Switching to rosuvastatin plus ezetimibe in statin-treated stroke patients with low-density lipoprotein cholesterol levels above 70 mg/dL (SWITCH): a prospective observational study

Yang et al. Lipids in Health and Disease (2025) 24:359 https://doi.org/10.1186/s12944-025-02781-6 Lipids in Health and Disease Open Access RESEARCH Switching to rosuvastatin plus ezetimibe in statin-treated stroke patients with lowdensity lipoprotein cholesterol levels above 70 mg/dL (SWITCH): a prospective observational study Wookjin Yang1, Yeong-Bae Lee2, Eung-Gyu Kim3, Han-Jin Cho4, Sungwook Yu5, Joon-Tae Kim6, Jong Wook Shin7, Soo Joo Lee8, Beom Joon Kim9, Ji Man Hong10, Seong-Ho Koh11, Sang Joon An12, A-Hyun Cho13, Jin-Man Jung14, Hyun-Ji Cho15, Chulho Kim16, Eung-Joon Lee17, Jeong-Min Kim17 and Seung-Hoon Lee17* Abstract Background Effective lipid management is critical for secondary stroke prevention, however, many patients fail to achieve target low-density lipoprotein cholesterol (LDL-C) levels with statin monotherapy. This study evaluated the real-world effectiveness and safety of switching from statin monotherapy to rosuvastatin plus ezetimibe combination therapy (REZ) in patients with stroke. Methods This multicenter, prospective, observational study enrolled patients with stroke and baseline LDL-C ≥ 70 mg/dL despite statin monotherapy from 16 Korean stroke centers. Participants were switched to REZ at doses of 5/10 mg, 10/10 mg, or 20/10 mg at the investigators’ discretion. Lipid profiles were assessed at three and six months. The primary outcome was achieving LDL-C < 70 mg/dL at six months. Results In total, 1,431 participants enrolled between May 2021 and March 2023 were eligible (mean age 65.3 ± 10.6 years; 66.8% male). Among 994 participants completing follow-up, the mean baseline LDL-C was 98.9 ± 22.4 mg/dL. At six months, 708 (71.2%) achieved LDL-C < 70 mg/dL. Mean LDL-C decreased to 62.7 ± 22.1 mg/dL at three months and to 62.0 ± 22.0 mg/dL at six months. The effectiveness of REZ remained consistent across different REZ dosages and regardless of changes in statin intensity during the switch. REZ was particularly effective in patients with diabetes (odds ratio [95% confidence interval], 1.85 [1.32–2.59]; P < 0.001) and baseline LDL-C 70–99 mg/dL (2.71 [2.04–3.59]; P < 0.001). Fewer participants achieved stricter targets (LDL-C < 55 mg/dL or LDL-C < 70 mg/dL plus 50% reduction). Conclusions Switching to REZ effectively reduced LDL-C in patients with stroke receiving statin monotherapy with LDL-C ≥ 70 mg/dL, offering potential benefits for secondary cardiovascular prevention in real-world practice. Keywords Ezetimibe, Hydroxymethylglutaryl-CoA reductase inhibitors, Low-density lipoprotein cholesterol, Stroke *Correspondence: Seung-Hoon Lee Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Yang et al. Lipids in Health and Disease (2025) 24:359 Introduction Patients with stroke are at high risk of recurrent stroke and other cardiovascular diseases (CVDs), necessitating effective secondary prevention strategies. Lipid-lowering therapy is a cornerstone of mitigating recurrent CVD risk, with accumulating evidence supporting progressively lower low-density lipoprotein cholesterol (LDLC) targets [1–7], summarized by the widely recognized notion that “the lower, the better”. Current stroke guidelines also recommend high-intensity statin for non-cardioembolic stroke and advocate achieving LDL-C levels below 70 mg/dL in patients with atherosclerotic disease, based on the SPARCL and TST trials [8–10]. Given the high prevalence of coexisting atherosclerotic disease among patients with stroke [11, 12], achieving stringent LDL-C targets below 70 mg/dL is essential for effective secondary prevention. Statins are the first-line agents for lipid-lowering therapy and are widely prescribed. However, many patients, particularly those with ischemic stroke, face challenges managing cholesterol with statin monotherapy due to higher cholesterol levels and significant atherosclerotic burden, necessitating additional lipid-lowering agents [13, 14]. In such cases, the combination of statin and ezetimibe, demonstrated by the IMPROVE-IT study to significantly enhance LDL-C reduction and cardiovascular outcomes [3], has become a widely used strategy in clinical practice. Nevertheless, real-world data on the effectiveness and safety of this combination, especially among patients with stroke in Korea, remains limited. Thus, this study aimed to evaluate the effectiveness and safety of switching to a rosuvastatin plus ezetimibe combination therapy (REZ) in Korean patients with stroke who were already on statins but did not achieve an LDL-C level of < 70 mg/dL in routine clinical practice. It was hypothesized that switching to REZ would lead to meaningful LDL-C reduction without compromising safety. Methods Study design and population This prospective, observational, non-interventional, single-group study was conducted at 16 Korean stroke centers, with patient enrollment between May 2021 and March 2023. Adult participants aged ≥ 19 years with a history of stroke and an LDL-C level ≥ 70 mg/dL despite statin monotherapy were eligible. Exclusion criteria were: (1) hypersensitivity to rosuvastatin or ezetimibe; (2) active liver disease; (3) muscular disorders; (4) concomitant cyclosporin use; (5) severe renal disease whose creatinine clearance < 30 mL/min; (6) pregnancy or breastfeeding; and (7) other conditions deemed unsuitable by investigators. Following the baseline lipid profile assessment, eligible participants were switched from Page 2 of 9 statin monotherapy to REZ. The dose of REZ was determined at the physicians’ discretion, and lipid profiles were monitored three and six months after the switch. This study was approved by the institutional review board (IRB) of Seoul National University Hospital (IRB No. H-2103-061−1204) and the IRBs of all participating sites. Written informed consent was obtained from all participants or their caregivers/guardians. Clinical information For all participants, data on age, sex, height, weight, comorbidities (hypertension, diabetes, dyslipidemia, atrial fibrillation, and coronary artery disease), smoking status, time since stroke diagnosis, stroke subtype, (...truncated)