Ischemic Stroke, Small Vessel Cerebrovascular Disease, Cholesterol, LDL, Secondary Prevention, Cardiovascular Diseases
Conditions
Keywords
Cerebral Small Vessel Diseases, Ischemic Stroke, Secondary Prevention, Cholesterol, LDL, Statins
Brief summary
Lipid-lowering therapy constitutes a cornerstone of secondary prevention in ischemic stroke; however, current stroke guidelines remain deficient in providing optimal target low-density lipoprotein (LDL)-cholesterol levels tailored to the stroke subtypes. Most clinical trials on LDL-cholesterol management have not differentiated between stroke subtypes or have primarily focused on large artery atherosclerosis (LAA) stroke, leaving a gap in evidence for managing LDL-cholesterol in other stroke subtypes, e.g., small vessel occlusion (SVO) stroke. While hypertension is the leading risk factor for SVO strokes, the link between elevated LDL-cholesterol and SVO stroke is also recognized. Establishing optimal LDL-cholesterol targets for SVO stroke would significantly enhance secondary prevention strategies and improve patient outcome. Thus, the investigators aim to compare intensive versus standard lipid-lowering in patients with SVO stroke. SVO70 is a multicenter, prospective, randomized, open, blinded-endpoint clinical trial. Adult participants with objectively confirmed SVO stroke within 180 days of randomization will be included. Exclusion criteria include those with predefined LDL-cholesterol targets for other conditions, statin contraindications, or women who are pregnant, breastfeeding, or planning pregnancy during the study period. Eligible participants will be randomized 1:1 to target LDL-cholesterol \<70 mg/dL (intensive group) or 90-110 mg/dL (standard group). The trial plans to enroll 4,016 participants, with the primary outcome being major adverse cardiovascular events-cardiovascular death, stroke, and acute coronary syndrome-during a follow-up period of at least 4 years. This study would provide valuable information for determining the optimal LDL-cholesterol target for patients with SVO stroke.
Interventions
Statin ± Ezetimibe to achieve target LDL-cholesterol level
DRUGPCSK9 inhibitor
The use of PCSK9 inhibitors is permitted to achieve target LDL-cholesterol levels in participants who did not reach the target with statins ± ezetimibe.
Sponsors
Hanmi Pharmaceutical co., ltd.
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) trial
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 19 years or older 2. Patients with objectively confirmed small vessel occlusive infarctions in the subcortical or brainstem regions, identified through neuroimaging (MRI or CT) 3. Patients with a history of symptomatic ischemic stroke caused by the lesion described in 2), occurring within 180 days prior to enrollment 4. Patients or guardians who agree to the study protocol and sign with informed consent
Exclusion criteria
1. Patients requiring intensive LDL cholesterol management (LDL-C \<70 mg/dL) due to another condition, with LDL cholesterol targets specified in the guidelines for that condition 2. Patients contraindicated for statin use (e.g., active liver disease, serum transaminase levels elevated more than three times the normal limit, muscle disorders, hypersensitivity to statins, or taking medications contraindicated for use with statins) 3. Women who are pregnant, breastfeeding, or intending to become pregnant during the study period 4. Deemed unsuitable for participation in the study for more than four years, as per the investigators' discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse cardiovascular event | 4 years | Major adverse cardiovascular event (MACE) includes cardiovascular death, stroke, and acute coronoary syndrome (i.e., ST-elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ischemic stroke or transient ischemic attack | 4 years | — |
| Cardiovascular death | 4 years | — |
| Any stroke | 4 years | Ischemic stroke, transient ischemic attack, or hemorrhagic stroke |
| Any death | 4 years | — |
| Acute coronary syndrome | 4 years | ST-elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina |
| Myocardial infarction | 4 years | — |
Countries
South Korea
Contacts
Primary ContactWookjin Yang, MD, PhD
Backup ContactSeung-Hoon Lee, MD, PhD
Outcome results
None listed