Significant Reductions In LDL-C Research Articles

Short-Course High-Intensity Statin Treatment during Admission for Myocardial Infarction and LDL-Cholesterol Reduction-Impact on Tailored Lipid-Lowering Therapy at Discharge.

We hypothesized that a short-course high-intensity statin treatment during admission for myocardial infarction (MI) could rapidly reduce LDL-C and thus impact the choice of lipid-lowering therapy (LLT) at discharge. Our cohort comprised 133 MI patients (62.71 ± 11.3 years, 82% male) treated with atorvastatin 80 mg o.d. during admission. Basal LDL-C levels before admission were analyzed. We compared lipid profile variables before and during admission, and LLT at discharge was registered. Achieved theoretical LDL-C levels were estimated using LDL-C during admission and basal LDL-C as references and compared to LDL-C on first blood sample 4-6 weeks after discharge. A significant reduction in cholesterol from basal levels was noted during admission, including total cholesterol, triglycerides, HDL-C, non-HDL-C, and LDL-C (-39.23 ± 34.89 mg/dL, p < 0.001). LDL-C levels were reduced by 30% in days 1-2 and 40-45% in subsequent days (R2 0.766, p < 0.001). Using LDL-C during admission as a reference, most patients (88.7%) would theoretically achieve an LDL-C < 55 mg/dL with discharge LLT. However, if basal LDL-C levels were considered as a reference, only a small proportion of patients (30.1%) would achieve this lipid target, aligned with the proportion of patients with LDL-C < 55 mg/dL 4-6 weeks after discharge (36.8%). We conclude that statin treatment during admission for MI can induce a significant reduction in LDL-C and LLT at discharge is usually prescribed using LDL-C during admission as the reference, which leads to insufficient LDL-C reduction after discharge. Basal LDL-C before admission should be considered as the reference value for tailored LLT prescription.

Early initiation of PCSK9 inhibitor therapy versus placebo in patients with acute coronary syndrome: a systematic review and meta-analysis

Abstract Background In patients with stable atherosclerotic cardiovascular disease (ASCVD) and prior atherosclerotic events, PCSK9 inhibitors (PCSK9i) have shown a 50-60% reduction in LDL-C from baseline, on a background of high-intensity or maximally tolerated statin therapy, leading to a 15% relative reduction in the incidence of major adverse cardiovascular events. However, less is known about the impact of PCSK9i initiation acutely in the setting of an acute coronary syndrome (ACS). Purpose To assess the efficacy of early initiation of PCSK9i therapy in lipid parameters among patients presenting with ACS. Methods We performed a systematic review and meta-analysis comparing PCSK9i with placebo in the setting of ACS, added to guideline directed high-intensity or maximally tolerated statin therapy. Inclusion was restricted to randomized controlled trials (RCTs) with initiation of PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. The systematic review and meta-analysis followed Cochrane and PRISMA recommendations. Results Six RCTs with a total of 996 patients were included, of whom 503 (50.5%) received PCSK9i. Mean follow-up ranged from 4 to 52 weeks. Mean time from presentation to administration of first dose ranged from 3.6 hours to 6.5 days. LDL-C levels were significantly lower at follow-up in the PCSK9i group (mean difference [MD] -44 mg/dL; 95% CI -54.3 to -33.8 mg/dL; p&amp;lt;0.001; Figure 1A). Lp(a) was also significantly decreased with PCSK9i therapy (MD -24.0 nmol/L; 95% CI -43.0 to -4.9 nmol/L; p=0.01; Figure 1B). Similarly, total cholesterol (MD -49.2 mg/dL; 95% CI -59 to -39.3 mg/dL; p&amp;lt;0.001) and triglycerides (MD -19 mg/dL; 95% CI -29.9 to -8.2 mg/dL; p&amp;lt;0.001) were significantly reduced with PCSK9i therapy, respectively. HDL-C was marginally increased in this same group (MD 2.5 mg/dL; 95% CI 0.9 to 4.2 mg/dL; p=0.003). Conclusions In patients with ACS, early initiation of PCSK9i, in addition to statin therapy, leads to a significant reduction in LDL-C and Lp(a) as compared with placebo. Whether the differences in these lipoproteins translate into a reduction in clinical endpoints is yet to be determined.

