Significant Reductions In LDL-C Research Articles

The current LDL-C target <1.4mmol/l of the ESC is achieved in less than 16% of patients with Coronary Heart Disease despite effective lipid-lowering therapy: data from the LLT-R registry

Abstract Background In the current guideline of the ESC, in patients with very high cardiovascular risk such as coronary heart disease (CHD) a treatment target for LDL-C <1.4mmol/l and/or a halving of the initial value are defined. It is unclear whether these treatment targets are achievable with standard therapy including statins and/or ezetemibe. Methods The primary objective of this prospective, multi-centre register study was the question of the guidance-based adaptation and adherence to lipid-lowering therapy during and after a cardiac rehabilitation in 1,100 patients with CHD up to 12 months after discharge from the six rehabilitation clinics involved. Patients were included from 2016 to 2018. Results The median age of the 1,100 patients was 63.4±10.4 years, the mean BMI was 28.5±4.7kg/m2, and 24.1% of patients were female. 12.2% were active smokers, 91.6% reported dyslipoproteinemia, 33.9% suffered from diabetes mellitus and 86.5% from hypertension. The majority of patients were included with the main indications NSTEMI (31.6%), STEMI (29.6%) and after CABG surgery (26.4%). The proportion of patients treated with statins was more than 94% when admitted and discharged from the rehabilitation clinic, as well as in 3- and 12-months follow-ups. Approximately 9% of patients were treated with ezetemibe at baseline. On discharge from the rehabilitation clinic 23% of patients were treated with ezetemibe, which remains stable at 3 and 12 months. PCSK9 inhibitors were used in 0.1–0.3% of patients at all times. The adjustment of LLT during three week cardiac rehabilitation resulted in median LDL-C values of 2.27mmol/l (1.80/2.84) at baseline, 1.97mmol/l (1.57/2.47) on discharge (p<0.001 compared to baseline), 1.94mmol/l (1.57/2.49) after three months and 1.94mmol/l (1.53/2.40) after 12 months. The proportion of patients with LDL-C <1.4mmol/l was 9% at baseline, 15.7% on discharge (p<0.001 compared to baseline), 15.6% at three-month follow-up and 15.1% at 12-month follow-up (Figure 1). Discussion In the context of cardiac rehabilitation, an effective adjustment of LLT is carried out, which resulted in a significant reduction of LDL-C. However, despite a high percentage of patients on statins and ezetemibe, the proportion of patients in the new target range <1.4mmol/l was only achievable in a small percentage and the question arises whether these treatment targets can be achieved without additional administration of PCSK9 inhibitors in majority of patients with CHD. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was supported by an unrestricted grant from Sanofi-Aventis Germany.

Grape seed extract supplementation along with a restricted-calorie diet improves cardiovascular risk factors in obese or overweight adult individuals: A randomized, placebo-controlled trial.

Grape seed extract (GSE) is a flavonoid-rich supplement, recently discussed as a potential moderator of inflammation and obesity. In this study, we aimed to investigate the effects of GSE supplementation along with a restricted-calorie diet (RCD), on changes in blood lipid profile, visceral adiposity index (VAI), and atherogenic index of plasma (AIP). We designed a randomized, double-blinded, placebo-controlled clinical trial. Forty obese or overweight individuals (25 ≤ body mass index < 40 kg/m2 ) were randomly assigned to receive GSE (300 mg/day) or placebo, plus RCD, for 12 weeks. We studied the anthropometric measures, biochemical biomarkers and dietary intake within the study timelines. Levels of high-density lipoprotein cholesterol (HDL-C) and HDL-C/low-density lipoprotein cholesterol (LDL-C) significantly increased in the GSE group as compared with the placebo group at week 12 (p = .03 and .008, respectively, adjusted for age, sex, energy and saturated fatty acid intake). We also observed a significant reduction in LDL-C following GSE supplementation in comparison to placebo (adjusted for age, sex and energy intake, p = .04). VAI, AIP, total cholesterol and triglyceride significantly decreased in the GSE group compared with the baseline (p = .04, .02, .01, and .02, respectively). GSE supplementation may have a modulatory role in improving blood lipid profile in obese or overweight individuals, when accompanied by RCD.

