Efficacy Of Lipid-lowering Therapy Research Articles

Management of children with heterozygous familial hypercholesterolemia worldwide: a meta-analysis

Abstract Background HeFH is one of the most frequent monogenic disorders in the world, leading to premature ASCVD. Purpose The aim of this meta-analysis was to evaluate the efficacy and safety of lipid lowering therapy (LLT) and achievement of LDL-C goal in heFH children. Methods The main endpoint was efficacy of goal achievement for LDL-C and other lipid parameters: total cholesterol [TC], triglycerides [TG], high density lipoprotein cholesterol [HDL-C], apolipoprotein B [apo B] and lipoprotein(a) [Lp(a)]), and the LLT safety (adverse events [AEs], including endocrine function, and growth indices). The secondary endpoint was an effect of LLT on attainment of LDL-C goal treatment (<3.5 mmol/L/130 mg/dL). Results A total of 41 studies with 4667 pediatric patients at mean age 12.08±2.4 years were included. At median follow-up of 18.8 months, the group on LLT had significantly higher mean reductions of TC, LDL-C, TG, and increased HDL-C compared to control (-1.75 [-67,7 mg/dl], -1.84 [-71.2 mg/dl], -0.11 [-9.74 mg/dl], 0.08 mmol/L [3.1 mg/dl], respectively, p<0.001 for all). In the subgroup analysis according to different types of LLT we observed a significantly higher mean reduction of LDL-C by statin combined with ezetimibe treatment, followed by PCSK9 inhibitors, statins in monotherapy, and monotherapy with ezetimibe (-2.48 [-95.9 mg/dl], -2.16 [-83.5 mg/dl], -2.03 [-78.5 mg/dl], and -1.50 mmol/L [-58 mg/dl], respectively, test for overall effect: p<0.001). The pooled LDL-C was reduced by 33.44% (-2.14 mmol/L [-82.8 mg/dl], p<0.001) and failed to reach the goal treatment (<3.5 mmol/L) by 12.6% (95%CI, 12.4 – 12.9%). 38.7% of children achieved the LDL-C goal, 23.9% fell short by up to 10%, 10.7% experienced moderate failure (were over the LDL-C target between >10-20%), and 26.7% failed by more than 20% to reach the LDL-C target. When comparing different regions, only Sweden and Greece achieved the LDL-C goal <3.5 mmol/L in the follow-up, followed by the Netherlands, Norway, Poland, USA, UK, France, Spain, Belgium, and Austria (with the following additional required LDL-C reduction to be on the goal: 2.2%, 3.4%, 3.5%, 8.9%, 10.2%, 11.2%, 11.2%, 15%, 19.4%, respectively). For other investigated countries over 20% mean LDL-C reduction was required. All parameters related to endocrine function and demographic indices were unaffected by LLT therapy (p>0.05). The adverse events were not reported significantly higher when compared to the control and the prevalence of therapy discontinuation was only 0.8%. Conclusions Despite the efficacy of LLT in children with HeFH and the low occurrence of discontinuation-related adverse events, achieving LDL-C treatment goals was relatively rare, with large differences between the investigated countries. These results underscore the importance of considering early combination therapy of statins and ezetimibe, and PCSK9 inhibitors (if available) to attain LDL-C goals effectively.Lipoproteins reduction with LLT.Goal achievement and therapy safety.

Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events

Abstract Background Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe, bempedoic acic, and proprotein convertase subtilisin/kexin type 9 (PCSK-9) (synthase-) inhibitors allow for the reduction in LDL-cholesterol in addition to statin therapy. Purpose We aimed to perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome. In specific, we evaluated the potential influence of duration of follow-up on the association with mortality endpoints. Methods We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe, bempedoic acid, Bococizumab, Alirocumab, Evolocumab, Inclisiran in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of August 2023, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were : "Bempedoic Acid" or "Bococizumab" or "Alirocumab" or "Evolocumab" or "Ezetimibe" or "Inclisiran" and "statin" and "cardiovascular events". Results A total of 123,785 patients from 15 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, ODYSSEY LONG TERM, EWTOPIA 75, PACMAN-AMI, RACING, SIPRE I, SPIRE II, OSLER-1 and OSLER-2, CLEAR HARMONY, CLEAR OUTCOMES, CLEAR SERENITY, CLEAR WISDOM) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 19% risk reduction in cardiovascular events (OR [95%CI]: 0.81 [0.75; 0.86]). Effect sizes were similar for myocardial infarction (0.81 [0.74; 0.89]) and even more pronounced for ischemic stroke (0.77 [0.70; 0.84]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.99 [0.93; 1.04]). Stratifying by follow-up duration of < vs. ≥ 3 years, no improvement in all-cause mortality was observed in both groups (<3 years: 1.04 [0.93; 1.17]; ≥3 years: 0.97 (0.88; 1.06). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Conclusion Intensified LDL-lowering therapy with ezetimibe, bempedoic acic or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. A potential survival benefit was also not observed in studies with follow-up duration of ≥ 3 years.

Contradictions in traditional ideas about atherosclerosis and the efficacy of lipid-lowering therapy. Promising directions

The review presents contradictory results from numerous clinical and epidemiological studies, giving reason to doubt the indisputability of ideas about the primary role of low-density lipoprotein (LP) cholesterol in atherogenesis and the efficacy of lipid-lowering therapy. The latter clearly demonstrates the absence of the expected clinical effect in reducing cholesterol levels after surgical correction of lipid metabolism (ileal bypass surgery) or a very modest effect when using drugs devoid of pleiotropic properties. This circumstance finds an explanation in the fact that, according to modern concepts, only modified LP are the molecular substrate of the pathophysiological process at all stages of atherosclerosis development. Native (intact) LP, the concentration of which in the blood does not correlate with the level of modified forms, are not included in the pathogenesis of atherosclerosis. Consequently, the presence of native LP in the blood does not give a true picture of the activity of the atherosclerotic process. Based on the above, in the treatment of atherosclerosis, it should be considered justified not so much to further improve methods of lipid-lowering effects on the body, which do not have a sufficiently reliable evidence base of clinical effect, but to search for means that prevent the generation of atherogenic, modified LP. In this regard, taking into account the important role of systemic inflammation in the pathogenesis of atherosclerosis, the synthesis and clinical use of safe anti-inflammatory drugs, as well as the development and implementation of methods aimed at eliminating the causes of systemic inflammation, should be considered promising.

Dyslipidaemia in patients with chronic kidney disease - a neglected cardiovascular risk factor.

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). In addition, CKD itself is a coronary artery disease equivalent due to its atherogenic potential. Despite the role of CKD in ASCVD and recommendations to control lipid levels aggressively, landmark lipid studies have often excluded patients with advanced CKD. Furthermore, there is a scarcity of data on the use and efficacy of lipid-lowering therapy (LLT) in those with CKD in South Africa (SA). To determine the prevalence and control of dyslipidaemia in a cohort of SA patients with CKD. A retrospective, cross-sectional observational study of 250 patients with CKD attending the Charlotte Maxeke Johannesburg Academic Hospital renal clinic from 1 July 2019 to 31 July 2020 was carried out. Lipograms, the use of LLT and achievement of target lipid levels were examined. The median (interquartile range) age of this cohort was 58 (46 - 69) years; 50.4% were males and 64.4% black African. Dyslipidaemia was prevalent in 83.6% (n=209) of patients. A total of 169 (67.6%) patients were on LLT, and of these only 28 (16.6%) achieved the recommended low-density lipoprotein cholesterol (LDL-C) target. Of those not on LLT, 51 (63%) were eligible for LLT and almost all were classified as either very high risk (64.2%) or high risk (28.4%) for ASCVD. Of those on LLT, all were on statin therapy, of which simvastatin at a mean dose of 20 mg daily was the most commonly prescribed LLT. This cohort comprised a large proportion of patients classified as high or very high risk for ASCVD. Despite this, the use of LLT was inadequate, and <20% of patients were at target LDL-C levels. These data suggest a greater need for awareness of initiating LLT to achieve recommended target LDL-C levels in patients with CKD.