Abstract 15073: Response to PCSK9 Inhibition in Homozygous Familial Hypercholesterolemia Patients is Variable in Different Regions of the World and According to Age

Background: Reductions in LDL-C with PCSK9-inhibition in HoFH subjects are highly variable even within populations with the same pathogenic variants. Whilst initial studies were done in HoFH patients of European decent, recent studies from India and other countries with novel pathogenic variants as well as studies in paediatric patients have shown substantially less response to PCSK9 inhibition. In the global phase 3 LIBerate-HoFH trial, we evaluated two different PCSK9 inhibitors, lerodacibep (LIB) 300 mg SC QM and evolocumab (EVO) 420 mg SC QM in genetically confirmed HoFH patients on stable background lipid lowering therapy. Methods: Eligible patients (age ≥10 years) were randomized to either LIB or EVO for 24 weeks (Period A) followed by an 8 week ‘washout’ and crossed over to the alternate drug for the next 24 weeks (Period B). In a post-hoc analysis, the mean reduction in average LDL-C with both drugs were evaluated according to various world regions and age. Results: Of 65 who entered Period A, 56 completed both periods: 31 in USA/Europe/Israel/South Africa; 15 in India and 10 in Turkey. Mean baseline LDL-C was 401 mg/dL; 55% were female and 19(34%) were adolescents aged &lt;18 years. For the total population, the mean (SE) reduction in average LDL-C was -9.6% (3.25) on LIB and -11.7% (3.65) on EVO (p=0.44, NS). LDL-C reductions varied considerably in different regions and response was poorer in the adolescent subjects. However, reductions in LDL-C of ≥15% were seen in 26.8% (n=15) with LIB and 37.5% (n=21) with EVO - Table. Conclusions: Reductions in LDL-C achieved with PCSK9-inhibition in HoFH subjects are highly variable and differ according to region and age. However, given the clinically significant reductions in LDL-C in 1/3 of patients including patients from India and Turkey with null/null or novel variants, PCSK9 inhibition should remain part of standard of care for HoFH patients who remain with elevated LDL-C levels despite treatment with statin and ezetimibe.

Abstract 13950: Real-World Effectiveness and Safety of Evinacumab in Pediatric and Adult Patients With Homozygous Familial Hypercholesterolemia: A Multi-Site US Perspective

Introduction: Homozygous familial hypercholesterolemia (HoFH) is an autosomal co-dominant disorder characterized by extreme elevations in LDL-C and early onset ASCVD. Unfortunately, patients with HoFH generally experience poor LDL-C lowering with standard lipid-lowering therapy and rarely achieve LDL-C goals. Evinacumab is a monoclonal antibody administered by monthly IV infusion that binds angiopoietin-like 3 and when added to standard lipid-lowering therapies lowers LDL-C by ~50% in clinical trials involving patients with HoFH. Real-world effectiveness and safety of evinacumab is unknown. Methods: We performed retrospective chart review to assess effectiveness and safety of evinacumab in patients with HoFH in clinical practice at six US academic medical centers. The primary efficacy endpoint was the percent change in LDL-C from baseline to first follow-up and to most recent follow-up after evinacumab initiation. Secondary efficacy endpoints were percent change in non-HDL-C, triglycerides, total cholesterol, HDL-C, and achievement of an LDL-C &lt;70 mg/dL. Adverse events were recorded. Results: Twenty-four patients (mean age 38 yrs; range 5-75) with HoFH were followed for a median of 63 weeks. Fifty percent were female, 66.7% had ASCVD, 87.5% were on a statin, 83.3% on ezetimibe, 66.7% on a PCSK9i, 24% on lomitapide, and 33.3% were undergoing lipoprotein apheresis. Significant reductions in LDL-C, non-HDL-C, total cholesterol, triglycerides, and HDL-C were observed both at first follow-up (4 weeks) and most recent follow-up (63 weeks) (p &lt; 0.001 for all) (Table). Significantly more patients achieved LDL-C &lt;70 mg/dL after evinacumab was added. No serious adverse events occurred and evinacumab was generally well-tolerated. Conclusions: Across six US academic medical centers, evinacumab was generally well-tolerated by patients with HoFH and lowered LDL-C by ~50%, consistent with results from clinical trials.

