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Achievement of Low-Density Lipoprotein Cholesterol Targets in CKD.

ABSTRACT: Introduction:We describe the characteristics of patients with moderate/advanced chronic kidney disease (CKD) according to receipt of lipid-lowering therapy (LLT), and whether they achieved low-density lipoprotein cholesterol (LDL-C) targets for high- and very high-risk patients. Methods:CKD-REIN (NCT03381950), a prospective cohort study conducted in 40 nephrology clinics in France, enrolled 3033 patients with moderate (stage G3) or advanced (stage G4/G5) CKD (2013-2016) who had not been on chronic dialysis or undergone kidney transplantation. Data were collected from patients' interviews and medical records. Patients were followed up at 1 year. Results:Among 2542 patients (mean [SD] age 67 [13] years, 34% women) with LDL-C measurements at baseline (mean [SD] LDL-C 2.7 [1.1] mmol/l; cholesterol 4.8 [1.3] mmol/l), 63% were on LLT; 24% were at high (CKD stage G3, no cardiovascular disease [CVD] or diabetes) and 74% at very high (CKD stage G3 with diabetes or CVD, or CKD stage G4/5) cardiovascular risk. Among high-risk patients, 45% of those on statin and/or ezetimibe achieved the LDL-C treatment target (<2.6 mmol/l). Among very high-risk patients, the percentage at goal (<1.8 mmol/l) was 38% for CKD stage G3 and 29% for stage G4/5. There was a trend toward higher achievement of LDL-C targets with increasing LLT intensity (adjusted odds ratios for moderate vs. low intensity 1.20; 95% confidence interval 0.92-1.56; high vs. low intensity 1.46; 1.02-2.09; P trend = 0.036). Conclusion:Many patients with CKD stage G3-G5 who are eligible for LLT are not treated, and those on LLT rarely achieve LDL-C targets.

SUBMITTER: Massy ZA

PROVIDER: S-EPMC6933478 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Achievement of Low-Density Lipoprotein Cholesterol Targets in CKD.

Massy Ziad A ZA Ferrières Jean J Bruckert Eric E Lange Céline C Liabeuf Sophie S Velkovski-Rouyer Maja M Stengel Bénédicte B

Kidney international reports 20190730 11

<h4>Introduction</h4>We describe the characteristics of patients with moderate/advanced chronic kidney disease (CKD) according to receipt of lipid-lowering therapy (LLT), and whether they achieved low-density lipoprotein cholesterol (LDL-C) targets for high- and very high-risk patients.<h4>Methods</h4>CKD-REIN (NCT03381950), a prospective cohort study conducted in 40 nephrology clinics in France, enrolled 3033 patients with moderate (stage G3) or advanced (stage G4/G5) CKD (2013-2016) who had no ...[more]

PMID: 31890996

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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: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: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.

Project description:Background Conventional "low-density lipoprotein cholesterol (LDL-C)" assays measure cholesterol content in both low-density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of "LDL-C" and corrected LDL-C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline-recommended LDL-C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from "LDL-C" to obtain corrected LDL-C values (LDL-Ccorr30). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual-patient-data meta-analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow-up). When comparing top versus bottom quartiles, the multivariable-adjusted hazard ratio for cardiovascular disease was significant for "LDL-C" (1.17; 95% CI, 1.05-1.31; P=0.005) but not for LDL-Ccorr30 (1.07; 95% CI, 0.93-1.22; P=0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline-recommended LDL-C categories when using LDL-Ccorr30 was assessed. In "LDL-C" categories of 70 to <100, 100 to <130, 130 to <190, and ?190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL-C categories when LDL-Ccorr30 was used: 30.2% (30.0%-30.4%), 35.1% (34.9%-35.4%), 32.9% (32.6%-33.1%), and 41.1% (40.0%-42.2%), respectively. Conclusions "LDL-C" was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL-C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.

Project description:Background MEDI6012 is recombinant human lecithin cholesterol acyltransferase, the rate-limiting enzyme in reverse cholesterol transport. Infusions of lecithin cholesterol acyltransferase have the potential to enhance reverse cholesterol transport and benefit patients with coronary heart disease. The purpose of this study was to test the safety, pharmacokinetic, and pharmacodynamic profile of MEDI6012. Methods and Results This phase 2a double-blind study randomized 48 subjects with stable coronary heart disease on a statin to a single dose of MEDI6012 or placebo (6:2) (NCT02601560) with ascending doses administered intravenously (24, 80, 240, and 800 mg) and subcutaneously (80 and 600 mg). MEDI6012 demonstrated rates of treatment-emergent adverse events that were similar to those of placebo. Dose-dependent increases in high-density lipoprotein cholesterol were observed with area under the concentration-time curves from 0 to 96 hours of 728, 1640, 3035, and 5318 should be: mg·h/mL in the intravenous dose groups and 422 and 2845 mg·h/mL in the subcutaneous dose groups. Peak mean high-density lipoprotein cholesterol percent change was 31.4%, 71.4%, 125%, and 177.8% in the intravenous dose groups and 18.3% and 111.2% in the subcutaneous dose groups, and was accompanied by increases in endogenous apoA1 (apolipoprotein A1) and non-ATP-binding cassette transporter A1 cholesterol efflux capacity. Decreases in apoB (apolipoprotein B) were observed across all dose levels and decreases in atherogenic small low-density lipoprotein particles by 41%, 88%, and 79% at the 80-, 240-, and 800-mg IV doses, respectively. Conclusions MEDI6012 demonstrated an acceptable safety profile and increased high-density lipoprotein cholesterol, endogenous apoA1, and non-ATP-binding cassette transporter A1 cholesterol efflux capacity while reducing the number of atherogenic low-density lipoprotein particles. These findings are supportive of enhanced reverse cholesterol transport and a functional high-density lipoprotein phenotype. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601560.

Dataset Information

Achievement of Low-Density Lipoprotein Cholesterol Targets in CKD.

Publications

Achievement of Low-Density Lipoprotein Cholesterol Targets in CKD.

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