intolerance or contradiction of lipid control medications; 8. LDL-C ≤ 1.4 mmol/L at baseline without any lipid control medication lowering LDL-C; 9. Known active infection or critical hematologic/endocrine dysfunction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Adverse Cardiovascular and Cerebrovascular Events | 24 months | MACCE, a composite of cardiovascular death, stroke, myocardial infarction, and any revascularization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular death | 24 months | Cardiovascular death is considered as other secondary endpoint |
| Ischemic stroke | 24 months | Ischemic stroke is considered as other secondary endpoint |
| Hemorrhagic stroke | 24 months | Hemorrhagic stroke is considered as other secondary endpoint |
| Revascularization | 24 months | Revascularization is considered as other secondary endpoint |
| Target lesion revascularization | 24 months | Target lesion revascularization is considered as other secondary endpoint |
| Clinically and physiologically-indicated target lesion revascularization | 24 months | Clinically and physiologically-indicated target lesion revascularization is considered as other secondary endpoint |
| Cardiovascular hospitalization | 24 months | Cardiovascular hospitalization is considered as other secondary endpoint |
| Patient-oriented composite endpoint | 24 months | PoCE, a composite of all-cause death, stroke, myocardial infarction, revascularization, is the first major secondary outcome. |
| Device-oriented Composite Endpoint | 24 months | DoCE, a composite of cardiovascular death, target vessel myocardial infarction, clinically and physiologically-indicated target lesion revascularization, is the second major secondary outcome. |
| Composite of all-cause death, stroke, and myocardial infarction | 24 months | The composite of all-cause death, stroke, and myocardial infarction is the third major secondary outcome. |
| All-cause death | 24 months | All-cause death is considered as other secondary endpoint |
| Myocardial infarction | 24 months | Myocardial infarction is considered as other secondary endpoint |
| Stroke | 24 months | Stroke is considered as other secondary endpoint |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacological costs | 24 months | Pharmacological costs is considered as exploratory endpoint |
| All adverse events | 24 months | All adverse events is defined by CTCAE V5.0, considered as safety endpoint |
| All serious adverse events | 24 months | All serious adverse events is defined by CTCAE V5.0, considered as safety endpoint |
| Adverse events of interest | 24 months | Adverse events of interest, including minor bleeding, major bleeding, injection site reactions, allergic reactions, muscle-related adverse events, rhabdomyolysis, cataracts, adjudicated case of new-onset diabetes, neurocognitive disorders, AST/ALT elevation \>3 times the upper limit of normal, creatine kinase elevation \>5 times the upper limit of normal, which is considered as safety endpoint Adverse events of interest is the safety endpoint. |
| EuroQol-5D-5L | 24 months | EuroQol-5D-5L is considered as exploratory endpoint |
| Everyday Cognition Questionnaire | 24 months | Everyday Cognition Questionnaire is considered as exploratory endpoint |
Countries
China
Contacts
Primary ContactChao Gao, M.D., Ph.D.
Outcome results
None listed