Abstract 15201: Obicetrapib as an Adjunct to Stable Statin Therapy Significantly Lowers LDL-C, Non-HDL-C, and Apolipoprotein B in Japanese Patients: Results From the Japan Phase 2 Study

Background: Obicetrapib is a selective CETP inhibitor that has been shown to reduce LDL-C, non-HDL-C, lipoprotein particles, and apolipoproteins when used as monotherapy, and in combination with ezetimibe, on background high-intensity statins. Previous studies of obicetrapib were conducted in predominantly Caucasian participants. There is a lack of clinical experience with obicetrapib when used in combination with stable statin therapy among Asian population. Objectives: This study was designed to fill the gap in clinical experience and to characterize the safety, efficacy profile of obicetrapib within the Asian population. Methods: The Phase 2 study is a trial of Japanese participants who had not achieved treatment goal in accordance with the 2022 Japan Atherosclerosis Society Guidelines and with LDL-C &gt;70 mg/dL or non-HDL-C &gt; 100 mg/dL and TG &lt; 400 mg/dL, while receiving stable statin background therapy. Participants were randomized 1:1:1:1 to obicetrapib 2.5 mg (n=25), obicetrapib 5 mg (n=25), obicetrapib 10 mg (n=26), or placebo (n=26). The primary endpoint was percent change in LDL-C from baseline to week 8. Key secondary endpoints included changes in ApoB, non-HDL-C, and HDL-C. Standard safety assessments were conducted. Results: Obicetrapib produced significant lowering of median LDL-C (45.8%, P&lt;0.0001), ApoB (29.7%, P&lt;0.0001), non-HDL-C (37.0%, P&lt;0.0001) and raising of HDL-C (158.9%, P&lt;0.0001). Placebo demonstrated median change of -0.9%, -0.4%, -0.4% and +5.2% for these parameters respectively. Obicetrapib was well tolerated with similar treatment emergent adverse events compared to placebo. There were no clinically significant changes in laboratory parameters, vital signs, or physical examinations in any treatment group. Conclusions: Similar to previous studies, obicetrapib 2.5 mg, 5 mg, and 10 mg resulted in significant reductions in LDL-C, ApoB, and non-HDL-C in the Asian population. All doses of obicetrapib were safe and well tolerated.

No Reduction in High Body Mass Index in Subjects at 1 Year Presenting With Acute Myocardial Infarction Treated With Percutaneous Coronary Intervention Despite Significant Reduction in LDL-C

No Reduction in High Body Mass Index in Subjects at 1 Year Presenting With Acute Myocardial Infarction Treated With Percutaneous Coronary Intervention Despite Significant Reduction in LDL-C

551 RAPID RELATIVE EFFECTIVENESS OF A NOVEL NUTRACEUTICAL FOR THE MANAGEMENT OF HYPERCHOLESTEROLEMIA: A MULTICENTER PRIMARY CARE EXPERIENCE IN A LARGE POPULATION OF PATIENTS AT LOW TO MODERATE CARDIOVASCULAR RISK

Abstract Backgroud In the last few years increasing evidence have reinforced the benefits of low-density lipoprotrein (LDL-C) levels reduction on cardiovascular outcome. Different targets have been suggested based on the cardiovascular risk (CVR). A goal of LDL-C less of 115mg/dL is desiderable for patients at low to moderate CVR according the current european guidelines. However, an high percentage of patients at low to moderate CVR are far from this target. Nutraceuticals are “food supplements” that may help to achieve this goal in this population. The aim of this retrospective analysis was to evaluate the effects of dietary supplementation with a novel nutraceutical formulation on plasma lipid levels in subjects with low to moderate hypercholesterolemia who are not on treatment with conventional drug and/or with other dietary supplements. Methods Adult patients with hypercholesterolemia were retrospectively selected from the database of participant family practitioners. All patients had a baseline evaluation already recorded, including family and medical history, physical examination, and blood test that included total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), C-reactive protein (CRP), and transaminases (AST and ALT) and have started a dietary supplementation with nutraceuticals. After this selection, a total of 504 patients under this novel nutraceutical (given 1 tablet daily at dinner) with blood test at 30-days already performed, were identified. Similarly, 108 subjects with comparable clinical features but not treated with any supplements were also selected. Results At 30-day of follow-up, the use of this novel dietary supplement was associated with significant reduction of LDL-C 124 ± 16 vs. 100 ± 13 mg/dL, p-value &amp;lt;0.001) and TC levels (210 ± 56 vs. 187 ± 60, p-value &amp;lt; 0.0001), in absence of a significant changes of transaminase levels (AST: 30 ± 6 vs. 30 ± 6 U/L, p-value 0.198; ALT: AST: 30 ± 6 vs. 30 ± 6 U/L, p-value 0.325) and in CRP (3.9 ± 1.5 vs. 3.9 ± 1.4 mg/dL, p-value 0.889). No side effects were reported in the database along to the observation period. Conclusion This novel nutraceutical formulation is an effective dietary supplement in obtaining a significant and early reduction of LDL-C in patients with hypercholesterolemia at low to moderate cardiovascular risk.