Clinical profile of patients treated with evolocumab in lipid/internal medicine units of Spain. Observational study (RETOSS-IMU)

ObjectiveTo describe the clinical characteristics, the reasons for initiating therapy, and the effects of treatment in the initial phase of evolocumab availability in Lipid/ Internal Medicine Units in Spain. MethodsRetrospective, observational study, based on the medical records of consecutive patients initiating treatment with evolocumab (from February 2016 to July 2017), in 20 Internal Medicine Units in Spain. A review was made of the demographic and clinical characteristics of the patients, the lipid lowering treatment, and the evolution of the lipid profiles between 12 weeks pre-initiation and 12 ± 4 weeks post-initiation of evolocumab. ResultsA total of 136 patients were analysed, of whom 64.0% were men, and the mean age (standard deviation, SD) was 56.6 (11.5) years. The large majority (75%) had familial hypercholesterolaemia (FH) (4 homozygous), and 51.0% of them had suffered at least one cardiovascular event. Atherosclerotic cardiovascular disease (ASCVD) was present in 61% of all patients. At initiation of evolocumab, 61.0% of the patients were taking high-intensity statins, and 60.3% were receiving ezetimibe. The mean (and SD) of LDL-c levels at initiation of evolocumab was 169.1 (56.6) mg/dL. The LDL-c was greater than 160 mg/dL in 46.4% of patients, and ≥190 mg/dL in 26.5%. During the observation period, evolocumab produced significant reductions in LDL-c of 55.7% (p < .0001), achieving mean values of 74.3 mg/dL. At week 12, more than half (53.8%) of patients achieved LDL-c levels <70 mg/dL, and 26.9% <50 mg/dL. ConclusionsIn the Lipid/Internal Medicine Units, evolocumab was mainly prescribed in patients with FH, with or without ASCVD. The initial use of evolocumab was in accordance with the guidelines of the Spanish Society of Arteriosclerosis (SEA) of 2016, with LDL-c levels being well above the recommended thresholds for treatment initiation. Evolocumab treatment in clinical practice reduced LDL-C levels by about 55%, a similar reduction to that reported in clinical trials. Most patients achieved LDL-c goals.

Perfil clínico de los pacientes tratados con evolocumab en unidades de lípidos/medicina interna en España. Estudio observacional (RETOSS-IMU)

ObjectiveTo describe the clinical characteristics, the reasons for initiating therapy, and the effects of treatment in the initial phase of evolocumab availability in lipid/internal medicine units in Spain. MethodsRetrospective, observational study, based on the medical records of consecutive patients initiating treatment with evolocumab (from February 2016 to July 2017) in 20 internal medicine units in Spain. A review was made of the demographic and clinical characteristics of the patients, the lipid lowering treatment, and the evolution of the lipid profiles between 12weeks pre-initiation and 12±4weeks post-initiation of evolocumab. ResultsA total of 136 patients were analysed, of whom 64.0% were men, and the mean age (standard deviation, SD) was 56.6 (11.5) years. The large majority (75%) had familial hypercholesterolaemia (4 homozygous), and 51.0% of them had suffered at least one cardiovascular event. Atherosclerotic cardiovascular disease (ASCVD) was present in 61% of all patients. At initiation of evolocumab, 61.0% of the patients were taking high-intensity statins, and 60.3% were receiving ezetimibe. The mean (and SD) of LDL-C levels at initiation of evolocumab was 169.1 (56.6) mg/dL. The LDL-C was greater than 160mg/dL in 46.4% of patients, and ≥190mg/dL in 26.5%. During the observation period, evolocumab produced significant reductions in LDL-C of 55.7% (P<.0001), achieving mean values of 74.3mg/dL. At week12, more than half (53.8%) of patients achieved LDL-C levels <70mg/dL, and 26.9% <50mg/dL. ConclusionsIn the lipid/internal medicine units, evolocumab was mainly prescribed in patients with familial hypercholesterolaemia, with or without ASCVD. The initial use of evolocumab was in accordance with the guidelines of the Spanish Society of Arteriosclerosis (SEA) of 2016, with LDL-C levels being well above the recommended thresholds for treatment initiation. Evolocumab treatment in clinical practice reduced LDL-C levels by about 55%, a similar reduction to that reported in clinical trials. Most patients achieved LDL-C goals.

