Low-density Lipoprotein Cholesterol Goal Research Articles

Simulation study on LDL cholesterol target attainment, ASCVD events, and treatment cost of bempedoic acid in a representative German cohort of high- and very-high-CV risk patients

Abstract Background The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. For patients above goal despite statins and ezetimibe, additional LDL-C lowering can be achieved by treatment with bempedoic acid (BA) or PCSK9 inhibitors (PCSK9i). Purpose Simulation of LDL-C target attainment with BA as additional lipid-lowering medication in a representative cohort of German outpatients at high or very-high cardiovascular (CV) risk, calculation of the number of prevented atherosclerotic cardiovascular disease (ASCVD) events and budget impact. Methods Data were obtained from IQVIA™ Disease Analyzer database containing a representative sample of German outpatients. We selected patients with high or very-high CV risk (based on ESC/EAS guidelines), diagnosed hypercholesterolaemia and treatment with lipid-lowering medication. In patients with uncontrolled LDL-C, sequentially adding ezetimibe and BA was simulated using a Monte Carlo approach. Drug costs to control LDL-C by adding BA vs. PCSK9i were calculated based on current pricing in Germany. Considered were a scenario without BA and one with BA, in which BA was replaced by PCSK9i if LDL-C was still not controlled. The number of prevented events was calculated based on simulated LDL-C reduction. Results 105,577 patients met the inclusion criteria and entered the simulation model. 76,900 patients had very-high and 28,677 high CV risk. The baseline characteristics are depicted in Table 1. Only a minority of total patients (11.2%) achieved their risk-based LDL-C goal. Simulation of the sequential addition of ezetimibe to statins resulted in controlled LDL-C in 33.1% of total patients. Simulated addition of BA in patients with uncontrolled LDL-C despite statin and ezetimibe increased the percentage of controlled patients to 61.9% of total. The proportion of patients achieving LDL-C goals was higher in high- compared to very-high risk patients (Figure 1). Treatment with BA reduced the need for PCSK9i in patients on statin and ezetimibe from 66.6% to 37.8%. The considered scenario resulted in an anticipated reduction of drug costs by 35.9% per year on stable lipid-lowering medication. This effect was more pronounced in high-risk compared to very-high-risk patients (cost reductions of 40.6% and 34.4%, respectively). In this simulation model, the BA/PCSK9i strategy is projected to prevent 6,148 ASCVD events annually per 1 million patients on top of statin+ezetimibe, whereas LDL-C target achievement with PCSK9i alone would prevent 7,939 events. Conclusions A considerable larger proportion of high- and very-high-risk patients can achieve guideline-recommended LDL-C targets with escalated lipid-lowering medication. BA is projected to substantially decrease the need for PCSK9i treatment to achieve LDL-C targets which reduces drug costs compared to PCSK9i. LDL-C target attainment is projected to markedly reduce ASCVD events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Deutschland GmbH

Low-Density Lipoprotein Cholesterol Treatment Target Achievement in Patients with Myocardial Infarction, Percutaneous Coronary Intervention, or Stroke in Hong Kong.