Effectiveness in the short-term of a novel nutraceutical for the management of hypercholesterolemia: an observational multicenter primary care experience

Purpose: Increasing evidence reinforces the benefits of reduction of low-density lipoprotein (LDL-C) levels on cardiovascular outcomes. Different targets are suggested based on cardiovascular risk (CVR). According to the current European guidelines, a goal of LDL-C≤ 115mg/dL is desirable for patients with low-moderate CVR. However, a high percentage of these patients are far from this target. Nutraceuticals are “food supplements” that may help to achieve this goal in this population. In this retrospective analysis, we evaluate the effects of dietary supplementation with a novel monacolin/berberine/bergamot nutraceutical formulation on plasma lipid levels of subjects with low-moderate hypercholesterolemia who are not treated with conventional drug or other dietary supplements. Patients and Methods:526 adult patients with hypercholesterolemia were retrospectively selected from the database of participant family practitioners according to prespecified criteria. All selected patients had a baseline and 30-day value of total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, and transaminases and have started a dietary supplementation with this novel nutraceutical. Similarly, 104 subjects with comparable clinical features but not treated with any supplements were also selected. Results:At 30-day, the administration of nutraceuticals was associated with a significant reduction of LDL-C (124 ± 14 vs. 100 ± 13 mg/dL, Δ 24.5mg, p-value &lt;0.0001) and TC levels (210 ± 56 vs. 187 ± 60, p-value &lt; 0.0001), in the absence of a significant change of transaminase levels. No side effects were reported in the database during the observation period. Conclusion: This novel nutraceutical is an effective dietary supplement to achieve a significant and early LDL-C reduction in patients with hypercholesterolemia at low-moderate CVR.Keywords:Cardiovascular Risk; Hypercholesterolemia; Nutraceuticals

Abstract 13703: Sex Differences on Cardiovascular Outcomes of Pcsk9-Inhibitors: A Meta-Analysis

Background: LDL-Cholesterol (LDLC) lowering therapies have been proven to significantly lower major adverse cardiovascular events (MACE) in patients with cardiovascular disease. Ideal LDL-C target levels are often not achieved using a high-dose statin and ezetimibe. The proprotein convertase subtilisin/kexin type-9 (PCSK-9) inhibitors can further reduce LDL-C and MACE, yet gender differences in LDL-C reduction remains unclear. We sought to determine if there are sex differences in efficacy outcomes of PCSK-9 inhibitors. Method: A comprehensive literature search was performed, and ongoing studies were identified using ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We used a PRISMA, Preferred Reporting Items for a Review and Meta-analysis and RevMan version 5.4 software to conduct a meta-analysis, heterogeneity test, and sensitivity analysis on the included studies. We established the significance level for all outcomes at a P-value of &lt;0.05. Statistical heterogeneity was identified through forest plots and a standard Chi-squared test with a significant level of p&lt;0.1. The extent of heterogeneity was based on the I 2 statistic, wherein a value of more than 50% was interpreted as substantial heterogeneity. Fixed-effects analysis was applied in this meta-analysis. Results: There was a significant reduction in MACE in PCSK9 inhibitor arm vs. placebo in both males (HR 0.85, 95% CI 0.80 to 0.91, p&lt;0.0001, and females (HR 0.86, 95% CI 0.76 to 0.96, p=0.009) (Figure). Furthermore, there was a similar significant reduction in LDLC with PCSK-9 inhibitors compared to placebo and ezetimibe for both sexes. Lastly, there was a significant reduction in LDL-C seen in both sexes when analyzed as to the frequency of PCSK9 inhibitor administration and the type of PCSK9 inhibitor given. Conclusion: This meta-analysis found no sex differences and similar efficacy in women and men in reducing MACE using PCSK-9 inhibitors.