Effects of Lipid Lowering Therapies on Vulnerable Plaque Features: An Updated Narrative Review of the Literature.

The clinical evidence on the efficacy of lipid lowering therapy in patients with coronary artery disease (CAD) is unequivocally established. However, the effects of these therapies on plaque composition and stability are less clear. The use of intracoronary imaging (ICI) technologies has emerged as a complement to conventional angiography to further characterize plaque morphology and detect high-risk plaque features related to cardiovascular events. Along with clinical outcomes studies, parallel imaging trials employing serial evaluations with intravascular ultrasound (IVUS) have shown that pharmacological treatment has the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved. Subsequently, the introduction of high-intensity lipid lowering therapy led to much lower levels of low-density lipoprotein cholesterol (LDL-C) levels than achieved in the past, resulting in greater clinical benefit. However, the degree of atheroma regression showed in concomitant imaging trials appeared more modest as compared to the magnitude of clinical benefit accrued from high-intensity statin therapy. Recently, new randomized trials have investigated the additional effects of achieving very low levels of LDL-C on high-risk plaque features-such as fibrous cap thickness and large lipid accumulation-beyond its size. This paper provides an overview of the currently available evidence of the effects of moderate to high-intensity lipid lowering therapy on high-risk plaque features as assessed by different ICI modalities, reviews data supporting the use of these trials, and analyse the future perspectives in this field.

Adherence to lipid-lowering therapy and reaching treatment goals in youth seen in a preventive cardiology clinic.

The efficacy of lipid-lowering therapy in reducing cardiovascular disease in adults is well-established. Unfortunately, it is also well-established that adults have inadequate adherence to lipid-lowering therapy, which is associated with increased costs and mortality. However, the adherence patterns of youth prescribed lipid-lowering therapy is not well-described. We analyzed data that was prospectively collected from patients <27 years-old who were referred to a large regional preventive cardiology clinic from 2010 to 2017. Adherence to lipid-lowering therapy was self-reported at the patient's most recent clinic visit and categorized as either adequate adherence (≥80%) or inadequate adherence (<80%). We compared adherence rates by demographic factors, class of lipid-lowering therapy, length of time on lipid-lowering therapy, family history, lipid parameters, and laboratory measures of adverse effects. In our cohort, we had 318 patients prescribed a lipid-lowering medication over a seven-year period. Of those, 235 (75%) had adequate adherence. Those with adequate adherence had an improved LDL-C (123mg/dL [standard deviation (SD) 32.3] vs. 167mg/dL [SD 50.4], p<0.05), total cholesterol (198mg/dL [49.5] vs. 239mg/dL [SD 53.2]), and non-HDL-C (148mg/dL [SD 38.7] vs. 193mg/dL [SD 43.9]). In addition, patients with adequate adherence were more likely to reach goal LDL-C of <130mg/dL than those with inadequate adherence (130 vs. 25, p<0.01). The relationship between LDL-C and adherence remained statistically significant after controlling for age, gender, and the length of time on therapy (β=-0.66, p<0.01). Adherence level did not differ by gender, class of lipid-lowering therapy, length of time on lipid-lowering therapy, or presence of a family history of an atherosclerotic event. The findings were similar when we only analyzed those prescribed a statin. Self-reported adherence to lipid-lowering therapy in youth is excellent and was associated with achieving goal LDL-C goals. Obtaining adherence data from patients may help more patients reach LDL-C goals.

Underrepresentation of ethnic and regional minorities in lipid-lowering randomized clinical trials: a systematic review and meta-analysis.