Elevated concentrations of low-density lipoprotein cholesterol (LDL-C) are an important cause of recurrent cardiovascular events. This study aimed to describe the distribution and achieved concentrations of LDL-C among patients with myocardial infarction (MI), percutaneous coronary intervention (PCI), stroke, or transient ischaemic attack (TIA) in Hong Kong. Patients with a lipid test from a public hospital were identified from the Clinical Database and Analysis Reporting System of the Hong Kong Hospital Authority. Among patients with an inpatient hospitalization for MI, PCI, stroke or TIA, between 2003 to 2016, the distribution of LDL-C levels and the number (%) of patients achieving an absolute concentration of LDL-C 1.8 mmol/L at baseline (in-hospital) and during 12 months after hospital discharge were described. A total of 18417 patients were included (mean [SD] age, 70.0 [12.9] years; male, 60.3%), of which 3637 had MI, 4096 had PCI, and 10684 had stroke or TIA. At hospital discharge 12082 (65.6%) patients were prescribed statins, 690 (3.7%) were prescribed nonstatins, and 1849 (10.0%) achieved an LDL-C 1.8 mmol/L. Overall, 5654 (30.7%) patients did not have LDL-C result available within 12 months of discharge (MI, 605 [16.6%]; PCI, 432 [10.5%]; stroke or TIA, 4617 [43.2%]). Among the overall cohort, 4591 (24.9%) patients achieved an LDL-C 1.8 mmol/L during 12 months of follow-up (MI, 1288 [35.4%]; PCI, 1542 [37.6%]; stroke or TIA, 1761 [16.5%]). Improvements in achieved LDL-C were observed over time with a mean LDL-C 2.64 (0.92) mmol/L and 20.0% of patients achieving an LDL-C 1.8 mmol/L in 2003 as compared with a mean LDL-C 1.86 (0.70) mmol/L and 53.9% of patients achieving an LDL-C 1.8 mmol/L in 2016. In this single centre cohort study from Hong Kong, nearly half of patients with MI, PCI, or stroke in 2016 appear to qualify for intensification of lipid-modifying drug treatment in order to achieve a treatment goal of LDL-C 1.8 mmol/L. Further research is required in Hong Kong to assess contemporary management of LDL-C in a larger group of patients with established atherosclerotic cardiovascular disease.

Associations of lipid parameters with non-alcoholic fatty liver disease in type 2 diabetic patients according to obesity status and metabolic goal achievement.

AimsNon-obese non-alcoholic fatty liver disease (NAFLD) phenotype has sparked interest and frequently occurred in type 2 diabetes mellitus (T2DM). Information on associations between lipid parameters and NAFLD in non-obese patients with diabetes has been lacking. We aimed to investigate the relationships between lipid parameters and NAFLD according to obesity status and metabolic goal achievement in T2DM patients.MethodsA total of 1,913 T2DM patients who were hospitalized between June 2018 and May 2021 were cross-sectionally assessed. We used logistic regression models to estimate the associations of lipid parameters with NAFLD risk according to obesity and metabolic goal achievement status.ResultsHigher triglycerides, non-HDL-cholesterol, and all lipid ratios including (total cholesterol/HDL-cholesterol, triglyceride/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol, non-HDL-cholesterol/HDL-cholesterol), and lower HDL-cholesterol were associated with NAFLD risk in both non-obese and obese patients. The associations were stronger in non-obese patients than in obese patients. Further, the inverse associations of total cholesterol and LDL-cholesterol with NAFLD risk were only detected in non-obese patients. Triglycerides, HDL-cholesterol, and all lipid ratios studied were significantly associated with NAFLD risk, irrespective of whether the patients achieved their HbA1c, blood pressure, and LDL-cholesterol goal. The presence of poor lipids and lipid ratios were more strongly associated with NAFLD in patients who attained the HbA1c, blood pressure, and/or LDL-cholesterol goal than in those who did not achieve the goal attainment.ConclusionsThe associations of lipids and lipid ratios with NAFLD risk were stronger in T2DM patients who were non-obese and achieved the HbA1c, blood pressure, and/or LDL-cholesterol goal attainment.

Exploring the Efficacy of Alirocumab and Evolocumab in Reducing Low-Density Lipoprotein (LDL) Cholesterol Levels in Patients With Familial Hypercholesterolemia: A Systematic Review.