Effects of short-term pistachio consumption before and throughout recovery from an intense exercise bout on cardiometabolic markers

Although pistachios have been shown to improve cardiometabolic biomarkers in diseased and at-risk populations, less research has been conducted on young, healthy individuals. Furthermore, some but not all research indicates that exercise acutely improves cardiometabolic markers; however, it remains unclear as to why outcomes vary among studies. This research evaluated secondary aims of a study designed to assess the impacts of pistachios on recovery from vigorous eccentrically-biased exercise. Here we examined the short-term (two weeks) effects of two different doses (1.5 oz/d and 3.0 oz/d) of pistachios and a water-only control on the biomarkers of metabolic health in young adult men. This was followed by daily blood collection for three consecutive days after a 40-min downhill run. Twenty-seven participants completed each of three conditions in a counterbalanced randomized order. Plasma biomarkers (lipid profile, glucose, and insulin) were measured at the end of each 2-week feeding period immediately before the exercise bout and again 24, 48, and 72 h thereafter. Two weeks of pistachio consumption failed to elicit changes in any biomarker (p < .05).. Exercise reduced LDL-cholesterol at the end of the recovery period; however, positive effects were limited to when subjects were consuming the higher dose of pistachios. Follow up t-tests revealed significant reductions in LDL-C in the high dose group at 72-H compared to that at 0-H (8.2 ± 19.4; p < .04), 24-H (8.0 ± 18.6; p < .04), and 48-H (9.3 ± 15.8; p < .005) post exercise within the same trial. Overall, in healthy young men with normal blood lipid and glucose metabolism, little effect of either pistachios or intense exercise on cardiometabolic risk indicators was detected. More research is needed to determine the influence of usual diet consumption on outcomes following an acute exercise bout.

Alirocumab reduces total coronary plaque burden in patients with familial hypercholesterolaemia and no previous clinical atherosclerotic disease

Abstract Background It is well known that statins, ezetimibe and other lipid lowering treatments such as Evolocumab (PCSK9-Inhibitor) reduce cardiovascular events by decreasing LDL-cholesterol (LDL-C) levels and slowing the progression of coronary atherosclerosis. Nevertheless, cardiovascular (CV) risk remains. Alirocumab, a PCSK9 inhibitor has demonstrated a reduction in cardiovascular events but its relationship with coronary atherosclerosis reduction has not been adequately demonstrated. Purpose The ARCHITECT trial sought to determine whether Alirocumab 150 mg/2 weeks is able to stop or reverse coronary atherosclerosis progression, by assessing coronary plaque burden (CPB) by serial multidetector computed tomography (MDCT). Methods A total of 104 patients with molecularly characterized heterozygous familial hypercholesterolaemia (FH) without clinical cardiovascular disease were enrolled in this trial. Patients had to have CPB &amp;gt;30% as documented by MDCT, be on maximum tolerated statin therapy with or without ezetimibe and LDL-C &amp;gt;100 mg/dL. Patients underwent a MDCT at enrollment and after 18-month treatment with alirocumab and they were analyzed by means of QAngio CT (Medis medical imaging system, the Netherlans). The pre-specified primary endpoint was change in CPB. Results Median age was 53.3 (46.2–59.4) years (54, 51.9% woman). Median LDL-cholesterol was 138.9 mg/dL. There was a significant reduction in the primary endpoint as Alirocumab reduced CPB from 34.6 (32.9–36.8)% to 30.4 (27.4–33.4)%. Significant reductions in LDL-C (67%) and atherosclerotic plaque volume were also found. Plaque regression as estimated by CPB was found in 91 (87.5%) patients. Main resuts may be found in figure 1. Conclusions Alirocumab demonstrated significant regression of CPB on MDCT over 18 months. ARCHITECT provides crucial mechanistic clues on coronary plaque behavior under the use of Alirocumab and its results could link and explain ODYSSEY-OUTCOMES results. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi

Young Age Onset Multivascular Pathology in a Patient with Severe Dyslipidemia: an Incidental Case or a Particular Type of Familial Hypercholesterolemia?

Abstract Familial hypercholesterolemia (FH) is a genetic disorder that affects about 1 in 250 people and increases the likelihood of having coronary heart disease at a younger age. We present the case of a 55-year-old patient, known with inferior and anterior myocardial infarction treated by percutaneous coronary intervention and coronary artery bypass grafts, Leriche syndrome, aortic abdominal aneurysm, and bilateral renal stents—pathologies with onset at a young age—who was admitted for fast-paced palpitations, accompanied by increased fatigue. The coronarography did not reveal any acute lesions, but the presence of ventricular tachycardia at admission required the implantation of a cardiac defibrillator. Since the patient presented with early onset severe systemic atherosclerosis, with a lipid profile dominated by hypo-HDL, doubled by an apolipoprotein A1 deficiency, we considered the diagnosis of familial hypercholesterolemia. Due to the high-risk profile, the association between a statin and a PCSK9 inhibitor was initiated at discharge. At the 1-month follow-up control, a significant reduction of LDL-C has been achieved, with a simultaneous increase of HDL-C serum levels.