The efficacy of lipid-lowering therapies (LLT) among different ethnicities and regions remains unclear. We aimed to assess cardiovascular event reductions associated with LLT according to ethnicity and region in previously published randomized clinical trials (RCTs). Medline, EMBASE and Cochrane CENTRAL were searched for RCTs of statins, ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors comparing intensive versus less intensive low-density lipoprotein cholesterol (LDL-C) lowering. The primary endpoint was major adverse cardiovascular events (MACE) defined as the composite of cardiovascular mortality, myocardial infarction, stroke and revascularisation. Random effects meta-analysis was used to pool risk ratios (RR) with 95% confidence intervals (CI) adjusted per mmol/L reduction in LDL-C. Fifty-three trials with 329,897 participants were included. Among participants, 39.5% were from Europe, 16.0% from North America, 9.0% from Japan, 2.8% from Australasia, 1.8% from South America, 1.1% from Asia, 0.6% from South Africa and 29.2% were unspecified. Among trials reporting ethnicities, there were 60.3% White, 20.2% Japanese, 9.4% Asian, 5.5% Black and 4.7% Latin American. There was reduction in MACE with LLT in regions including Australasia (RR 0.75, 95% CI 0.67-0.85), North America (RR 0.75, 95% CI 0.69-0.83), Europe (RR 0.78, 95% CI 0.71-0.86) and Japan (RR 0.73, 95% CI 0.63-0.85), and in Black ethnicity (RR 0.55, 95% CI 0.37-0.82). Head-to-head comparisons between regions and ethnicities revealed no significant differences in MACE reduction. Despite underrepresentation in clinical trials, regional and ethnic minority groups such as Australasia and Blacks appear to derive at least as much cardiovascular benefit from LLT.

Optimal low-density lipoprotein cholesterol target level in Korean acute myocardial infarction patients (

BackgroundCurrent treatment guidelines for acute myocardial infarction (AMI) recommend lowering low density lipoprotein cholesterol (LDL-C). However, previous clinical studies among East Asian AMI patients failed to prove its clinical efficacy of lipid lowering therapy based on Western target LDL-C level. Thus, the purpose of this study is directly to compare the clinical outcomes of target LDL-C < 70 mg/dL and < 55 mg/dL and identify optimal target LDL-C level and in Korean AMI patients. Methods and resultsA total of 2198 AMI patients in Korea AMI Registry – National Institute of Health were enrolled. Patients were initially divided into LDL-C non-target group (n = 1115) and target group (n = 1083). Successful achievement of follow up target LDL-C was defined as <70 mg/dL and ≥ 50% reduction from baseline. Target group patients were additionally divided to <70 mg/dL group (n = 698) and <55 mg/dL group (n = 385). Propensity score matching analysis was done in non-target vs. target group and <70 mg/dL vs. <55 mg/dL group. In the matched population, the risk of 3 years major adverse cardiac event (MACE) (13.0% vs 9.8%, HR: 0.73; 95% CI: 0.56–0.96; p = 0.025) was higher in non-target group patients. However, the risk of MACE was similar in <70 mg/dL and < 55 mg/dL group patients (10.0% vs 8.1%, HR: 0.75, 95% CI: 0.46–1.22; p = 0.247). ConclusionIn the present study, target LDL-C level of <70 mg/dL and ≥ 50% reduction from baseline level was associated with better clinical outcomes in Korean AMI patients. However, further lowering target LDL-C level of <55 mg/dL showed no additional benefits.