Patients with familial hypercholesterolemia (FH) have an increased risk of having abnormally high low-density lipoprotein cholesterol (LDL-C) levels. One of the main groups of drugs used for FH is statins. However, even with statins, most patients with FH do not achieve their pre-defined therapeutic LDL-C goals. Therefore, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) serve to decrease LDL-C levels in that population.A total of 838 articles were found after searching the databases of PubMed, MEDLINE, and Cochrane Library. After including only full-text peer-reviewed articles published in the last 10 years, 67 articles remained. Thirteen articles were put through the Cochrane bias assessment tool to screen for bias. After a strict quality assessment based on the criteria, eight articles were extracted and included in this systematic review.The data extraction from these studies showed that alirocumab and evolocumab were efficacious in decreasing LDL-C levels and achieving the pre-defined LDL-C goals. Many parameters influenced the strength of the LDL-C reduction: sample size of the population, genetic structure of the patients affected by FH, length of the trial, or baseline lipid-lowering therapy used. Therefore, one must consider several other factors while evaluating the percent reduction of PCSK9i. This review is limited because it did not comment on these drugs' cardiovascular outcomes or mortality benefits. In addition, some of the articles used in this systematic review have small sample sizes and short trial times, limiting the long-term evaluation of these drugs.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid.

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20-30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ≤30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

Low-density lipoprotein particles in atherosclerosis.

Among the diseases causing human death, cardiovascular disease (CVD) remains number one according to the World Health Organization report in 2021. It is known that atherosclerosis is the pathological basis of CVD. Low-density lipoprotein (LDL) plays a pivotal role in the initiation and progression of atherosclerotic CVD (ASCVD). LDL cholesterol (LDL-C) is the traditional biological marker of LDL. However, large numbers of patients who have achieved the recommended LDL-C goals still have ASCVD risk. In multiple prospective studies, LDL particle (LDL-P) is reported to be more accurate in predicting CVD risk than LDL-C. LDL-Ps differ in size, density and chemical composition. Numerous clinical studies have proved that the atherogenic mechanisms of LDL-Ps are determined not only by LDL number and size but also by LDL modifications. Of note, small dense LDL (sdLDL) particles possess stronger atherogenic ability compared with large and intermediate LDL subfractions. Besides, oxidized LDL (ox-LDL) is another risk factor in atherosclerosis. Among the traditional lipid-lowering drugs, statins induce dramatic reductions in LDL-C and LDL-P to a lesser extend. Recently, proprotein convertase subtilsin/kexin type 9 inhibitors (PCSK9i) have been demonstrated to be effective in lowering the levels of LDL-C, LDL-P, as well as CVD events. In this article, we will make a short review of LDL metabolism, discuss the discordance between LDL-C and LDL-P, outline the atherogenic mechanisms of action of LDL by focusing on sdLDL and ox-LDL, summarize the methods used for measurement of LDL subclasses, and conclude the advances in LDL-lowering therapies using statins and PCSK9i.

Physical activity to reduce PCSK9 levels.

The amount of physical activity (PA) people practice everyday has been reducing in the last decades. Sedentary subjects tend to have an impaired lipid plasma profile with a higher risk of atherosclerosis and related cardio- and cerebrovascular events. Regular PA helps in both primary and secondary cardiovascular prevention because of its beneficial effect on the whole metabolism. Several studies reported lower levels of plasma lipids in trained subjects, but the precise mechanisms by which PA modulates lipoproteins remain only partially described. Thereupon, proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serin protease whose main function is to reduce the amount of low-density lipoprotein cholesterol (LDL-C) receptors, with the direct consequence of reducing LDL-C uptake by the liver and increasing its circulating pool. Accordingly, recently developed PCSK9 inhibitors improved cardiovascular prevention and are increasingly used to reach LDL-C goals in patients at high CV risk. Whether PA can modulate the levels of PCSK9 remains partially explored. Recent studies suggest PA as a negative modulator of such a deleterious CV mediator. Yet the level of evidence is limited. The aim of this review is to summarize the recent reports concerning the regulatory role of PA on PCSK9 plasma levels, highlighting the beneficial role of regular exercise on the prevention of atherosclerosis and overall CV health.

Whats new in 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice?

2021 ESC Guidelines on cardiovascular disease prevention in clinical practice provides a comprehensive view on preventive cardiology. It presents strategies to reduce the burden of atherosclerotic cardiovascular disease (CVD), both at the individual level and at the population level. Healthy lifestyle and aggressive control of cardiovascular risk factors remain the cornerstone of prevention. Classification of individuals into risk groups based on their clinical characteristics followed by a stepwise treatment-intensification is a novel recommended approach. Updated risk charts - SCORE2 and SCORE2-OP - are intended for estimation of 10-year fatal and non-fatal CVD risk in apparently healthy individuals. Targets and goals for LDL cholesterol, blood pressure, and glycaemic control remain as recommended in recent ESC Guidelines.

