Dataset Information

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial.

ABSTRACT:

Background and purpose

Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke.

Methods

This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events.

Results

Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352-2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups.

Conclusion

Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.

SUBMITTER: Hong KS

PROVIDER: S-EPMC10250871 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial.

Hong Keun-Sik KS Bang Oh Young OY Park Jong-Ho JH Jung Jin-Man JM Lee Sang-Hun SH Song Tae-Jin TJ Nam Hyo Suk HS Park Hee-Kwon HK Jung Keun-Hwa KH Heo Sung Hyuk SH Koo Jaseong J Yu Kyung-Ho KH Park Kwang-Yeol KY Kim Chi Kyung CK Park Hong-Kyun HK Lee Jiyoon J Lee Juneyoung J Seo Woo-Keun WK

Journal of stroke 20230411 2

<h4>Background and purpose</h4>Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke.<h4>Methods</h4>This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from base ...[more]

PMID: 37032475

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Project description:BACKGROUND:It is important to achieve the low-density lipoprotein cholesterol (LDL-C) goal recommended by clinical guidelines in managing the risk of cardiovascular (CV) events, however, the current management of LDL-C in actual clinical settings is suboptimal. We examined the LDL-C level among patients with dyslipidemia against the 2015 Korean guidelines, the crude rates of CV events based on LDL-C goal achievement, and the factors associated with LDL-C goal achievement. METHODS:This was a retrospective cohort study using the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from 2006 to 2013. Patients who had a health examination with LDL-C measurement between January 1, 2007, and December 31, 2011 were identified. Patients were required to have at least one diagnosis of dyslipidemia during the 1 year before the index date, defined as the first date of LDL-C measurement. The 2015 Korean guidelines were used to measure LDL-C goal achievement based on the CV risk level. Crude CV event rates were calculated for total and individual CV events as the number of events divided by person-years (PYs) during the follow-up period. CV events included acute coronary syndrome, ischemic stroke, peripheral artery disease, CV death, and all-cause death. Factors associated with LDL-C goal achievement were assessed using logistic regression. RESULTS:In the NHIS-HEALS database, 69,942 patients met the eligibility criteria: 36.7%, 22.5%, 20.1%, and 20.6% were among the very high-, high-, moderate-, and low-risk groups for the CV events, respectively, as defined by the 2015 Korean guidelines. Approximately half of the patients with dyslipidemia (47.6%) achieved their recommended LDL-C goal, but the achievement rates were substantially different across CV risk levels (17.6%, 47.2%, 66.9%, and 82.4% for very high-, high-, moderate-, and low-risk groups, respectively; P<0.0001). The crude event rate of total CV events during the follow-up period in the LDL-C goal non-achievers was higher than that in the LDL-C goal achievers (24.35/100 PYs vs. 11.93/100 PYs; P<0.0001). LDL-C goal achievement was significantly associated with patient characteristics, including age, sex, body mass index, lipid-modifying therapy, and CV risk level. CONCLUSIONS:In South Korea, LDL-C goal achievement among patients with very high or high CV risk was suboptimal. Patients who did not achieve the goal showed a higher rate of CV events during the follow-up period than patients who achieved the goal. LDL-C management strategies should be highlighted in dyslipidemia patients who are less likely to achieve the goal, such as female, overweight or obese patients, patients not adherent to statin, or patients with very high or high CV risk.