Effect on the cardiovascular independent risk factor lipoprotein(a) in overweight or obese PCOS patients with ethinyl-estradiol/drospirenone alone or plus orlistat

Objective This study aimed to assess the effect on the cardiovascular independent risk factor Lipoprotein(a) [Lp(a)] in overweight or obese polycystic ovary syndrome (PCOS) patients with ethinyl-estradiol/drospirenone (EE/DRSP) alone or plus orlistat. Methods In this randomized controlled prospective study, 66 PCOS patients with overweight or obesity were matched according to age and BMI. All participants were randomly divided into two groups to receive EE/DRSP plus Orlistat (n = 33) or EE/DRSP alone (n = 33) for 3 months. Changes in cardiovascular risk factors including Lp(a), CRP, LDL-C, anthropometric assessments, variations in sex hormones related parameters, and in glucolipid metabolic index were evaluated after the intervention. Results Lp(a) and CRP were significantly decreased at 3 months only in the EE/DRSP plus Orlistat group. There were significant reductions in LDL-C, weight, BMI, waist circumference (WC), body fat percentage (BFP), FT in both groups compared to baseline. However, these reductions were significantly greater in EE/DRSP plus Orlistat group. The levels of HDL-C, TG, and SHBG significantly increased, while TT and LH significantly decreased in both groups over time. TC, FINS, FPG were not significantly changed in both groups after the intervention. Conclusions This is the first study found that EE/DRSP plus Orlistat could significantly decrease Lp(a) in overweight or obese PCOS patients. This result can be assessed as particularly important, because Lp(a) is well-known as an independent risk factor predicting an increased risk of cardiovascular diseases (CVDs).

Safety and Efficacy of Bempedoic Acid in Statin-Intolerant Patients

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Bempedoic acid is a first-in-class citrate lyase inhibitor that reduces atherogenic lipoproteins. There is limited data on the incidence of muscle-related adverse effects in statin-intolerant patients treated with bempedoic acid. <h3>Objective/Purpose</h3> To determine the effect of bempedoic acid on atherogenic lipoproteins in patients not on statins and whether statin-intolerant patients experience muscle-related adverse effects. <h3>Methods</h3> We performed a systematic review and meta-analysis of all published studies reporting the outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia who were not on statins. All studies were included in the analysis of the lipoprotein effects (n=6), whereas only studies of statin-intolerant patients were included in the analysis of muscle-related adverse effects (n=4). <h3>Results</h3> The meta-analysis included 1,084 patients not on statins: 792 on bempedoic acid, and 292 on placebo. Four studies included only statin-intolerant patients (n=847): 629 on bempedoic acid and 218 on placebo. During a median follow-up of 12 weeks (range 4-24 weeks), bempedoic acid produced significant reductions in LDL-C (mean difference (MD) -25.7%, p<0.001), non-HDL cholesterol (MD -21.2%, p<0.001), and total cholesterol (MD -16.7%, p<0.001), compared to placebo with a similar risk of muscle-related adverse events (odds ratio (OR) 0.82, p=0.37), including myalgia (OR 0.71, p=0.32), muscle spasm (OR 1.08, p=0.84), weakness (OR 0.47, p=0.21), and muscle pain (OR 1.10, p=0.81). <h3>Conclusions</h3> Bempedoic acid decreases atherogenic lipoproteins in patients not taking statins and does not increase the incidence of muscle-related adverse events in statin-intolerant patients.

341 Observational multicentre study on effectiveness and tolerability of Alirocumab in real world, the OMERO study: interim data from the first 699 patients

Abstract Aims OMERO is a prospective study, aimed to assess the long-term effectiveness, tolerability, and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9-i), in the real life in Italy. The study is planned to include 800 patients, from 40 Italian sites, treated with alirocumab on top of standard lipid lowering therapy. Methods and results This analysis concerns 699 (out of 800) patients with all data available: 65.5% male; mean age 60.6 ± 11.09 years; 29.6% with HeFH in primary prevention; 70.4% in secondary prevention (with/without HeFH). Before ALI administration, 461 patients (66%) were treated with statins while 231 (33%) reported statin intolerance, that resulted in the statin discontinuation. Mean baseline LDL-C was 161.5 ± (53.07) mg/dl. Based on clinical judgement, ALI was initially prescribed at 75 mg Q2W dosing regimen in 60.80% of participants, whereas the remainder received 150 mg Q2W. At V1 57 patients (89.06%) switch from 75 mg Q2W to 150 mg Q2W and 7 patients (10.94%) from 150 mg Q2W to 75 mg Q2W. LDL-C level reduction from baseline (before ALI administration) to 6 months from the study enrolment (V1), was −45% (V1: mean LDL-C was 73.5 ± 45.70 mg/dl). LDL-C levels at V1 by participant category are shown in Figure 1. The rate of patients with at least one adverse event was 25.6% (of which SAE 7.4%); the rate of patients with at least one related adverse reaction to treatment was 3.8% none of them were serious. Conclusions OMERO confirmed in clinical practice the results observed in trials: a significant reduction of LDL-C was observed with ALI 75/150 mg Q2W in participants at high CV risk with or without HeFH. ALI was generally well tolerated.

