Target Low-density Lipoprotein Cholesterol Levels Research Articles

The Impact of the 2019 European Guideline for Cardiovascular Risk Management: A Cross-Sectional Study in General Practice.

The aim of this study was to assess the impact of the 2019 published European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline on cardiovascular (CV) risk management compared with its predecessor from 2016 in a cohort in general practice. We performed a cross-sectional retrospective study with data from electronic medical records. The study cohort included 103,351 patients with known CV risk. We assessed changes in CV risk classification and low-density lipoprotein cholesterol (LDL-C) target values, the impact on LDL-C achievement rates, and the current lipid-lowering treatments. Under the 2019 ESC guideline, CV risk categories changed in 27.5% of patients, LDL-C target levels decreased in 71.4% of patients, and LDL-C target achievement rate dropped from 31.1% to 16.5%. Among non-achievers according to the 2019 guideline, 52.2% lacked lipid-lowering drugs entirely, and 41.5% had conventional drugs at a submaximal intensity. Of patients in the high-risk and very high-risk categories, at least 5% failed to achieve the LDL-C target level despite treatment at maximal intensity with conventional lipid-lowering drugs, making them eligible for PCSK-9 inhibitors. In conclusion, the 2019 ESC/EAS guideline lowered LDL-C target values for the majority of patients in general practice and halved LDL-C target achievement rates. There is still a large undeveloped potential to lower CV risk by introducing conventional lipid-lowering drugs, particularly in patients at high or very high CV risk. A substantial proportion of the patients can only achieve their LDL-C targets using PCSK-9 inhibitors, which would currently require an at least 10-fold increase in prescribing of these drugs.

Achievement of LDL-C Targets Defined by ESC/EAS (2011) Guidelines in Risk-Stratified Korean Patients with Dyslipidemia Receiving Lipid-Modifying Treatments.

BackgroundThis study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs).MethodsIn this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed.ResultsGuideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators’ assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients’ LDL-C levels was the primary reason for non-intensification of statin therapy.ConclusionAchievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.

Current lipid lowering treatment and attainment of LDL targets recommended by ESC/EAS guidelines in very high-risk patients with established atherosclerotic cardiovascular disease: Insights from the START registry

BackgroundCurrent European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias have further reduced low density lipoprotein-cholesterol (LDL-C) targets, as compared to the guidelines released in 2016. These targets are particularly restraining for patients at very high risk (VHR). MethodsUsing the data from a nationwide, prospective registry on patients with established atherosclerotic cardiovascular disease (ASCVD), we sought to assess: 1) the contemporary use of conventional cholesterol-lowering therapies and the achievement of LDL-C goals according to previous and current ESC guidelines in subjects at VHR; 2) the proportion of VHR patients potentially eligible for proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) treatment. ResultsAmong the 5053 patients with data available, 4751 (94.0%) were deemed as VHR. Among these patients, the mean LDL-C levels were 62.4 ± 47.7 mg/dl at enrollment. A high dose of statin was used in 54.9%, while the association of high dose statin and ezetimibe was prescribed in 4.8% of VHR patients. A target level of LDL-C < 70 mg/dl recommended by 2016 ESC guidelines was reached by 58.1%, while a target of <55 mg/dl and LDL-C reduction ≥50% recommended by 2019 ESC guidelines, would be reached by 3.2% of patients at VHR. Accordingly, 9.4% and 1.4% of VHR patients would be eligible for PCSK9i according to ESC guidelines and Italian regulations, respectively. ConclusionsIn VHR patients enrolled in this large cohort of established ASCVD managed by cardiologists, the lipid management and LDL-C targets attainment is largely suboptimal.

Naturally Occurring PCSK9 Inhibitors.

Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.

Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels.