Low-density lipoprotein cholesterol goal attainment in Germany: Results from the DA VINCI study

Background and aimsCardiovascular mortality is high in Germany. For patients with high or very high cardiovascular risk, the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT). This study aimed to assess dyslipidaemia management and achievement of the ESC/EAS guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals. MethodsThis European 18-country, cross-sectional, observational DA VINCI study (EUPAS22075) collected data during a single visit between June 2017 and November 2018 and included LLT in the preceding 12 months and the patients' most recent LDL-C measurement. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL-C goals while receiving stabilized LLT was assessed. Data from the German cohort are presented here. ResultsSeven German sites enrolled a total of 421 primary and secondary prevention patients, 327 were receiving stabilized LLT at the time of LDL-C measurement, i.e. statin monotherapy of high (16%; n = 53), moderate (49%; n = 160) or low (7%; n = 24) intensity, ezetimibe combination (18%; n = 58), proprotein convertase subtilisin/kexin type 9 antibody combination (3%; n = 9), and other LLT (7%; n = 23). The 2016 and 2019 risk-based LDL-C goals were attained by 46% (n = 149) and 28% (n = 92) of patients, respectively. ConclusionsThere is a large gap between ESC/EAS recommendations and LDL-C goal achievement in routine clinical practice in high and very high-risk patients in Germany. Low-to-moderate-intensity statin monotherapy was the most frequently used LLT; use of high-intensity statins and combination therapy was limited. In addition to optimizing statin intensity, combination with non-statin LLT may be needed in most of these patients.

Number of lipid-lowering medications and attainment of lipid goals in familial hypercholesterolemia patients: Data from the Latvian registry

Background and Aims : Attainment of low-density lipoprotein cholesterol (LDL-C) goals remains a challenge in patients with heterozygous familial hypercholesterolemia (FH). Combinations of lipid lowering medications (LLM) are commonly required. National registries play a crucial role to monitor quality of care in FH patients. We aimed to provide contemporary data on the number of used LLM, achieved lipid levels and attainment of LDL-C goals in FH patients from the Latvian Registry of FH (LRFH).

Prevalence and prognostic impact of lipid goal attainment and patient adherence to lowering lipid treatment: Data from community Italian setting

Background and Aims : The aim is to provide real-world data on low-density lipoprotein cholesterol (LDL-C) goal achievement at the time of current 2019 ESC/EAS Guidelines,treatment patterns and patient adherence to lowering lipid treatment (LLT).

One year follow-up of patients with familial hypercholesterolemia: Preliminary data from the HELLAS-FH registry