The SYDNEY Device Study: A Multicenter, Randomized, Open-label Usability Study of a 2-mL Alirocumab Autoinjector Device

PurposeThe proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has produced significant reductions in LDL-C at a dose of 300 mg q4w administered as 2 separate 150-mg injections via a 1-mL autoinjector (AI). A recently developed 2-mL device (SYDNEY) permits the administration of a single 300mg dose of alirocumab. MethodsWe assessed the usability and product technical complaints (PTCs) reported by patients using the 2-mL SYDNEY device in unsupervised settings, adverse events, and effects on LDL-C, in a multicenter, randomized, open-label, 16-week study conducted in the United States. For their first dose, 69 patients with hypercholesterolemia despite receiving statin with or without other lipid-lowering therapy randomly received supervised, self-administered alirocumab 300 mg via 1 × 300 mg injection with the SYDNEY device (n = 35) or 2 × 150-mg injections with the currently approved AI (n = 34). All continuing patients subsequently received unsupervised, self-administered alirocumab 300 mg q4w using the SYDNEY device at weeks 4, 8, and 12. The primary end point was the proportion of SYDNEY device–associated PTCs related to the use of the unsupervised injections. FindingsBaseline characteristics between the study arms varied only in a higher percentage of males being randomized to the study arm using the SYDNEY device (74.3%) compared with the AI arm (44.1%). A single PTC was reported during the unsupervised injections (0.5%; 1 of 196 injections; 95% CI, 0.0%–3.2%). This event was classified as patient related as opposed to device related. No PTCs occurred during supervised injections. Mean LDL-C reductions from baseline at week 4 were 66.2% with SYDNEY and 51.2% with the AI; after adjustment for sex differences between groups, mean LDL-C reductions were 63.5% and 53.9%, respectively. LDL-C reductions persisted for 16 weeks. The most common adverse event was upper respiratory tract infection (3 with SYDNEY and 0 with the AI during weeks 0–4). ImplicationsThe SYDNEY device allowed for a single 2-mL injection of alirocumab 300 mg, providing substantial LDL-C reductions with no new product technical issues or no new safety concerns compared with the currently marketed 1-mL AI device. In conclusion, the 2-mL SYDNEY device provides patients with the possibility of injecting the 300-mg alirocumab dose as a single injection. ClinicalTrials.gov identifier: NCT03415178.

P6194Therapeutic effect of nanoliposomal anti-PCSK9 vaccine on hypercholesterolemia and atherosclerosis in C57BL/6 mice