Background: atherosclerotic process inexorably advances in patients reaching low-density lipoprotein cholesterol (LDL-C) targets. An attractive hypothesis is that lipoprotein particles (very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL)), could contribute to residual risk. The present study aims to investigate the relationship between carotid intima-media thickness (IMT) and different lipoprotein subfractions in a cohort of healthy postmenopausal women. Methods: 75 postmenopausal women, at LDL-C target levels without overt cardiovascular disease, underwent biochemical analyses (including subfraction assay of plasma lipoproteins) and carotid ultrasound examination. Results: a statistically significant correlation between VLDL and carotid IMT (p < 0.001) was found. No significant correlation was found between carotid IMT and LDL-C (p = 0.179), IDL-C (p = 0.815), high-density lipoprotein (HDL) (p = 0.855), and LDL score (p = 0.240). Moreover, IMT is significantly correlated to LDL particle diameter (p = 0.044). After adjusting for age, systolic blood pressure, body mass index, smoking habits, glucose plasma concentration, and Lipoprotein(a) (Lpa) levels, multivariate analysis showed that women in the third tertile of VLDL-C, compared with those in the first tertile, were significantly associated to the highest IMT (p = 0.04). Conclusions: in this cohort of postmenopausal women, VLDL-C was significantly associated to carotid IMT, independent of main cardiovascular risk factors. These findings pave the way for targeting circulating concentrations of VLDL-C to reduce cardiovascular events in patients with target LDL-C levels.

Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study.

European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients. We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge. Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/l (2016 target) and (23%) <1.4 mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6 mmol/l (2016) and 37% <2.2 mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0 mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were ≥2.3 mmol/l and 41% ≥1.5 mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target. There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.

The Role of Red Yeast Rice Based Preparations for Non-Pharmacological Correction of Dyslipidemia in Patients with Low and Moderate Cardiovascular Risk (Expert Opinion)

The Russian Federation is among countries with high cardiovascular risk. Hypercholesterolemia is a leading risk factor for the development of atherosclerotic cardiovascular diseases. To achieve low-density lipoprotein cholesterol (LDL-C) targets, such approaches as lifestyle changes and pharmacological correction, based on the use of statins, are applied. At the same time, a significant proportion of the population has moderate hypercholesterolemia and is characterized by low or moderate cardiovascular risk. Although first-line recommendations should be followed, a healthy lifestyle alone is not enough to achieve target levels of LDL-C, which means that even people with low to moderate risk may end up with the prospect of lifelong therapy with lipid-lowering drugs. These individuals do not have an indication for lipid-lowering therapy, and they are usually recommended a change in diet and supplementation. Innovative nutritional strategies have been developed to manage dyslipidemia. They were based either on changing some “risky” food components or on encouraging the consumption of “healthy” functional foods and/or nutraceuticals. Nutraceuticals (registered as food supplements in Russia) is an innovative way to help control LDL-C at low and moderate risk individuals without lipid-lowering drugs and as nutritive support for the cholesterol-lowering diet. Red yeast rice (RYR) based preparations have been already developed and available at the moment. RYR based preparations can be considered in patients with low and moderate cardiovascular risk, who have not reached the target level of LDL-C and have no indications for statin therapy or have statin intolerance. RYR based preparations contains a statin-like substance monacolin K in a dose of 3 mg. In randomized clinical trials, it was proved that the use of high-quality RYR nutraceutical leads to a decrease in LDL-C by an average of 20% without increasing the risk of side effects like for statins. Evaluation of dietary supplements and functional foods should necessarily include not only evidence of beneficial effects with respect to effects on the lipid profile and atherosclerosis, but also proven good tolerability. The manufacturing standard for these products is also important, guaranteeing component standardization and quality. RYR analogues should guarantee the absence of mycotoxin in their composition. In Russia, programs are needed for the primary prevention of atherosclerotic cardiovascular diseases with effects on hypercholesterolemia at the population level.

Cost-effectiveness of statin therapy for secondary prevention among patients with coronary artery disease and baseline LDL-C 70–100 mg/dL in Taiwan

The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70-100mg/dL in Taiwan could be cost-effective. A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. Moderate-intensity statin use, a treatment regimen expected to achieve LDL <70mg/dL in the base case, resulted in a net gain of 562 QALYs but with an additional expenditure of $11.4 million per 10,000 patients over ten years. The ICER was $20,288 per QALY gained. The probabilities of being cost-effective at willingness-to-pay thresholds of one and three gross domestic product per capita ($24,329 in 2017) per QALY were 51.1% and 94.2%, respectively. Annual drug cost was the most influential factor on the ICER. Lowering the target LDL-C level from 100 to 70mg/dL among treatment-naïve CAD patients could be cost-effective given the health benefits of preventing cardiovascular events and deaths.