Background and Aims : To report follow-up findings in patients from the HELLAS-FH registry.Methods: We evaluated 139 adult patients with a clinical diagnosis of FH with a median follow-up of 12 months. Patient demographics, lipid profile, treatment and atherosclerotic cardiovascular disease (ASCVD) profile were recorded.Results: Patients were 53.2% male and aged 48.8±13.8 years. A proportion of 67.6% were receiving hypolipidemic treatment at enrollment and lipid profile was: total cholesterol (TCHOL) 215±60 mg/dL, low-density lipoprotein cholesterol (LDL-C) 141±55 mg/dL, high-density lipoprotein cholesterol (HDL-C) 49±13 mg/dL and triglycerides (TGs) 112 (77-156) mg/dL. Only 5.2% of on-treatment patients were on LDL-C target. After a median follow-up of 12 months (IQR 4-31 months), all patients were receiving hypolipidemic treatment. Specifically, 33.3% of patients started statin therapy, 22.7% had their statin therapy uptitrated, in 35.5% ezetimibe was added and in 14.2% a PCSK9i was prescribed. Follow-up lipid profile was: TCHOL 178±51 mg/dL, LDL-C 107±47 mg/dL, HDL-C 53±16 mg/dL and TGs 100 (70-136) mg/dL. At follow-up, 4.2% of patients were on target for LDL-C goal. Regarding ASCVD, 1 non-fatal myocardial infarction and 3 new diagnoses of peripheral arterial disease were recorded.Conclusions: After a median follow-up of 12 months, intensification of hypolipidemic therapy accompanied by an improvement of lipid profile was observed. Despite that, achievement of LDL-C target remained poor. A new ASCVD event was recorded in 2.8% of patients. Background and Aims : To report follow-up findings in patients from the HELLAS-FH registry. Methods: We evaluated 139 adult patients with a clinical diagnosis of FH with a median follow-up of 12 months. Patient demographics, lipid profile, treatment and atherosclerotic cardiovascular disease (ASCVD) profile were recorded. Results: Patients were 53.2% male and aged 48.8±13.8 years. A proportion of 67.6% were receiving hypolipidemic treatment at enrollment and lipid profile was: total cholesterol (TCHOL) 215±60 mg/dL, low-density lipoprotein cholesterol (LDL-C) 141±55 mg/dL, high-density lipoprotein cholesterol (HDL-C) 49±13 mg/dL and triglycerides (TGs) 112 (77-156) mg/dL. Only 5.2% of on-treatment patients were on LDL-C target. After a median follow-up of 12 months (IQR 4-31 months), all patients were receiving hypolipidemic treatment. Specifically, 33.3% of patients started statin therapy, 22.7% had their statin therapy uptitrated, in 35.5% ezetimibe was added and in 14.2% a PCSK9i was prescribed. Follow-up lipid profile was: TCHOL 178±51 mg/dL, LDL-C 107±47 mg/dL, HDL-C 53±16 mg/dL and TGs 100 (70-136) mg/dL. At follow-up, 4.2% of patients were on target for LDL-C goal. Regarding ASCVD, 1 non-fatal myocardial infarction and 3 new diagnoses of peripheral arterial disease were recorded. Conclusions: After a median follow-up of 12 months, intensification of hypolipidemic therapy accompanied by an improvement of lipid profile was observed. Despite that, achievement of LDL-C target remained poor. A new ASCVD event was recorded in 2.8% of patients.

A behavioural science research programme to understand the barriers to achieving recommended LDL cholesterol goals

Background and Aims : Evidence suggests a gap between clinical guideline development and successful real-world implementation, with an estimated 4 out of 10 patients receiving non-evidenced-based care.1 Ensuring research addresses the drivers of this evidence implementation gap is a key health priority. Involving clinicians and patients in research design can help to synthesise existing knowledge and generate key recommendations to guide research. We convened an expert panel, as first step to help guide a 2-year behavioural science research programme - Cardio Connect: which aims to explore barriers to achieving recommended LDL cholesterol goals.Methods: An expert panel of N=4 behavioural scientists, N=5 clinicians (cardiologists and lipidologists) and a patient organisation representative, from Germany, Italy, and UK, attended a 3-hour virtual meeting. Behavioural scientists proposed a mixed-methods research programme and invited discussion.Results: Key research guiding principles emerged from the experts discussion and experience: 1) explore experiences of treatment access inequality, accounting for regional differences; 2) explore ways to better empower patients; 3) understand differences in the application of clinical guidelines between clinical specialties; 4) explore perceptual factors (e.g. clinicians concerns) and practical barriers (e.g. financial restraints) to delivering evidence-based care from patients’ and clinicians’ perspectives. Experts also advised on ways to engage the clinical and patient community: 1) disseminate findings at local and disease specific conferences; 2) engage patient organisations to reach under-served patients.Conclusions: Research is needed to better understand the evidence-implementation gap in dyslipidaemia. This research programme will apply behavioural science and be co-designed with patient and clinical communities. Background and Aims : Evidence suggests a gap between clinical guideline development and successful real-world implementation, with an estimated 4 out of 10 patients receiving non-evidenced-based care.1 Ensuring research addresses the drivers of this evidence implementation gap is a key health priority. Involving clinicians and patients in research design can help to synthesise existing knowledge and generate key recommendations to guide research. We convened an expert panel, as first step to help guide a 2-year behavioural science research programme - Cardio Connect: which aims to explore barriers to achieving recommended LDL cholesterol goals. Methods: An expert panel of N=4 behavioural scientists, N=5 clinicians (cardiologists and lipidologists) and a patient organisation representative, from Germany, Italy, and UK, attended a 3-hour virtual meeting. Behavioural scientists proposed a mixed-methods research programme and invited discussion. Results: Key research guiding principles emerged from the experts discussion and experience: 1) explore experiences of treatment access inequality, accounting for regional differences; 2) explore ways to better empower patients; 3) understand differences in the application of clinical guidelines between clinical specialties; 4) explore perceptual factors (e.g. clinicians concerns) and practical barriers (e.g. financial restraints) to delivering evidence-based care from patients’ and clinicians’ perspectives. Experts also advised on ways to engage the clinical and patient community: 1) disseminate findings at local and disease specific conferences; 2) engage patient organisations to reach under-served patients. Conclusions: Research is needed to better understand the evidence-implementation gap in dyslipidaemia. This research programme will apply behavioural science and be co-designed with patient and clinical communities.