Project description:BackgroundThe importance of low-density lipoprotein cholesterol (LDL-C) lowering to reduce atherosclerotic cardiovascular disease (ASCVD) risk is strongly emphasized. If the LDL-C goals are not achieved with statin therapy, combination with ezetimibe is recommended. Studies revealed a substantial gap between obtained LDL-C levels and LDL-C target in ASCVD patients. However, little is known about the achievement of LDL-lowering treatment targets in ASCVD patients receiving ezetimibe in addition to statins.Materials and methodsThis was a retrospective cohort study based on EHR data from the regional health information system of Yinzhou, an eastern coastal area of China. ASCVD Patients stratified as very high risk, taking both statin and ezetimibe for lipid control, and had at least one lipid test after ezetimibe initiation were included between January 2013 and July 2020. Descriptive statistics were used to summarize the LDL-C values and target value (1.8 mmol/L according to the Chinese guideline, 1.4 mmol/L according to the European guideline) achievements. Multivariable logistic regression was used to explore the influencing factors of target achievement rate.ResultsA total of 1,727 patients were included. The median follow-up time was 15.0 months. Taking 1.8 mmol/L as the target value, the achievement rates of LDL-C over the first 3 follow up years were 50.6, 31.3, and 30.3%, respectively. Taking 1.4 mmol/L as the target value, the achievement rates were 25.6, 15.5, and 16.5%, respectively. Multivariable analysis suggested that male patients (OR = 1.78, 95%CI: 1.27-2.49), combined use of atorvastatin or rosuvastatin with ezetimibe (vs other statins, OR = 4.64, 95% CI: 1.83-11.76), better medication adherence (OR = 1.03, 95% CI: 1.01-1.04) and smoking cessation (vs smoking, OR = 2.26, 95% CI: 1.27-4.02) were associated with a higher achievement rate, while baseline LDL-C level (OR = 0.48, 95% CI: 0.41-0.56) and treatment course of statin before ezetimibe (OR = 0.93, 95% CI: 0.89-0.98) were negatively associated with achievement rate.ConclusionLong-term follow-up data based on a Chinese regional database shows that in very high-risk ASCVD patients taking ezetimibe in addition to statins, achievement rate of LDL-lowering treatment targets is still low and far from satisfactory in real-world setting. More efforts are needed to achieve optimal LDL-C levels.

Project description:Dyslipidemia, atherosclerosis, and cardiovascular events can be prevented, or treated, using statins, alone or in combination with ezetimibe. The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe and their combinations on endothelial cells damaged by oxidized cholesterol. HUVEC cultures were stimulated for 20 hours with atorvastatin (5 μM; 2793 ng/mL), rosuvastatin (10 μM; 4815 ng/mL), ezetimibe (1.22 μM; 500 ng/mL), atorvastatin plus ezetimibe (5 μM + 1.22 μM; 2793 ng/mL + 500 ng/mL) and rosuvastatin plus ezetimibe (10 μM + 1.22 μM; 4815 ng/mL + 500ng/mL) in separate groups, with or without 25-hydroxycholesterol pre-incubation (24.83 μM; 10 μg/mL; four hours then washout). HUVEC integrity was measured in the RTCA-DP xCELLigence system. The mRNA expression and protein levels of ZO-1, OCLN, ICAM-1 were analyzed by real-time PCR and ELISA. Pre-incubation with 25-OHC resulted in decreased endothelial cell integrity (p<0.001), decreased expression of ZO-1 mRNA (p<0.05) and protein levels (p<0.05), OCLN mRNA (p<0.05) and protein levels (p<0.05) and increased ICAM-1 mRNA (p<0.001) and protein levels (p<0.001) compared to the control group. Incubation with rosuvastatin (12h p<0.01; 24h p<0.001) and atorvastatin (only 12h p<0.05) restored HUVEC integrity. Subsequent incubation with rosuvastatin increased ZO-1 mRNA (p<0.001) and protein (p<0.001) levels. Subsequent addition of ezetimibe increased ZO-1 mRNA level (p<0.001) but not protein level. Furthermore, only incubation with rosuvastatin increased OCLN mRNA (p<0.05) and protein (p<0.05) levels. In each drug-stimulated group, both ICAM-1 mRNA and protein levels were reduced after initial incubation with oxysterol (p<0.05). 25-hydroxycholesterol disrupts endothelial integrity, decreases the mRNA and protein levels of tight junction, and increases those of intercellular adhesion molecules. Both rosuvastatin and atorvastatin can improve endothelial integrity, but only rosuvastatin can completely abolish the effect of oxysterol. The combination of statins with ezetimibe has less direct effect on the endothelial barrier than the statins alone.