Lipid Lowering Treatment and Eligibility for PCSK9 Inhibition in Post-Myocardial Infarction Patients in Italy: Insights from Two Contemporary Nationwide Registries.

Introduction The current use of lipid lowering therapies and the eligibility for proprotein convertase subtilisin/kexin-9 (PCSK9) inhibitors of patients surviving a myocardial infarction (MI) is poorly known. Methods Using the data from two contemporary, nationwide, prospective, real-world registries of patients with stable coronary artery disease, we sought to describe the lipid lowering therapies prescribed by cardiologists in patients with a prior MI and the resulting eligibility for PCSK9 inhibitors according to the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) and the Italian regulatory agency (Agenzia Italiana del Farmaco; AIFA) criteria. The study cohort was stratified according to the following low-density lipoprotein cholesterol (LDL-C) levels at the time of enrolment: <70 mg/dl; 70–99 mg/dl and ≥100 mg/dl. Results Among the 3074 post-MI patients with LDL-C levels available, a target level of LDL-C < 70 mg/dl was present in 1186 (38.6%), while 1150 (37.4%) had LDL-C levels ranging from 70 to 99 mg/dl and the remaining 738 (24.0%) an LDL-C ≥ 100 mg/dl. A statin was prescribed more frequently in post-MI patients with LDL-C levels <70 mg/dl (97.1%) compared to the other LDL-C groups (p < 0.0001). A low dose of statin was prescribed in 9.3%, while a high dose in 61.4% of patients. Statin plus ezetimibe association therapy was used in less than 18% of cases. In the overall cohort, 293 (9.8%) and 450 (22.2%) resulted eligible for PCSK9 inhibitors, according to ESC/EAS and AIFA criteria, respectively. Conclusions Post-MI patients are undertreated with conventional lipid lowering therapies. A minority of post-MI patients would be eligible to PCSK9 inhibitors according to ESC/EAS guidelines and Italian regulatory agency criteria.

A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke

BackgroundThe use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied.MethodsIn this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes.ResultsA total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P=0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups.ConclusionsAfter an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.)

Low-Density Lipoprotein Cholesterol Targets in Patients With Coronary Heart Disease in Extremadura (Spain): LYNX Registry.

BackgroundLow-density lipoprotein cholesterol (LDL-C) contributes decisively to the development of cardiovascular disease (CVD). In the LYNX registry we determined the rate of achievement of the target value of LDL-C, the use of lipid-lowering therapy (LLT) and the predictive factors of not reaching the target in patients with stable coronary heart disease (CHD).MethodsLYNX included consecutive patients with stable CHD treated at the University Hospital of Caceres, Extremadura (Spain) from September 2016 to September 2018, and those who must have an LDL-C target below 70 mg/dL according to the European Society of Cardiology (ESC) 2016 guidelines. The variables independently associated with the breach of the LDL-C objective were evaluated by multivariable logistic regression.ResultsA total of 674 patients with stable CHD were included. The average LDL-C levels were 68.3 ± 24.5 mg/dL, with 56.7% showing a level below 70 mg/dL. LLT was used by 96.7% of patients, 71.7% were treated with high-powered statins and 30.1% with ezetimibe. The risk of not reaching the target value of LDL-C was higher in women, in active smokers, and in those who had multivessel CHD or had atrial fibrillation. Patients with diabetes mellitus, those who took potent statins or co-administration treatment with ezetimibe were more likely to reach the target level of LDL-C.ConclusionsThe treatment of dyslipidemia in patients with chronic CHD remains suboptimal; however, an increasing number of very high-risk patients achieve the LDL-C objective, although there is still enormous potential to improve cardiovascular outcome through the use of more intensive LLT.