LDL-cholesterol goal attainment through optimal implementation of the 2019 ESC/EAS dyslipidemia treatment algorithm in European patients with/without atherosclerotic cardiovascular disease: Simulation study from DA VINCI

Background and Aims : In the European-wide DA VINCI study, only 33% of patients attained their risk-based 2019 ESC/EAS guideline LDL-C goals. We aimed to simulate the impact of the step-wise implementation of the ESC/EAS lipid-lowering treatment (LLT) pathway on LDL-C goal attainment across risk categories.

What should be the goal of cholesterol-lowering treatment? A quantitative evaluation dispelling guideline myths.

Guidelines for cholesterol-lowering treatment generally include extensive review of epidemiological and clinical trial evidence. However, the next logical step, the translation of evidence into clinical advice, occurs not entirely by reasoning, but by a form of consensus in which the prejudices and established beliefs of the societies with interests in cardiovascular disease convened to interpret the evidence are prominent. Methods, which are the subject of this review, have, however, been developed by which clinical trial evidence can be translated objectively into best practice. Guidelines differ in their recommended goals for cholesterol-lowering treatment in the prevention of atherosclerotic cardiovascular disease (ASCVD). Proposed goals are LDL-cholesterol 2.6 mmol/l (100 mg/dl) or less in lower risk, LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less in higher risk, non-HDL-cholesterol decrease of at least 40% or LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less or decreased by at least 50% whichever is lower. Evidence from clinical trials of statins, ezetimibe and proprotein convertase subtilisin/kexin type 9-inhibitors can be expressed in simple mathematical terms to compare the efficacy on ASCVD incidence of clinical guidance for the use of cholesterol-lowering medication. The target LDL-cholesterol of 2.6 mmol/l (100 mg/dl) is ineffective and lacks credibility. Cholesterol-lowering medication is most effective in high-risk people with raised LDL-cholesterol. The best overall therapeutic target is LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less or decreased by at least 50% whichever is lower. The use of non-HDL-cholesterol as a therapeutic goal is less efficacious. Aiming for LDL-cholesterol 1.4 mmol/l (55 mg/dl) or less as opposed to 1.8 mmol/l produces only a small additional benefit. Evidence for apolipoprotein B targets in hypertriglyceridaemia and in very high ASCVD risk should be more prominent in future guidelines. The LDL-cholesterol goal of 2.6 mmol/l or less should be abandoned. Percentage decreases in LDL-cholesterol or non-HDL-cholesterol concentration are better in people with initial concentrations of less than 3.6 mmol/l. The LDL-cholesterol target of 1.8 mmol/l is most effective when initial LDL-cholesterol is more than 3.6 mmol/l in both primary and secondary prevention.