Project description:Background Exercise is associated with a reduced risk of cardiovascular disease. Increased high-density lipoprotein cholesterol (HDL-C) levels are thought to contribute to these benefits, but much of the research in this area has been limited by lack of well-controlled subject selection and exercise interventions. We sought to study the effect of moderate and high-intensity exercise on HDL function, lipid/lipoprotein profile, and other cardiometabolic parameters in a homogeneous population where exercise, daily routine, sleep patterns, and living conditions were carefully controlled. Methods and Results Male Army recruits (n=115, age 22±0.3 years) completed a 12-week moderate-intensity exercise program. A subset of 51 subsequently completed a 15-week high-intensity exercise program. Fitness increased and body fat decreased after moderate- and high-intensity exercise (P<0.001). Moderate-intensity exercise increased HDL-C and apolipoprotein A-I levels (6.6%, 11.6% respectively), and decreased low-density lipoprotein cholesterol and apolipoprotein B levels (7.2%, 4.9% respectively) (all P<0.01). HDL-C and apolipoprotein A-I levels further increased by 8.2% (P<0.001) and 6.3% (P<0.05) after high-intensity exercise. Moderate-intensity exercise increased ABCA-1 (ATP-binding cassette transporter A1) mediated cholesterol efflux by 13.5% (P<0.001), which was sustained after high-intensity exercise. In a selected subset the ability of HDLs to inhibit ICAM-1 (intercellular adhesion molecule-1) expression decreased after the high (P<0.001) but not the moderate-intensity exercise program. Conclusions When controlling for exercise patterns, diet, and sleep, moderate-intensity exercise improved HDL function, lipid/lipoprotein profile, fitness, and body composition. A sequential moderate followed by high-intensity exercise program showed sustained or incremental benefits in these parameters. Improved HDL function may be part of the mechanism by which exercise reduces cardiovascular disease risk.

Project description:Low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor for atherosclerotic cardiovascular disease. It is unclear whether the percentage LDL-C lowering with pharmacotherapies differs on the basis of baseline LDL-C levels. To evaluate the association between baseline LDL-C levels and the percentage LDL-C reduction with a statin, ezetimibe, and a PCSK9 inhibitor. This secondary exploratory study analyzed data from 3 randomized placebo-controlled clinical trials (Aggrastat to Zocor-Thrombolysis in Myocardial Infarction 21 [A to Z-TIMI 21], Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT], and Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]) of lipid-lowering therapies (statin, ezetimibe, and a PCSK9 inhibitor) and included participants with atherosclerotic cardiovascular disease. Analyses took place form April to October 2020. In A to Z-TIMI 21, 1:1 randomization to simvastatin, 40 mg, daily for 30 days followed by 80 mg daily thereafter vs placebo for 4 months followed by simvastatin, 20 mg, daily thereafter. In IMPROVE-IT, 1:1 randomization to ezetimibe, 10 mg, daily plus simvastatin, 40 mg, daily vs placebo plus simvastatin, 40 mg, daily. In FOURIER, 1:1 randomization to evolocumab, 140 mg, every 2 weeks or 420 mg monthly vs matching placebo. The percentage LDL-C reduction at either 1 month (A to Z-TIMI 21, IMPROVE-IT) or 3 months (FOURIER) as a function of baseline LDL-C level. Data were modeled using a generalized linear regression model. A total of 3187 patients from A to Z-TIMI 21, 10 680 patients from IMPROVE-IT, and 25 847 patients from FOURIER were analyzed. There was a higher percentage reduction in LDL-C levels with evolocumab in patients with lower baseline LDL-C levels, ranging from 59.4% (95% CI, 59.1%-59.8%) in patients with a baseline LDL-C level of 130 mg/dL to 66.1% (95% CI, 65.6%-66.6%) in patients with a baseline LDL-C level of 70 mg/dL (P < .001). In contrast, across the same range of baseline LDL-C level, there was a more modest difference for simvastatin (44.6% [95% CI, 43.9%-45.2%] vs 47.8% [95% CI, 46.4%-49.2%]; P < .001) and minimal difference with ezetimibe (25.0% [95% CI, 23.3%-26.6%] vs 26.2% [95% CI, 24.2%-28.1%]; P = .007). The percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels and is 6.6% greater for PCSK9 inhibition. These data are encouraging for the use of intensive LDL-C-lowering therapy even for patients with lower LDL-C levels.

Dataset Information

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial.

Background and purpose

Methods

Results

Conclusion

Publications

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial.

Similar Datasets

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