Lipoprotein cholesterol (LDL-C) reduction in patients with ischemic stroke is greater when treated with moderate-intensity rosuvastatin plus ezetimibe as opposed to high-intensity rosuvastatin alone, according to study findings published in the Journal of Stroke.
In the event of an ischemic stroke or transient ischemic attack in those with accompanying atherosclerotic disease, LDL-C lowering agents are recommended to reduce subsequent vascular events. First line strategies consist of high dosage statins, in spite of undesired side effects (myopathy, hepatic dysfunction, diabetes). Recent studies have shown LDL-C reduction to be greater when moderate intensity statins were coupled with nonstatin lipid-lowering therapies, such as ezetimibe compared with standalone high intensity statins. As no randomized trials exist that compare their efficacy postischemic stroke, researchers aimed to compare the utility of statins plus ezetimibe vs high intensity statins in regards to LDL-C goal achievement in patients with recent ischemic stroke of atherosclerotic origin.
The researchers conducted a randomized, multi center group trial, ROSETTA-Stroke (ClinicalTrials.gov Identifier: NCT03993236), across 13 sites in South Korea. Groups comprised rosuvastatin 10 mg plus ezetimibe 10 mg once daily (ROS10/EZT10) and rosuvastatin 20 mg alone once daily (ROS20), where patients were randomly assigned in a 1:1 ratio. Eligible patients were aged ≥19 years and had a confirmed ischemic stroke within 90 days, confirmed by diffusion-weighted imaging. Individuals also had baseline LDL-C measured after onset of stroke, and had subsequent lipid profiles collected at follow-up visits.
Primary endpoint was attaining target LDL-C goal, defined as LDL-C reduction of ≥50% from baseline. The key secondary endpoints included LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events.
A total of 530 patients were included in the final comparison study, with 273 in the ROS10/EZT10 group and 257 in the ROS20 group.
Baseline LDL-C level was 130.2 mg/dL in the ROS10/EZT10 group and 131.0 mg/dL in the ROS20 group. LDL-C reduction of ≥50% from baseline was found in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [OR], 1.944; 95% CI, 1.352–2.795; P =.0003).
A higher proportion of patients achieving LDL-C level <70 mg/dL were found in the ROS10/EZT10 group when compared with the ROS20 group (80.2% vs. 65.4%; OR, 2.148; 95% CI, 1.450–3.184; P =.0001). Additionally, absolute LDL-C reduction was greater in the ROS10/EZT10 group when compared with the ROS20 group (72.7 mg/dL vs. 64.7 mg/dL; P =.0111).
Baseline high density lipoprotein cholesterol and triglyceride levels were comparable at baseline between the 2 groups; and at 90 day follow up, baseline levels did not differ between the groups.
Rates of adverse events were similar between both groups (36.9% vs. 36.9%; P =.9969); myalgia occurred in 2.3% of patients in the ROS10/EZT10 group, compared with 1.4% in the ROS20 group (P =.5000).
Limitations of the study included its open-label design, which may have led to reporting bias of clinical events. Generalizability may also be limited, as enrolled patients were exclusively Korean.
“[T]he combination of moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg was superior to high-intensity rosuvastatin 20 mg alone for LDL-C reduction in patients with recent ischemic stroke who initiated lipid-lowering therapy,” the researchers concluded.
Disclosures: Several study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.
Hong KS, Bang OY, Park JH, et al. Moderate-intensity rosuvastatin plus ezetimibe vs high-intensity rosuvastatin for target low-density lipoprotein cholesterol goal achievement in patients with recent ischemic stroke: a randomized controlled trial. Stroke. Published online April 11, 2023. doi:10.5853/jos.2022.02957