Intensity of lipid-lowering therapy, adherence and LDL-cholesterol goal attainment in patients with coronary heart disease

Background and Aims : To examine patterns of lipid-lowering therapy (LLT) use, and persistence and adherence among coronary heart disease (CHD) patients and their association with lipoprotein cholesterol (LDL-C) goal attainment.

The prevalence of hyperlipidemia and features of lipid-lowering therapy in patients with myocardial infarction according to the Russian register of acute myocardial infarction REGION-MI

Aim To study the prevalence of hyperlipidemia in patients with myocardial infarction (MI) in the Russian Federation; to assess the compliance with clinical practice guidelines of the lipid-lowering therapy prescribed upon discharge from the hospital; and to determine the number of patients who are indicated for the combination lipid-lowering therapy to achieve the low-density lipoprotein cholesterol (LDL-C) goal.Material and methods REGION-MI is Russian rEGIstry Of acute myocardial iNfarction, a multicenter, retrospective and prospective observational study. The observation period was divided into 3 stages: observation during the stay in the hospital and at 6 and 12 months after the inclusion in the registry. Plasma total cholesterol (TC) and LDL-C were measured in all patients on admission. Evaluation of the prescribed lipid-lowering therapy included the intensity of the treatment.Results The study included 3 620 patients; 62.4 of them had hyperlipidemia on admission. Mean TC on admission was 5.29 mmol/l and LDl-C level was 3.35 mmol/l. Upon discharge, 95.4% of patients after myocardial infarction continued on or were prescribed statin therapy; ezetimibe was prescribed to 1.22% of patients. Patients with an extremely high level of LDL-C >5 mmol/l accounted for 10.7% of patients with hyperlipidemia. The target level of LDL-C ≤1.4 mmol/l cannot be achieved with the statin and ezetimibe combination therapy in these patients; drugs from the group of PCSK9 inhibitors are indicated for them.Conclusion According to the data of the Russian registry of acute myocardial infarction, REGION-MI, a high incidence of hyperlipidemia is observed in patients with acute MI. Despite multiple studies that have proven the importance of achieving a low LDL-C level and good tolerance and safety of ezetimibe and PCSK9 inhibitors, the prescription frequency of combination therapy remains unreasonably low. Results of a simulation study that was conducted in Sweden and the data of the REGION-MI registry showed that PCSK9 inhibitors as a part of the combination therapy are indicated for many patients. The combination therapy is presently the most powerful type of lipid-lowering treatment that allows, in most cases, achievement of the LDL-C goal.

Impact of a Population Genomic Screening Program on Health Behaviors Related to Familial Hypercholesterolemia Risk Reduction.

Background:Limited information is available regarding clinician and participant behaviors after disclosure of genomic risk variants for familial hypercholesterolemia (FH) from a population genomic screening program.Methods:We conducted a retrospective cohort study of MyCode participants with an FH risk variant beginning 2 years before disclosure until January 16, 2019. We analyzed lipid-lowering prescriptions (clinician behavior), medication adherence (participant behavior), and LDL (low-density lipoprotein) cholesterol levels (health outcome impact) pre- and post-disclosure. Data were collected from electronic health records and claims.Results:The cohort included 96 participants of mean age 57 (22–90) years with median follow-up of 14 (range, 3–39) months. Most (90%) had a hypercholesterolemia diagnosis but no specific FH diagnosis before disclosure; 29% had an FH diagnosis post-disclosure. After disclosure, clinicians made 36 prescription changes in 38% of participants, mostly in participants who did not achieve LDL cholesterol goals pre-disclosure (81%). However, clinicians wrote prescriptions for fewer participants post-disclosure (71/96, 74.0%) compared with pre-disclosure (81/96, 84.4%); side effects were documented for most discontinued prescriptions (23/25, 92%). Among the 16 participants with claims data, medication adherence improved (proportion of days covered pre-disclosure of 70% [SD, 24.7%] to post-disclosure of 79.1% [SD, 27.3%]; P=0.05). Among the 52 (54%) participants with LDL cholesterol values both before and after disclosure, average LDL cholesterol decreased from 147 to 132 mg/dL (P=0.003).Conclusions:Despite disclosure of an FH risk variant, nonprescribing and nonadherence to lipid-lowering therapy remained high. However, when clinicians intensified medication regimens and participants adhered to medications, lipid levels decreased.