Sex disparities in lipid-lowering therapy and dyslipidemia control in a coronary rehabilitation program

Abstract Introduction Lipid control is one of the most important secondary cardiovascular prevention targets. Although cardiovascular disease is the most common cause of death for both genders, several studies have consistently shown that women are less likely to receive guideline-recommended secondary prevention medications after an acute coronary syndrome (ACS). Purpose To compare sex disparities in dyslipidemia control in a secondary prevention population with ACS in light of the ESC Dyslipidemia Guidelines. Methods We retrospectively analysed all patients who participated in a Coronary Rehabilitation Program (CRP) after an ACS from January 2011 to October 2019. Clinical data was collected at presentation and during 12 months follow-up. Doses of atorvastatin ≥40 mg, rosuvastatin ≥20 mg or a combination of a statin and ezetimibe were considered high-intensity LDL-lowering therapy (HIT). Results Of a total of 881 patients enrolled, mean age 55.0±10.0 year-old, 16.1% were female. At baseline there were no differences respecting clinical features between genders. At admission, 51.4% of patients had ST-elevation myocardial infarction and, concerning to cardiovascular risk factors, 63% patients had dyslipidemia, 46% had hypertension, 19% were diabetic, 76% were smokers or previous smokers, 27% had family history of coronary disease and 12% had previous coronary disease (ACS or &amp;gt;50% coronary artery stenosis). At hospital admission, females and males had similar mean LDL-levels [120.7 vs 118.1 mg/dL, t(708)=0.691, p=0.496]. The vast majority of patients from both genders were prescribed with statins on hospital discharge (99.5%) and maintain it during follow-up (99.3%). Female patients received more HIT during follow-up (67.8% vs 53.9% at baseline, p=0.015; 75.6% vs 59.0% after CRP, p=0.003; and 79.8% vs 65.1% at 1-year-follow-up, p=0.007). During follow-up, at the end of the CRP (about 3 months after event), male patients exhibit a better control of LDL [82.0 vs 75.6 mg/dL, t(597)=2.4, p=0.016)] with 12.8% vs 16.4% below 55 mg/dL and 29.8% vs 44.5% below 70 mg/dL (p=0.008). At 1-year follow-up, both genders exhibited similar LDL-control due to a worsening control of the male population (81.9 vs 80.6 mg/dL, t(540)=0.52, p=0.605). Only 13.3% of females had LDL below 55 mg/dL (vs 12.9%, p=0.921) and 32.5% below 70 mg/dL (vs 37.0%, p=0.432). Conclusion This real-life study showed that guideline recommended LDL target is not achieved in the majority of patients, even under a structured CRP. Unlike other reports, there were more women receiving potent anti-dyslipidemic therapy. Nevertheless, women showed a poor control of LDL-concentration after three months of ACS and a similar control after 1-year; this highlights the uncertainties concerning the efficacy of lipid-lowering therapy in women, an underrepresented population in clinical trials. Funding Acknowledgement Type of funding sources: None.

Efficacy of Lipid-Lowering Therapy during Cardiac Rehabilitation in Patients with Diabetes Mellitus and Coronary Heart Disease.

Background: Cardiac rehabilitation (CR) in patients with coronary heart disease (CHD) increases adherence to a healthy lifestyle and to secondary preventive medication. A notable example of such medication is lipid-lowering therapy (LLT). LLT during CR improves quality of life and prognosis, and thus is particularly relevant for patients with diabetes mellitus, which is a major risk factor for CHD. Design: A prospective, multicenter registry study with patients from six rehabilitation centers in Germany. Methods: During CR, 1100 patients with a minimum age of 18 years and CHD documented by coronary angiography were included in a LLT registry. Results: In 369 patients (33.9%), diabetes mellitus was diagnosed. Diabetic patients were older (65.5 ± 9.0 vs. 62.2 ± 10.9 years, p < 0.001) than nondiabetic patients and were more likely to be obese (BMI: 30.2 ± 5.2 kg/m2 vs. 27.8 ± 4.2 kg/m2, p < 0.001). Analysis indicated that diabetic patients were more likely to show LDL cholesterol levels below 55 mg/dL than patients without diabetes at the start of CR (Odds Ratio (OR) 1.9; 95% CI 1.3 to 2.9) until 3 months of follow-up (OR 1.9; 95% CI 1.2 to 2.9). During 12 months of follow-up, overall and LDL cholesterol levels decreased within the first 3 months and remained at the lower level thereafter (p < 0.001), irrespective of prevalent diabetes. At the end of the follow-up period, LDL cholesterol did not differ significantly between patients with or without diabetes mellitus (p = 0.413). Conclusion: Within 3 months after CR, total and LDL cholesterol were significantly reduced, irrespective of prevalent diabetes mellitus. In addition, CHD patients with diabetes responded faster to LTT than nondiabetic patients, suggesting that diabetic patients benefit more from LLT treatment during CR.