Statin Therapy and Low-Density Lipoprotein Cholesterol Reduction after Acute Coronary Syndrome: Insights from the United Arab Emirates.

Background and Aims:Attaining guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals (<70 mg/dl or ≥ 50% reduction) with statin therapy remains suboptimal after an acute coronary syndrome (ACS). This study aimed to assess the level of lipid-lowering therapy (LLT) utilization and achievement of LDL-C targets after ACS hospitalization in the United Arab Emirates (UAE).Methods:A retrospective, observational, longitudinal database analysis of Emirati patients with ACS or stable coronary heart disease was evaluated from January 2015 to June 2018. Patients were divided based on whether or not they were treated with LLT at index hospitalization with ACS. LDL-C target level achievement was assessed according to the 2013 American College of Cardiology/American Heart Association and European Society of Cardiology/European Atherosclerosis Society guidelines.Results:A total of 3,066 patients (mean age 65.5 ± 14 years) met the inclusion criteria. Overall, 58.1% (n = 1782) of the patients in the cohort were on LLT during the ACS hospitalization. At discharge, the mean LDL-C level was 84.8 ± 39.0 mg/dl, and 28%, 21%, and 9% received high-, moderate-, and low-intensity statins, respectively. At 6 months (n = 2046; 66.7%), 27.7% and 16.7% achieved an LDL-C of <70 mg/dl and 70–100 mg/dl, respectively. The highest level of LDL-C reduction by 50% within 6 months was observed among patients using moderate-intensity statin (37.2%).Conclusion:A large proportion of Emirati patients were not on LLT after ACS, and the rate of LDL-C target value attainment was extremely poor (27.7%). Optimal statin utilization by closely implementing the guidelines in the UAE is recommended.

PCSK9 Inhibition and Atherosclerosis: Current Therapeutic Option and Prospection.

Low-density lipoprotein cholesterol (LDL-C) is a pivotal factor in atherosclerotic cardiovascular disease (ASCVD), the leading cause of worldwide mortality. The limitations of statin therapy require alternative treatment strategies to achieve target LDL-C level. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in LDLR recycling, consequently regulating plasma cholesterol levels. Monoclonal antibodies targeting PCSK9 increased expression of LDLRs at the cell surface and therefore decreased circulating LDL-C. PCSK9 inhibitors have shown great efficacy in reducing plasma LDL-C levels, which needs to inject once or twice monthly. Though SPIRE sponsors concern the immunogenicity and terminate trials early, FOURIER and ODYSSER OUTCOME trials improved the efficacy of PCSK9 inhibitors in LDL-C reduction. Inclisiran actually is a small interfering RNA (siRNA) developed to inhibit PCSK9 messenger RNA, leading to reduced concentrations of the PCSK9 protein and thereby lower concentrations of LDL-C. Inclisiran is a latest alternative treatment to cholesterol-lowering therapeutics. Twice injections of inclisiran durably reduced LDL-C levels over 1year. siRNA therapeutics provided a simple, novel, and less frequent approach to LDL-C reduction in phase I and II trials, which may be used either as in combination with statin therapeutics or a stand-alone therapy in the future.

An expert opinion paper on statin adherence and implementation of new lipid-lowering medications by the ESC Working Group on Cardiovascular Pharmacotherapy: Barriers to be overcome

Benefits and safety on statins have been well-established over 20 years of research. Despite this, the vast majority of patients are not adequately treated and do not achieve the low-density lipoprotein cholesterol target levels. This is mainly due to poor adherence, which is associated with dangerous and sometimes fatal outcomes. To increase adherence and prevent worse outcomes, a combination therapy with lower dosage of statins and new lipid-lowering drugs may be used. However, the implementation of new lipid-lowering drugs in European countries is still at the beginning. For these reasons, the aim of this position paper is to give an up-to-date indication from the ESC Working Group on Cardiovascular Pharmacotherapy in order to discuss the barriers towards statins adherence and new lipid-lowering drugs implementation in Europe.