Intensity of and Adherence to Lipid-Lowering Therapy as Predictors of Major Adverse Cardiovascular Outcomes in Patients With Coronary Heart Disease.

Background The effectiveness of lipid-lowering therapy (LLT) is affected by both intensity and adherence. This study evaluated the associations of LLT intensity, adherence, and the combination of these 2 aspects of LLT management with the risk of major adverse cardiovascular events (MACE) in people with coronary heart disease. Methods and Results This is an observational study of all adults who suffered a myocardial infarction or had coronary revascularization during 2012 to 2018 and initiated LLT in Stockholm, Sweden. Study exposures were LLT adherence (proportion of days covered), LLT intensity (expected reduction of low-density lipoprotein cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity during the previous 12 months were calculated. The primary outcomes were MACE (nonfatal myocardial infarction or stroke and death); secondary outcomes were low-density lipoprotein cholesterol goal attainment and individual components of MACE. We studied 20 490 patients aged 68±11 years, 75% men, mean follow-up 2.6±1.1 years. Every 10% increase in 1-year adherence, intensity, or adherence-adjusted intensity was associated with a lower risk of MACE (hazard ratio [HR], 0.94 [95% CI, 0.93-0.96]; HR, 0.92 [95% CI, 0.88-0.96]; and HR, 0.91 [95% CI, 0.89-0.94], respectively) and higher odds of attaining low-density lipoprotein cholesterol goals (odds ratio [OR],1.12 [95% CI, 1.10-1.15]; OR, 1.42 [95% CI, 1.34-1.51], and OR, 1.16 [95% CI, 1.19-1.24], respectively). Among patients with good adherence (≥80%), the risk of MACE was similar with low-moderate and high-intensity LLT despite differences in the low-density lipoprotein cholesterol goal attainment with the treatment intensities. Discontinuation ≥1 year increased the risk markedly (HR,1.66 [95% CI, 1.23-2.22]). Conclusions In routine care, good adherence to LLT was associated with the greatest benefit for patients with coronary heart disease. Strategies that improve adherence and use of intensive therapies could substantially reduce cardiovascular risk.

The DA VINCI study: is Ireland achieving ESC/EAS guideline–directed LDL-C goals?

BackgroundThe EU-wide, cross-sectional observational study of lipid-lowering therapy (LLT) use in secondary and primary care (DA VINCI) assessed the proportion of patients achieving low-density lipoprotein cholesterol (LDL-C) goals recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines and provided an insight into regional use of LLT in Europe, including Ireland.AimsThis analysis focuses on data from patients in Ireland who participated in the DA VINCI study.MethodsThe DA VINCI study enrolled patients receiving LLT at primary and secondary care sites across 18 European countries between June 2017 and November 2018. The study assessed the achievement of risk-based 2016 and 2019 ESC/EAS LDL-C goals. This subgroup analysis aimed to evaluate LDL-C goal attainment in an Irish cohort of primary and secondary care patients.ResultsIn total, 198 patients from Ireland were enrolled from three primary care and three secondary care centres. Most patients were White and male, and were receiving moderate- or high-intensity statin therapy (most frequently atorvastatin or rosuvastatin). Few patients (< 10%) were receiving combination therapy of statin and ezetimibe. Approximately 60% of patients achieved their 2016 ESC/EAC LDL-C goals while less than half the patients achieved their 2019 ESC/EAS goals. Approximately half of secondary prevention patients achieved their 2016 ESC/EAS goals and only 20% of secondary prevention patients achieved their 2019 ESC/EAS goals.ConclusionsThese results highlight the disparity between dyslipidaemia management in clinical practice in Ireland and guideline recommendations.Trial registrationENCePP; EU PAS 22,075; date registered 06 February 2018.