Abstract 13503: Relative Efficacy of Alirocumab, Bempedoic Acid, Evolocumab, Ezetimibe and Inclisiran Added to Statins for Reduction of Low Density Lipoprotein Cholesterol - A Network Meta-Analysis of Randomized Clinical Trials

Background: Many patients with hypercholesterolemia and/or cardiovascular disease are unable to achieve sufficient low-density lipoprotein cholesterol (LDL-C) reduction with statins alone (or are statin intolerant). This is increasingly the case with clinical guidelines recommending that lower LDL-C levels are beneficial for patients. This network meta-analysis (NMA) assessed the relative efficacy of lipid lowering therapies (LLTs) added to statins for reducing LDL-C. Methods: A systematic review of randomized controlled clinical trials to May 2020 identified 48 studies for inclusion in the primary NMA. The primary NMA included studies ≥12 weeks duration in which alirocumab, bempedoic acid, evolocumab, ezetimibe, or inclisiran were added to moderate-high intensity statins (or lower intensity / no statin in statin intolerant patients). Random effects NMA was used to analyse % change in LDL-C to compare the treatment effects indirectly. Results: Over 12 weeks, all non-statin LLTs significantly reduced LDL-C from baseline versus placebo. Evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were associated with largest LDL-C reductions, which were greater than those achieved with lower/alternative doses of alirocumab, bempedoic acid (± ezetimibe), ezetimibe and inclisiran (Table). Consistent results were observed in sensitivity analyses to address heterogeneity (excluding familial hypercholesterolemia and east Asian studies), in the subgroup NMA of studies in predominantly atherosclerotic cardiovascular disease patients, and in the statin intolerant subgroup NMA. Conclusions: All agents reduced LDL-C, however, the PCSK9 inhibitors evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were the most effective LLT regimens for reducing LDL-C when added to statins.

Adherence to statin therapy in patients with high and very high cardiovascular risk in real clinical practice

Despite the proven efficacy of lipid-lowering therapy, adherence to long-term statin therapy in patients with cardiovascular disease remains low.Aim. To study adherence to long-term statin therapy and factors associated with adherence in patients with high and very high cardiovascular risk (CVR) in real clinical practice.Materials and methods. The single-center cohort study included 53 patients (mean age 68.1 ± 10.2 years) with high or very high CVR on the SCORE scale and have been taking statins for at least 3 months prior to inclusion in the study. The level of low-density lipoprotein cholesterol (LDL-C), cognitive impairment (MoCA test), anxiety and depression (HADS scale), presence of senile asthenia (FRAIL scale), M. Charlson comorbidity index were assessed. Adherence to statin therapy was assessed using the original questionnaire. The correlation between patient adherence and ordinal variables for the scores of the studied scales was studied.Results. Completely adherent to statin therapy were only 12 (22%) patients, 14 (26%) were insufficiently adherent, 27 (51%) were non-adherent. The target level of LDL-С was achieved in 13 (25%) patients. 38 (72%) patients showed a decrease in cognitive functions; a positive correlation was found between adherence and the MoCA test (r = 0.44, p = 0.04). Clinical and subclinical depression and anxiety were noted in 12 (23%) and 14 (26%) patients, respectively. A statistically significant negative correlation was found between adherence and depression (r = –0.32; p = 0.04) and a positive correlation between adherence and anxiety (r = 0.44; p = 0.04). There was no statistically significant correlation between adherence and the FRAIL fragility scale, as well as the M. Charlson comorbidity index.Conclusions. Depression and cognitive decline are associated with decreased adherence to statin therapy.