Abstract Background Proprotein convertase subtilisin/kexin 9 (PCSK9) promotes hypercholesterolemia through reducing protein level of liver low-density lipoprotein (LDL) receptor (LDLR). Currently, PCSK9 inhibition is known as an efficient lipid-lowering approach. Purpose Here, we constructed a liposomal anti-PCSK9 vaccine, and evaluated its therapeutic effects on dyslipidemia and atherosclerosis in atherosclerotic mice. Methods Liposomal anti-PCSK9 vaccine was prepared viaattaching immunogenic peptide, termed Immunogenic Fused PCSK9-Tetanus (IFPT), on the surface of nanoliposome carriers by using DSPE-PEG-Maleimide lipid (L-IFPT). The L-IFPT formulation was adsorbed to Alum adjuvant (L-IFPTA+) and administrated subcutaneously four times with a bi-weekly interval in hypercholesterolemic C57BL/6 mice. Plasma levels of anti-PCSK9 antibody, plasma concentration of PCSK9 protein, effect of anti-PCSK9 antibody on PCSK9-LDLR interaction, protein levels of liver LDLR, lipid profile, as well as atherosclerotic lesion size and severity were measured in the vaccinated hypercholesterolemic mice. To determine immune safety, Inflammatory response was measured by evaluating IFN-γ and IL-10 producing splenic cells using ELISpot assay. Results L-IFPTA+vaccine promoted the high IgG antibody response against PCSK9 peptide in the hypercholesterolemic mice. L-IFPTA+-induced antibodies targeted plasma PCSK9 and thereby decreased plasma consecration of PCSK9, which was associated with the reduced PCSK9-LDLR interaction and the increased liver levels of LDLR protein. Inhibitory effect of L-IFPTA+vaccine was accompanied with a significant reduction of plasma levels of total cholesterol (TC), LDL-C, and VLDL-C. Interestingly, L-IFPTA+vaccine could considerably reduce atherosclerotic lesion size and intima to media thicknessin hypercholesterolemic mice. Long-term evaluation of hypercholesterolemic vaccinated mice showed that L-IFPTA+vaccine was able to promote a long-lasting anti-PCSK9 antibody titration, which was paralleled by a significant reduction of LDL-C over 16 weeks post prime immunization (Figure). Splenocytes isolated from vaccinated mice indicated the reduced IFN-γ producing cells and the elevated IL-10 producing cells, suggesting immune safety of liposomal anti-PCSK9 vaccine. Figure 1 Conclusions L-IFPTA+vaccine induced efficient anti-PCSK9 antibodies which could exert long-term therapeutic effect on hypercholesterolemia and atherosclerosis in mice, revealing a feasible vaccine-based approach for managing hypercholesterolemia and cardiovascular disease.

C679X loss-of-function PCSK9 variant lowers fasting glucose levels in a black South African population: A longitudinal study

AimsTo determine the longitudinal association of the loss-of-function (LOF) PCSK9 variants (C679X and A443T), proxies of PCSK9 inhibitor drugs, with LDL-C, fasting glucose and glycated hemoglobin. MethodsWe conducted a five year, longitudinal study, nested within the Prospective Urban and Rural Epidemiology study, among 737 apparently healthy, male and female black South Africans of the North West province. Genotyping of the C679X and A443T PCSK9 variants was achieved using Taqman assays from Applied Biosystems. Generalized estimating equations were used to determine longitudinal association of the A443T and C679X PCSK9 variants with LDL–C, fasting glucose and glycated hemoglobin. ResultsC679X and A443T variant carriers were associated with significant reductions in LDL-C of −0.98(−1.29, −0.67) mmol/L; p < 0.001) and −0.39(−0.57, −0.20) mmol/L; p < 0.001) respectively, compared to the non-carriers. Only C679X variant was independently associated with reductions in fasting glucose of −0.37 (−0.61, −0.13) mmol/L; p = 0.002) compared to non-carriers. However, the association of the selected variants with glycated hemoglobin were not significant. C679X and A443T carriers were associated with −0.07 (−0.23, 0.09) %; p = 0.400), 0.05 (−0.13, 0.22) %; p = 0.599) of glycated haemoglobin respectively. ConclusionOur results indicated that carriers of A443T and C679X variants exhibit sustained low LDL-C levels over 5 years and have varied effects on T2D biomarkers compared to non-carriers.

The Effect of Efpeglenatide on Lipid Profiles and Overall Metabolism in Patients with Type 2 Diabetes and Obese Patients without Diabetes

