Optimal LDL-C Target in High-risk Patients After PCI

Official title

Targeting LDL-C to Less Than 0.8 mmol/L in Patients After PCI With High Risk of Cardiovascular Disease: an Open-label, Assessor-blinded, Randomized Trial (REC-SAFETARGET Trial)

Overview

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

• Other Intensive 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
• Other Conventional 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

Primary outcome measures

• Major Adverse Cardiovascular and Cerebrovascular Events [Time frame: 24 months]

Secondary outcome measures (12)

• Patient-oriented composite endpoint [Time frame: 24 months]
• Device-oriented Composite Endpoint [Time frame: 24 months]
• Composite of all-cause death, stroke, and myocardial infarction [Time frame: 24 months]
• All-cause death [Time frame: 24 months]
• Cardiovascular death [Time frame: 24 months]
• Myocardial infarction [Time frame: 24 months]
• Stroke [Time frame: 24 months]
• Ischemic stroke [Time frame: 24 months]
• Hemorrhagic stroke [Time frame: 24 months]
• Revascularization [Time frame: 24 months]
• Target lesion revascularization [Time frame: 24 months]
• Clinically and physiologically-indicated target lesion revascularization [Time frame: 24 months]

Eligibility criteria

Inclusion criteria

• Patients underwent percutaneous coronary intervention due to acute or chronic coronary syndrome
• Patients with ASCVD at extremely high risk
• 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:

• PCI for acute myocardial infarction (AMI, including STEMI or NSTEMI)
• Previous AMI, previous stroke, or previous intervention or surgery for peripheral vascular disease
• Experienced cardiovascular event(s) with LDL-C≤1.8mmol/L
• LDL-C≥4.9mmol/L
• Diabetes
• CKD (eGFR < 60 ml/min/1.73m2)
• Current smoking
• Recurrent cardio/cerebrovascular events
• History of premature ASCVD (< 55 male, < 65 female)
• 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

• Age less than 18 years;
• Unable to give informed consent or currently participating in other trials;
• 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;
• Concurrent medical condition with a life expectancy of less than 3 years;
• Hemodynamic unstable;
• 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;
• Unable to reach the LDL-C target by known intolerance or contradiction of lipid control medications;
• LDL-C ≤ 1.4 mmol/L at baseline without any lipid control medication lowering LDL-C;
• Known active infection or critical hematologic/endocrine dysfunction.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Xijing Hospital — Xi'an

Identifiers

NCT: NCT06821711 · KY20242295-F-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