Concepts and Controversies: Lipid Management in Patients with Chronic Kidney Disease.

Atherosclerotic cardiovascular disease (ASCVD) remains an important contributor of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is recognized as an important risk enhancer that identifies patients as candidates for more intensive low-density lipoprotein (LDL) cholesterol lowering. However, there is controversy regarding the efficacy of lipid-lowering therapy, especially in patients on dialysis. Among patients with CKD, not yet on dialysis, there is clinical trial evidence for the use of statins with or without ezetimibe to reduce ASCVD events. Newer cholesterol lowering agents have been introduced for the management of hyperlipidemia to reduce ASCVD, but these therapies have not been tested in the CKD population except in secondary analyses of patients with primarily CKD stage 3. This review summarizes the role of hyperlipidemia in ASCVD and treatment strategies for hyperlipidemia in the CKD population.

Интенсификация липидснижающей терапии у пациентов с тяжелыми нарушениями липидного обмена в условиях специализированных липидных центров. Возможности применения эволокумаба

The article presents current data on the prevalence of dyslipidemia worldwide and in the Russian Federation as the main cardiovascular risk factor of developing diseases associated with atherosclerosis. The article identifies the problems of low-level detection of dyslipidemia in the population and insufficient efficacy of lipid-lowering therapy to achieve the lipid profile target values depending on the established risk. It also presents the possibilities of modern lipid-lowering therapy with the use of innovative drugs — PCSK9 inhibitors and the use of evolocumab in accordance with evidence-based medicine. Adding that, the article shows the experience of two lipid control centers (in Kemerovo and Surgut) with the postulation of the need to expand the lipid control center chain to improve methods for providing medical care to patients with severe forms of dyslipidemia. The possibilities of intensifying lipid-lowering therapy in real clinical practice are outlined on the example of patients undergoing treatment in the lipid control center of Kemerovo. Evolocumab has been shown to be highly effective: reduction of atherogenic cholesterol fractions by 67% from the baseline and high safety of such therapy.KEYWORDS: lipid metabolism disorders, statins, lipid-lowering therapy, familial hypercholesterolemia, PCSK9 inhibitors, evolocumab.FOR CITATION: Barbarash O.L., Kashtalap V.V., Fedorova N.V. et al. Intensification of lipid-lowering therapy in patients with severe lipid metabolism disorders in specialized lipid control centers. Possibilities of using evolocumab. Russian Medical Inquiry. 2020;4(7):437–444. DOI: 10.32364/2587-6821-2020-4-7-437-444.

Efficacy of lipid-lowering therapy beyond statins to prevent cardiovascular events: a meta-analysis.

Efficacy of lipid-lowering therapy beyond statins to prevent cardiovascular events: a meta-analysis.

Long-term use of a combination of atorvastatin and ezetimibe in children with homozygous familial hypercholesterolemia

Background: Homozygous familial hypercholesterolemia (HoFH) is an underdiagnosed and undertreated genetic disorder of lipoprotein metabolism associated with mortality during young age due to accelerated atherosclerosis. There is limited data on the efficacy of lipid lowering therapies in HoFH. Methods: Medical records of 3 children with HoFH who received a combination of atorvastatin and ezetimibe for a mean duration of 11.6±1.5 years were retrospectively analysed. Results: There was a significant decrease in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) from the baseline levels (mean percent change in TC, LDL-C, TG and HDL-C of 58.5%, 56.2%, 67.5% and 29.7% respectively). Conclusions: We conclude that long-term use of a combination of atorvastatin and ezetimibe significantly lowers the plasma LDL-C concentrations in patients with HoFH without causing any significant adverse effects. Ours is the first study from India on long-term use of lipid modifying drug therapy in children with HoFH.