Once-weekly (QW), subcutaneous efpeglenatide (efpeg) is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) in development for T2D. Efpeg reduced blood glucose and body weight (BW) in Phase 2 trials in patients with T2D (EXCEED 203) and patients with obesity without diabetes (BALANCE 205; Table). To assess whether these effects were associated with benefits on lipids, the effects of efpeg QW on total cholesterol [TC], high [HDL-C], low [LDL-C], and very low density lipoprotein cholesterol [VLDL-C] and triglycerides [TG] were assessed in patients from these Phase 2 trials (VLDL-C measured in BALANCE 2only). In the 12-week EXCEED 203 study in patients with T2D, efpeg QW led to significant (p&amp;lt;0.05) reductions vs. placebo in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and BW (3-mg and 4-mg doses), and significant reductions in LDL-C and TG (4 mg only; Table). In the 20-week BALANCE 2study in nondiabetic patients with obesity, efpeg QW led to significant reductions vs. placebo in BW, HbA1c, FPG, TC, VLDL-C, TG (4-mg and 6-mg doses) and LDL-C and HDL-C (6 mg only). The safety profile of efpeg in both trials was consistent with GLP-1 RAs. These findings suggest that BW loss and glycemic effects with efpeg are accompanied by significant benefits on lipid profiles, providing an overall improvement in the abnormal metabolic state associated with T2D. Disclosure R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc. J. Kang: Employee; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. M.E. Trautmann: Consultant; Self; ProSciento. Stock/Shareholder; Self; Eli Lilly and Company. Consultant; Self; Hanmi Pharmaceutical, CeQur Corporation, Intarcia Therapeutics, Inc., Servier. M. Hompesch: Other Relationship; Self; Hanmi Pharmaceutical. K. Yoon: None. C.H. Sorli: Employee; Self; Sanofi.

Inclisiran for the treatment of dyslipidemia

ABSTRACTIntroduction: Dyslipidemia is one of the most important risk factors for cardiovascular disease. Insufficient reduction in LDL-C from existing therapies in patients at high risk of atherogenic cardiovascular disease is an unmet clinical need. Circulating PCSK9 causes hypercholesterolemia by reducing LDL receptors in hepatocytes.Areas covered: PCSK9 inhibition has emerged as a promising new therapeutic strategy to reduce LDL-C. Inclisiran, a novel, synthetic, siRNA molecule, inhibits PCSK9 synthesis in hepatocytes. Inclisiran targets intracellular PCSK9 synthesis specifically, resulting in a dose-dependent, long-term, significant reduction in LDL-C. Inclisiran has been well tolerated and safe, without severe adverse events so far. This review discusses current PCSK9 inhibitors and the results of phase I and II clinical trials of inclisiran.Expert opinion: Plasma PCSK9 enhances the degradation of LDL receptor, resulting in accumulation of LDL-C in the circulation. Current approaches with monoclonal antibodies sequester circulating PCSK9 but require frequent injections. Inclisiran inhibits translation of PCSK9 mRNA and thus switches off PCSK9 production and provides advantages over monoclonal antibodies with an infrequent dosing interval of twice a year to reduce LDL-C by over 50%. Ongoing studies will establish the long-term safety of inclisiran in patients with high cardiovascular risk and an elevated LDL-C.

An in vivo assessment of the cholesterol-lowering efficacy of Lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults.

Coronary heart disease (CHD) is one of the major causes of death and disability in industrialised countries, with elevated blood cholesterol an established risk factor. Total plasma cholesterol reduction in populations suffering from primary hypercholesterolemia may lower CHD incidence. This study investigated the cholesterol reducing capacity of Lactobacillus plantarum ECGC 13110402, a strain selected for its high bile salt hydrolase activity, in 49 normal to mildly hypercholesterolaemic adults. Primary efficacy outcomes included effect on blood lipids (total cholesterol (TC), low density lipoproteins (LDL-C), high density lipoproteins (HDL-C) and triacylgycerides (TAG), inflammatory biomarkers and occurrence/severity of gastrointestinal side effects to establish safety and tolerance of the intervention. Secondary outcomes included blood pressure, immune biomarkers, gut microbiota characterisation and metabonome changes. The study was run in a parallel, double blind, placebo controlled, randomised design in which the active group ingested 2x109 CFU encapsulated Lactobacillus plantarum ECGC 13110402 twice daily. Daily ingestion of the active treatment resulted in a statistically significant reduction in LDL-C in volunteers with baseline TC<5mM during the 0–12 week period (13.9%, P = 0.030), a significant reduction in TC in volunteers with baseline TC≥6mM in the 0–6 week period (37.6%, P = 0.045), a significant decrease in TAG (53.9% P = 0.030) and an increase in HDL-C (14.7%, P = 0.007) in the over 60 years population in the 6–12 week period. A statistically significant reduction in systolic blood pressure was also observed across the active study group in the 6-12-week period (6.6%, P = 0.003). No impact on gastrointestinal function and side effects was observed during the study. Similar to blood and urine metabonomic analyses, faecal metagenomics did not reveal significant changes upon active or placebo intake. The results of this study suggest that Lactobacillus plantarum ECGC 13110402 is a well-tolerated, natural probiotic, that may be used as an alternative or supplement to existing treatments to reduce cardiovascular risk.Trial registration: Clinical trials.gov NCT03263104