Efectividad y seguridad del tratamiento con iPCSK9 en vida real: experiencia de tres hospitales asturianos

BackgroundInhibitors of proprotein convertase subtilisin/kexin type9 (PCSK9 inhibitors) are a treatment option for those patients with familial hypercholesterolemia or in secondary prevention who do not reach the LDL-C target with other therapeutic measures. The aim of this study is to assess the effectiveness and safety of these drugs. MethodsRetrospective, multicentric, descriptive study. We collected data from all patients that have started PCSK9 inhibitors treatment in three hospitals in Asturias since the beginning of its use in 2016. We analysed changes in lipid profile with PCSK9 inhibitors and its side effects. ResultsWe registered 98 patients, 75 of them affected by familial hypercholesterolemia (FH) and 23 unaffected. Two months after the beginning of PCSK9 inhibitors treatment, a 61% reduction rate in LDL-C in patients with FH and 52% in those without this condition was observed. This statistically significant reduction remained stable during follow-up. A significant decrease in total cholesterol was observed, without significant changes in HDL-C and triglycerides. 96% of patients had no complications. ConclusionsPCSK9 inhibitors are safe drugs that rapidly achieve significant reductions in LDL-C after the beginning of treatment, which are maintained over time. Hence, the use of PCSK9 inhibitors is an alternative for the control of LDL-C in those patients in which the LDL-C target is not reached with other therapeutic measures.

Effect of L-carnitine supplementation on lipid profile and apolipoproteins in children on hemodialysis: a randomized placebo-controlled clinical trial

Cardiovascular disease (CVD) is the leading cause of death in children with chronic kidney disease (CKD) and accounts for 40% of all deaths among pediatric patients with stage5 chronic kidney disease (CKD5). Dyslipidemia is common in children with CKD and is considered one of the major causes of CVD in these patients. As carnitine plays a key role in lipid metabolism and because plasma levels are reduced in hemodialysis patients, the aim of this study was to determine the effects of L-carnitine supplementation on serum lipid profiles, apolipoproteins, and free carnitine (FC) levels. A total of 30 children on hemodialysis (6-18 years) were enrolled and 24 completed the study. Twelve patients received 50 mg/kg/day L-carnitine, while the other 12 patients received placebo for 10 weeks. Serum FC, total cholesterol (TC), LDL-C, HDL-C, TG, Apolipoprotein B (ApoB), and Apolipoprotein A1 (ApoA1) were determined at the baseline and after the intervention. One-way repeated measures analysis was used to evaluate the effects of L-carnitine supplementation. Oral L-carnitine supplementation led to decreased ApoB levels and ApoB/ApoA1 ratio, but these changes were not significant compared to placebo. Meanwhile, L-carnitine supplementation significantly reduced serum LDL-C and TC and increased serum FC compared to placebo. No significant changes were observed in serum TG and HDL-C levels. Given the significant reduction in LDL-C and TC levels, L-carnitine supplementation had positive effects on improving hyperlipidemia in children receiving hemodialysis. For more decisive results, studies with longer duration of L-carnitine therapy on children receiving hemodialysis with significant dyslipidemia are recommended. We registered the present trial in the Iranian Registry of Clinical Trials website (available at: http://www.irct.ir , identifier: IRCT20170202032367N2).

Isomers of guggulsterone in hyperlipidemia

Hyperlipidemia is one of the major issues which results in serious cardiovascular complications. Plant-based medicinal products have been commonly used for several chronic disorders. Guggulsterone isomers is proven to be cholesterol lowering activity which is a major bioactive compound present in Commiphora mukul and Commiphora wighti . On the basis of existing clinical evidence, it seems that guggulsterone is much helpful in reduction of Low-density lipoprotein levels. On the other hand, it is important to consider clinical pharmacokinetics of Guggulsterone isomers to create a definitive decision in this context. • Guggulsterone isomer is one of the major bioactive compounds present in Commiphora species. • Guggulsterone antagonizes the Farnesoid X Receptor, which involves the conversion of cholesterol into bile acids. • Long term administration of Guggulsterone isomers shows a significant reduction of LDL-C.