Lipid Lowering Therapy to Modify Plaque Microstructures.

Due to the pandemics of obesity and diabetes mellitus, especially in the Western countries, atherosclerotic cardiovascular disease (ASCVD) has become a major health burden and is expected to increase in the future. Modifying lipid targets, especially low-density lipoprotein cholesterol (LDL-C) level, has become the first-line therapy for primary and secondary prevention of ASCVD. Intravascular imaging modalities have contributed to elucidating clinical efficacy of lipid lowering therapy on atherosclerotic plaques. Optical coherence tomography (OCT) is a high-resolution imaging tool enables visualization of plaque microstructures associated with its instability. This modality has demonstrated favorable changes in plaque microstructures under lowering LDL-C level. In addition, clinical studies using OCT have suggested potential association of other lipid targets, including triglyceride and high-density lipoprotein cholesterol with plaque microstructures. Given continuing cardiovascular risks despite statin therapy, OCT will be an important imaging modality to evaluate novel therapeutic approaches that potentially modulates plaque instability.

虚血性心疾患患者に対する脂質低下療法の有用性について

虚血性心疾患患者に対する脂質低下療法の有用性について

Atorvastatin 10 mg plus ezetimibe versus titration to atorvastatin 40 mg: attainment of European and Canadian guideline lipid targets in high-risk subjects ≥65 years

BackgroundFew clinical studies have focused on the efficacy of lipid-lowering therapies in patients ≥65 years.MethodsAfter stabilization on atorvastatin 10 mg, hypercholesterolemic subjects ≥65 years at high/very high risk for CHD and not at LDL-C <1.81 mmol/L (with atherosclerotic vascular disease [AVD]) or <2.59 mmol/L (without AVD) were randomized to ezetimibe 10 mg plus atorvastatin 10 mg or uptitration to atorvastatin 20 mg (6 weeks) followed by uptitration to 40 mg (additional 6 weeks). A post-hoc analysis compared between-group differences in percent attainment of individual and combined LDL-C, non-HDL-C and Apo B targets based on recommendations from 2012 European and Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia treatment.ResultsAtorvastatin 10 mg plus ezetimibe produced significantly greater attainment of LDL-C, non-HDL-C, and Apo B individual and dual/triple targets vs. atorvastatin 20 mg for the entire cohort and very high-risk groups at 6 weeks. After 12 weeks, very high-risk subjects maintained significantly greater achievement of LDL-C <1.8 mmol/L (47% vs. 35%), non-HDL-C <2.6 mmol/L (63% vs. 53%) and Apo B <0.8 g/L (47% vs. 38%) single targets and dual/triple targets with atorvastatin 10 mg plus ezetimibe vs. atorvastatin 40 mg, while attainment of European target for high-risk subjects was generally similar for both treatments. Achievement of Canadian targets was significantly greater with combination therapy vs. atorvastatin 20 mg (6 weeks) or atorvastatin 40 mg (12 weeks).ConclusionsAtorvastatin 10 mg plus ezetimibe provided more effective treatment than uptitration to atorvastatin 20/40 mg for attainment of most European and Canadian guideline-recommended lipid targets in older at-risk patients.Trial registrationClinicalTrials.gov identifier NCT00418834.

Lipoprotein glomerulopathy may provide a key to unlock the puzzles of renal lipidosis

Lipoprotein glomerulopathy is an inherited renal disease characterized by unique lipoprotein thrombi in the glomerulus and is associated with the APOE mutation. Hu and colleagues investigated the genetic and clinical features of a large group of patients with lipoprotein glomerulopathy who carried APOE Kyoto, a major APOE variant. Their findings suggest its descent through a founder effect. Fibrate therapy in this group showed favorable results in the patient and renal survival rates.