Efficacy and Safety of High-Dose Atorvastatin in Moderate-to-High Cardiovascular Risk Postmenopausal Korean Women with Dyslipidemia.

ObjectivePostmenopausal women show a more atherogenic lipid profile and elevated cardiovascular risk compared to premenopausal women. The aim of this study was to investigate the efficacy and safety of high-dose atorvastatin on the improvement of the blood lipid profile of postmenopausal women in Korea.MethodsThis study is a prospective, open-label, single-arm clinical trial that was conducted in 3 teaching hospitals. Postmenopausal women with a moderate-to-high cardiovascular risk, according to guidelines from the Korean Society of Lipid & Atherosclerosis, were enrolled. Participants were administered 20 mg of atorvastatin daily for the first 8 weeks, and if the targeted low-density lipoprotein cholesterol (LDL-C) level was not achieved, the dose was increased to 40 mg for the second 8 weeks. The primary endpoint was percentage change of LDL-C from baseline after 16 weeks of drug administration.ResultsForty-four women were enrolled, 28 of whom (75.6%) had diabetes mellitus. By the end of treatment period (16 weeks) all patients had achieved LDL-C target levels, with 33 (94.2%) of the participants achieving it after only 8 weeks of administration. After 16 weeks, LDL-C decreased by 45.8±16.7% (p<0.001) from the baseline, and total cholesterol (33.2±10.9%; p<0.001), triglyceride (24.2±37.5%; p=0.001), and apolipoprotein B (34.9±15.6%; p<0.001) also significantly decreased. Blood glucose and liver enzyme levels slightly increased, but none of the participants developed serious adverse events that would cause them to prematurely withdraw from the clinical trial.Conclusion20 and 40 mg atorvastatin was effective and safe for treating dyslipidemia in postmenopausal Korean women with moderate-to-high cardiovascular risk.

Cardiovascular event rates and trajectories of LDL-cholesterol levels and lipid-lowering therapy in patients with atherosclerotic cardiovascular disease: A population-based cohort study

BackgroundAn understanding of cardiovascular event rates and low-density lipoprotein cholesterol (LDL-C) levels and trajectories in patients with atherosclerotic cardiovascular disease is needed to evaluate treatment goals and adherence to guidelines. MethodsWe conducted a population-based cohort study in the North and Central Denmark Regions. Patients with prevalent atherosclerotic cardiovascular disease (myocardial infarction, non-hemorrhagic stroke, or peripheral artery disease) during 2006–2009 were identified. All patients received lipid-lowering therapy (statins or ezetimibe) and had LDL-C levels ≥1.8 mmol/L at baseline (January 1, 2010). We followed patients for 6 years until a primary composite outcome of cardiovascular death, myocardial infarction, non-hemorrhagic stroke, hospitalization for unstable angina, or coronary revascularization. Additionally, we characterized changes in LDL-C levels and use of statins during follow-up. ResultsThe study included 10,772 patients (median age 69.2 years, 60.4% male). The overall event rate for the primary outcome was 62.7 (95% confidence interval: 59.2–66.2) per 1000 person-years. This event rate was higher among men than among women and increased with age and baseline LDL-C levels. Approximately 25% of patients with LDL-C measurements during follow-up achieved LDL-C levels below 1.8 mmol/L. Of the approximately two-thirds of patients using statins at the end of follow-up, nearly all patients (97%) received high-intensity therapy. ConclusionsIn this population of patients with atherosclerotic cardiovascular disease, we found high cardiovascular event rates, which increased with baseline LDL-C levels. Although most patients were on high-intensity statin therapy at end of follow-up, only one-quarter reached the guideline-recommended target LDL-C level ≤ 1.8 mmol/L.

