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Achievement of specified lipid and high-sensitivity C-reactive protein levels with two statins in Chinese patients with hypercholesterolaemia.

ABSTRACT: Statins reduce plasma low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) levels. Rosuvastatin 10 mg daily appears to be more potent in reducing LDL-C than simvastatin 40 mg, but the relative effect of these two statin doses on hsCRP is unknown.Chinese hyperlipidaemic patients with high cardiovascular risk or familial hypercholesterolaemia (FH) were treated with rosuvastatin 10 mg and simvastatin 40 mg daily in an open-label crossover study. Lipid profiles were measured off treatment and after at least 4 weeks treatment with each of the two statins and hsCRP levels were measured on treatment with both statins.Both treatments were well tolerated in 247 patients (age 55.7 ± 11.1 years; 100 male; 140 with FH) with good treatment compliance. There were statistically significant differences (P < 0.001) for rosuvastatin versus simvastatin for LDL-C reduction (-52.4 ± 11.9 % vs. -47.7 ± 10.8 %) and on-treatment LDL-C (2.62 ± 0.99 mmol/L vs. 2.86 ± 0.97 mmol/L), respectively, but the on-treatment hsCRP levels (1.33 ± 1.37 mg/L vs. 1.41 ± 1.57 mg/L, P > 0.05) were not significantly different. The lipid target (LDL-C <2.6 mmol/L) was achieved by 52.9 % with rosuvastatin compared with 42.6 % with simvastatin (P < 0.05). The proportions of patients attaining hsCRP targets of < 2 and < 1 mg/L were similar with the two statins (57.1 % and 74.6 % for rosuvastatin vs. 57.1 % and 80.1 % for simvastatin, P > 0.05).A significantly greater proportion of patients achieved LDL-C targets with rosuvastatin 10 mg compared to simvastatin 40 mg in Chinese patients with hypercholesterolaemia, but there was no significant difference in achieving hsCRP target levels with the two statins.

SUBMITTER: Ding C

PROVIDER: S-EPMC4568069 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Achievement of specified lipid and high-sensitivity C-reactive protein levels with two statins in Chinese patients with hypercholesterolaemia.

Ding Cheng C Hu Miao M Wu Yong-Jian YJ Tomlinson Brian B

Lipids in health and disease 20150913

<h4>Background</h4>Statins reduce plasma low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) levels. Rosuvastatin 10 mg daily appears to be more potent in reducing LDL-C than simvastatin 40 mg, but the relative effect of these two statin doses on hsCRP is unknown.<h4>Methods</h4>Chinese hyperlipidaemic patients with high cardiovascular risk or familial hypercholesterolaemia (FH) were treated with rosuvastatin 10 mg and simvastatin 40 mg daily in an open-la ...[more]

PMID: 26365713

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Project description:BackgroundHomozygous familial hypercholesterolaemia (HoFH) is characterized by a markedly increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide reduces low-density lipoprotein cholesterol (LDL-C) levels; however, the probable impact on LDL-C goals and CV events is unknown.MethodsWe used data collected in the first 26 weeks of the lomitapide pivotal phase 3 study (NCT00730236) to evaluate achievement of European Atherosclerosis Society (EAS) LDL-C targets. We used publicly available data reporting major adverse CV events (MACE) rates from other cohorts of HoFH patients to compare event rates for an equivalent number of patient years of exposure (98) in the lomitapide extension trial (NCT00943306).ResultsTwenty-nine patients were included in the phase 3 study. During the first 26 weeks, 15 (51%) and eight (28%) reached LDL-C targets of 100 mg/dL and 70 mg/dL, respectively, at least once. Fourteen (74%) and 11 (58%) of the 19 patients who remained in the extension study after week 126 reached LDL-C targets of 100 mg/dL and 70 mg/dL at least once during the entire study period. Only two MACE were reported in the lomitapide trials (one cardiac death and one coronary artery bypass graft (CABG)) - equivalent to 1.7 events per 1000 patient months of treatment. MACE rates were 21.7, 9.5 and 1.8 per 1000 patient-months respectively in cohorts of HoFH patients pre- and post-mipomersen, and receiving evolocumab. On treatment LDL-C levels were 166, 331 and 286 mg/dL for lomitapide, mipomersen and evolocumab, respectively.ConclusionsApproximately three quarters and half of patients who took lomitapide for at least 2 years reached LDL-C goals of 100 mg/dL and 70 mg/dL, respectively. There were fewer major CV events per 1000 patient months of treatment in patients taking lomitapide, mipomersen or evolocumab than reported in the mipomersen cohort prior to starting mipomersen. These results support the hypothesis that novel lipid-lowering therapies may reduce CV events in HoFH patients by lowering LDL-C further.Trial registrationNCT00730236 (registered 8 Aug 2008) and NCT00943306 (registered 22 July 2009).

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:Oxysterols (OHC) are biologically active cholesterol metabolites circulating in plasma that may be formed enzymatically (e.g. 24S-OHC, 25-OHC and 27-OHC) or by autoxidative mechanisms (e.g. 7-ketocholesterol, 7β-OHC and 25-OHC). Oxysterols are more soluble than cholesterol and are reported to exert inflammatory, cytoprotective and apoptotic effects according to concentration and species. Esterified oxysterols have been analysed in people with dementia and cardiovascular diseases although there is no consistent relationship between oxysterol esters and disease. However, oxysterol esters are held in lipoprotein core and may not relate to the concentration and activity of plasma free oxysterols. Methodological limitations have challenged the analysis of free oxysterols to date. We have developed a fast, sensitive and specific quantitative LC-MS/MS, multiple reaction monitoring (MRM) method to target five oxysterols in human plasma with analyte recoveries between 72% and 82% and sensitivities between 5 and 135 pg/ml. A novel method was used to investigate the hypothesis that simvastatin may reduce the concentrations of specific plasma free oxysterols in hypercholesterolaemia. Twenty healthy male volunteers were recruited (aged 41-63 years); ten were asymptomatic with high plasma cholesterol > 6.5 mM and ten were healthy with normal plasma cholesterol (< 6.5 mM). Simvastatin (40 mg/day) was prescribed to those with hypercholesterolaemia. Plasma samples were taken from both groups at baseline and after three months. Simvastatin reduced plasma cholesterol by ~35% (p < 0.05) at the end of three months. Oxysterols generated by autoxidation (but not enzymatically) were elevated up to 45 fold in hypercholesterolaemic midlife men. Plasma oxysterols were restored to those of healthy controls after simvastatin intervention suggesting that autoxidation is either prevented by simvastatin directly or that autoxidation is less prevalent when plasma cholesterol concentrations are within the normal range.

Dataset Information

Achievement of specified lipid and high-sensitivity C-reactive protein levels with two statins in Chinese patients with hypercholesterolaemia.

Publications

Achievement of specified lipid and high-sensitivity C-reactive protein levels with two statins in Chinese patients with hypercholesterolaemia.

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