Indicaciones para el uso de los inhibidores de la PCSK9

The anti-PCSK9 monoclonal antibodies evolocumab and alirocumab represent a new group of non-statin hypolipidemic medications targeted at achieving significant reductions in LDLc, specifically in patients with high cardiovascular risk who do not attain the currently recommended LDLc goals, despite lifestyle changes and a maximum tolerated dose of statins in monotherapy or combined with ezetimibe. They are also directed to patients with intolerance, or a contraindication, to the use of statins, but who also have a high risk of cardiovascular events. The clinical evidence shows that the PCSK9 inhibitors are effective and safe medications, and that they reduce cardiovascular events.

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ALIROCUMAB IN HIGH CARDIOVASCULAR RISK PATIENTS WITH HYPERCHOLESTEROLEMIA NOT ADEQUATELY CONTROLLED WITH THEIR LIPID-MODIFYING THERAPY IN SOUTH KOREA AND TAIWAN

Background: Alirocumab (ALI), a fully human monoclonal antibody to PCSK9, has been shown to provide significant reductions in LDL-C. Data about its efficacy and safety in patients from South Korea and Taiwan is limited. Methods: Patients (n=199) with hypercholesterolemia at high cardiovascular risk

The effect of 8 weeks taichi chouan training and walking on cardiovascular disease biomarkers in old women’s

Abstract Background and aim: With regard to cardiovascular problems for older people due to lack of movement, The aim of the present study was redirected to an 8-week Tai Chi exercise on cardiovascular disease risk factors, including cholesterol (C), triglycerides (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C) and blood pressure in women elderly. Materials and methods: 30 subjects were selected living in a nursing home in Tehran in two groups randomly: Tai Chi and walking. On the first day and last day blood samples were taken from subjects to measure variables, and were compared between the two groups. Findings: Intragroup and intergroup results showed that both groups can have positive effects on lipid profile but changes in the tai chi group had significantly. Conclusion: Tai Chi had a significant reduction in LDL-C and significant increase in HDL-C, but the Tai Chi group had no significant effect in the levels of cholesterol and triglycerides.

How canola and sunflower oils affect lipid profile and anthropometric parameters of participants with dyslipidemia.

Background: Restricted intakes of saturated and trans-fatty acids and replacement with poly or monounsaturated fatty acids are emphasized in healthy diets. This study evaluates the effects of a six-month consumption of canola oil compared to sunflower oil on lipid profile and anthropometric parameters of people affected by dyslipidemia. Methods: This randomized controlled trial was conducted on 96 patients with dyslipidemia, who were randomly assigned into canola oil or the sunflower oil groups. The participants were instructed to record the contents of their daily meals, beverages, fruits, and snacks a day before treatment, at the second clinic visit, in the third month, and at the end of study (i.e., six months). Lipid profile and anthropometric parameters were compared between the two groups. Student t-test or Mann Whitney U test was used for statistical comparisons of variables between groups. Multivariate analysis was performed to adjust the confounding factor effects. Results: Of the enrolled participants, 44 (45.8%) were on sunflower oil diet and 52 (54.2%) on canola oil diet. We observed no change in anthropometric parameters and thus no significant difference between the two groups (p>0.05). Significant reductions in LDL-C (p<0.001), total cholesterol (p<0.001) and triglyceride levels (p<0.001), and significant elevation in HDL-C (p=0.008) were observed in canola oil group, as well as those who used sunflower oil. Conclusion: Dietary fats in the form of canola oil or sunflower oil effectively lower the serum cholesterol, LDL-C and triglyceride concentrations. They also result in an increase in serum concentration of HDL-C. These oils, however, did not modify general anthropometric parameters.