Impact of Diet on Plasma Lipids in Individuals with Heterozygous Familial Hypercholesterolemia: A Systematic Review of Randomized Controlled Nutritional Studies.

Background: Conclusive data on the effectiveness of dietary interventions in heterozygous familial hypercholesterolemia (HeFH) management are unavailable. Whether this is due to a true lack of effects or biases in intervention designs remains unsettled. We systematically assessed the impact on LDL-C of published dietary randomized controlled trials (RCTs) conducted among individuals with HeFH in relation to their design and risk of bias. Methods: We systematically searched PubMed, Web of Science, and Embase in November 2020 to identify RCTs that assessed the impact of: (1) food-based interventions; (2) dietary counseling interventions; or (3) dietary supplements on LDL-C in individuals with HeFH. We evaluated the risk of bias of each study using the Cochrane Risk of Bias 2 method. Results: A total of 19 RCTs comprising 837 individuals with HeFH were included. Of those, five were food-based interventions, three were dietary counseling interventions and 12 were dietary supplement-based interventions (omega-3, n = 3; phytosterols, n = 7; guar gum, n = 1; policosanol, n = 1). One study qualified both as a food-based intervention and as a dietary supplement intervention due to its factorial design. A significant reduction in LDL-C levels was reported in 10 RCTs, including eight dietary supplement interventions (phytosterols, n = 6, omega-3, n = 1; guar gum, n = 1), one food-based intervention and one dietary counseling intervention. A total of 13 studies were judged to have some methodological biases in a way that substantially lowers confidence in the results. Studies at low risk of biases were more likely to report significant reductions in LDL-C concentrations, compared with studies at risk of bias (chi-square statistic: 5.49; p = 0.02). Conclusion: This systemic review shows that the apparent lack of effectiveness of diet manipulation in modulating plasma levels of LDL-C among individuals with HeFH is likely due to biases in study designs, rather than a true lack of effects. The likelihood of reporting significant reductions in LDL-C was associated with the concurrent risk of bias.

The effect of meal frequency on biochemical cardiometabolic factors: A systematic review and meta-analysis of randomized controlled trials

Although several randomized controlled trials (RCTs) have supported the beneficial effects of higher meal frequency (MF) on cardiometabolic risk factors, the putative effects of higher MF on health remain inconclusive. This study systematically reviewed the evidence from RCTs of the effect of higher compared with lower MF on the blood lipid profile, glucose homeostasis, and adipokines. PubMed, Scopus, ISI Web of Science, and the Cochrane database were searched up to October 2020 to retrieve relevant RCTs. A DerSimonian and Laird random effects model was used to pool mean differences and 95% CI for each outcome. The quality of studies and evidence was assessed through standard methods. Twenty-one RCTs (686 participants) were included in this meta-analysis. Overall results showed a significant improvement in total cholesterol [weighted mean difference (WMD)=-6.08mg/dl; 95% CI:-10.68,-1.48; P=0.01; I2=88%], and low-density cholesterol (LDL-C) (WMD=-6.82mg/dl; 95% CI:-10.97,-1.60; P=0.009; I2=85.7%), while LDL-C to high-density cholesterol ratio (LDL-C: HDL-C) increased (WMD=0.22; 95% CI: 0.07, 0.36; P=0.003; I2=0.0%) in higher MF vs. lower MF. No significant effects were found on measures of glycemic control, apolipoproteins-A1 and B, or leptin. In subgroup analyses, higher MF significantly reduced serum triglyceride (TG), and increased HDL-C, compared with lower MF in interventions>12 weeks, and decreased serum TC and LDL-C in healthy participants. A significant reduction in LDL-C also was observed in studies where the same foods given both arms, simply divided into different feeding occasions, and in feeding studies, following higher MF compared to lower MF. Our meta-analysis found that higher, compared with lower MF may improve total cholesterol, and LDL-C. The intervention does not affect measures of glycemic control, apolipoproteins-A1 and B, or leptin. However, the GRADE ratings of low credibility of the currently available evidence highlights the need for more high-quality studies in order to reach a firm conclusion.