Low number of circulating CD34 positive cell is associated with greater progression of coronary calcium determined by MDCT

Objectives: The PEACH trial, which was a multicenter and randomized trial to evaluate the effects of lipid therapy on the progression of coronary calcium score (CCS), demonstrated that annual progression rate of Agatston score was 40% in whole patients irrespective of a significant reduction of LDL-C. The number of circulating CD34 positive cell was reported to be associated with cardiovascular risks. We examined the association the baseline number of CD34 positive cell and annual progression of CCS.

Efficacy and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients

Ezetimibe added to statin therapy further reduces LDL-C and clinical atherosclerotic cardiovascular disease compared to statin alone. However, the number of effective and safe oral agents for patients not at LDL-C goal is limited. In prior clinical trials, gemcabene reduced LDL-C and was generally well-tolerated in nearly 900 patients treated for up to 12weeks. To evaluate the LDL-C lowering and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients. This was an 8-week, double-blind, placebo-controlled, randomized, phase 2 study in men and postmenopausal women ≥18 and ≤65 years of age with LDL-C ≥130mg/dL (3.4mmol/L) while on low-intensity to high-intensity stable statin (the majority on moderate intensity) therapy. Sixty-six patients were randomized 1:1:1 to gemcabene 300mg, 900mg, or placebo QD. Gemcabene 300mg and 900mg produced a mean percent change in LDL-C of -23.4±4.7% (P=.005) and -27.7 ±4.3% (P<.001), respectively, vs -6.2 ±4.3% for placebo. The median percent change in CRP was -26.1% (P=.196) and -53.9% (P<.001) for gemcabene 300mg and 900mg, respectively, vs -11.1% for placebo. Gemcabene 300mg and 900mg were well-tolerated with no significant difference in AEs compared to placebo. Gemcabene as add-on to stable statin therapy demonstrated additional dose-dependent and statistically significant reductions in LDL-C of >20% and CRP >40% compared to placebo. The results support gemcabene-continued development for patients requiring LDL-C lowering beyond that provided by background statin therapy.

Association of ABCB1 (C3435T) and ABCC1 (G2012T) Polymorphisms with Clinical Response to Atorvastatin in Iranian Patients with Primary Hyperlipidemia.

Background:Atorvastatin is prescribed for the primary and the secondary prevention of coronary artery diseases. A wide variation in inter-individual statin response suggests that genetic differences may contribute to this variation. This study investigated the association of ABCB1 (C3435T) and ABCC1 (G2012T) polymorphisms with clinical response to atorvastatin in Iranian primary hyperlipidemic patients.Methods:Individuals (n=179) with primary hypercholesterolemia were enrolled, and peripheral blood samples were collected. Genotyping of two polymorphisms were performed by amplification refractory mutation system PCR.Results:Following four weeks of treatment, a significant reduction of LDL-C was observed in variant groups (CT+TT) of ABCB1 (P=0.018) and wild-type group (GG) of ABCC1 genes (P=0.029). Logistic regression analysis revealed a significant difference between male and female responses to 10 mg/day atorvastatin (P=0.004, odds ratio=0.2, CI 95%=0.06-0.6).Conclusion:Our finding indicated that these polymorphisms may be attributed to LDL-C serum levels in the primary hypercholesterolemia patients receiving atorvastatin.

Efficacy of alternate day versus daily atorvastatin in reduction of low density lipoprotein cholesterol: a prospective, randomized, open labelled, parallel group study

Background: Cardiovascular disease (CVD) is the leading cause of death in India and worldwide. Hypercholesterolemia plays a pivotal role in atherogenesis which gave rise to universally accepted cholesterol diet-CVD hypothesis. Statins are the most potent and commonly used drugs for treating hypercholesterolemia. With atorvastatin, because of the long lasting active metabolites, half-life of HMG-CoA reductase inhibition reaches 20 to 30 hours. Thus, it is conceivable that alternate-day atorvastatin treatment might be effective in maintaining the lipid-lowering efficacy.Methods: In this prospective, randomized, open labelled, parallel group study, 100 participants with serum low density cholesterol (LDL-C) level 100 mg/dL-190 mg/dL were recruited. Group A received 20 mg atorvastatin on alternate day and group B received 20 mg atorvastatin daily for 12 weeks. Follow up visits were scheduled at 6 and 12 weeks at which fasting serum LDL-C, serum TC, serum TG, serum HDL were estimated. Creatinine phosphokinase (CPK), aspartate transaminase (AST) and alanine transaminase (ALT) estimations were also done and participants were examined for occurrence of myalgia, jaundice or any other adverse effect.Results: A statistically significant reduction in LDL-C, TC, and TG was seen in both the groups when compared to baseline. At 12 weeks, the LDL-C reduction in alternate day atorvastatin group was 34.63% whereas in daily atorvastatin group, it was 38.75.The reduction in levels of TC in alternate day and daily atorvastatin group was 24.64% and 25.85% respectively. Both the regimens were well tolerated.Conclusions: The alternate-day dosing of atorvastatin is as efficacious and safe as that of its daily dosing.

Abstract 12468: Efficacy and Safety of Lomitapide in Japanese Patients With Homozygous Familial Hypercholesterolemia on Concurrent Lipid-Lowering Therapy

Introduction: Lomitapide is a microsomal triglyceride transfer protein inhibitor indicated as an adjunctive therapy for adults with homozygous familial hypercholesterolemia (HoFH). In a previous global Phase 3 study in non-Japanese patients with HoFH, lomitapide in combination with other lipid-lowering therapy resulted in a 50% reduction in LDL-C levels from baseline after 26 weeks of treatment. This open-label, multicenter, phase 3 study evaluated the efficacy and safety of lomitapide in adult Japanese patients with HoFH. Methods: Adult patients with HoFH added lomitapide to their maximally tolerated, stable lipid-lowering therapy. Lomitapide was initiated at 5 mg/day and escalated to each patient’s maximum tolerated dose (≤60mg/day) over 14 weeks. The primary endpoint was the mean % change from baseline in LDL-C at Week 26. Results: Nine patients (5 men, 4 women, mean age 50 [33-74] years) received lomitapide (mean dose 20 mg); 8 patients completed 26 weeks of treatment. Mean LDL-C was reduced from 199.3 mg/dL (95% CI: 148.6-250.0) at baseline to 117.9 mg/dL (95% CI: 70.2-165.6, last observation carried forward) at Week 26. Mean % LDL-C reduction was significant in patients with and without apheresis; significant reductions were also seen in key secondary endpoints (Table). A &gt;50% reduction in LDL from baseline was achieved by 5/9 (56%) patients. Gastrointestinal symptoms were the most common adverse event (diarrhea in 7/9 [78%] patients). Abnormal liver function tests were reported in 3/9 (33%) patients; 1 patient discontinued treatment after 22 weeks due to persistent liver enzyme elevations. There were no serious adverse events. Conclusions: The efficacy and safety of 26 weeks of lomitapide in Japanese patients were consistent with results in the global phase 3 study, including a significant reduction in LDL-C and no new safety signals. Treatment in the safety phase (Weeks 26-56) is ongoing.

What is the use of even lower LDL cholesterol by combination therapy? A critical viewpoint

The IMPROVE-IT study has demonstrated a significant reduction of LDL-C when ezetimibe was given in addition to statins. Although the number of strokes and MI was reduced after 7 to 10 years of this treatment, mortality was unaffected, however. Additive ezetimibe treatment can be recommended only, if a better or longer life has been proved - which is not the case.