Fixeddose combination of rosuvastatin + ezetimibe: ease of use, safety and efficacy

Today, cardiovascular diseases remain the leading cause of morbidity and mortality globally. Hyperlipidemia and dyslipidemia are key points in the occurrence and progression of CVDs, as well as the development of its complications. Elevated low density lipoprotein cholesterol (LDL-C) is the target of lipid-lowering therapy. The LDL-C target level is often not achieved in everyday clinical practice, which is especially important for patients at high and very high risk for cardiovascular complications. Furthermore, in some patient subgroups, atherogenic dyslipidemia is observed. Due to use of intensive and prolonged lipid-lowering therapy, the problem of its tolerability and patient adherence to the treatment becomes a live issue today. In addition, the use of drugs with effect that complements and enhances the effect of statin helps to achieve targets and improve long-term prognosis. Statins and ezetimibe are effective and widely used drugs to treat dyslipidemia. Clinical studies show that ezetimibe can be safely co-administered with statins to enhance lipid-lowering activity. In this regard, a statin and non-statin drug fixed-dose combination tablet may have additional advantages both for enhancing the lipidlowering effect and for greater patient convenience. Rosuvastatin is more effective than other statins in reducing low density lipoprotein cholesterol. The article provides a rationale for the possibility, efficacy, safety and convenience of using an ezetimibe and rosuvastatin fixed-dose combination tablet in patients with a high and very high risk and unattained target level of low density lipoprotein cholesterol.

P828Low-density lipoprotein cholesterol lowering therapy and target level attainment after a recent myocardial infarction - nationwide cohort study

Abstract Background Lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk of cardiovascular disease after a myocardial infarction (MI). The European Society of Cardiology (ESC) guidelines recommend lipid lowering therapy to reach LDL-C treatment targets after an MI. Purpose To assess LDL-C target level attainment according to the ESC guidelines among patients with a recent MI in Sweden. Methods We used data from nationwide registers in Sweden and included patients aged 18–74 years admitted to a hospital with MI (1 January 2013–1 October 2016). Among patients who were alive and had LDL-C data available, we assessed LDL-C target achievement at 6–10 weeks (n=21,505) and 12–14 months (n=17,957) after the MI by category of lipid lowering therapy (no statin; low/moderate-intensity statins; high-intensity statins; any statin plus ezetimibe). The target was defined as an LDL-C of &lt;1.8 mmol/L and a ≥50% reduction from the baseline if LDL-C was 1.8–3.5 mmol/L and the patient was not already receiving statins. Results Most patients were treated with high-intensity statin monotherapy (84.2% and 72.0%) or any statin with ezetimibe (2.1% and 10.4%) at 6–10 weeks and 12–14 months after the MI, respectively. In total, 37.7% (6–10 weeks) and 38.3% (12–14 months) had attained their LDL-C target. The proportion of patients attaining their LDL-C target at 6–10 weeks was 12% (no statin), 30% (low/moderate-intensity statins), 39% (high-intensity statins), and 49% (any statin plus ezetimibe). The corresponding numbers at 12–14 months were 16% (no statin), 29% (low/moderate-intensity statins), 39% (high-intensity statins), and 58% (any statin plus ezetimibe). A total of 11.8% at 6–10 weeks and 12.3% at 12–14 months reached an LDL-C level of &lt;1.8 mmol/L, but did not reach their LDL-C target level due to the ≥50% reduction criteria. (Figure 1) Figure 1 Conclusions In this large population-based study using nationwide data, more than half of patients with a recent MI did not achieve the ESC guidelines LDL-C target levels, despite a large proportion with high-intensity statin therapy. In patients treated with statins and ezetimibe, four out of ten did not reach the ESC LDL-C target level. Our findings indicate that there may be a need for additional LDL-C lowering therapy if the target level is to be attained in all patients. Acknowledgement/Funding This project was supported by funding from Merck Sharp &amp; Dohme.

Efficiency and problems of statin therapy in patients with heterozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is associated with a very high risk of cardiovascular complications and the need for an early aggressive lipid-lowering therapy. The achievement of lipid target levels is often an extremely difficult task in these patients. Aimsto analyze sex and age structure of ischemic heart disease (IHD) in patients with a definite, possible and probable FH. to assess the degree of achievement of low density lipoprotein cholesterol (LDL-C) target levels in FH patients on statin therapy and complications that occur during therapy; to analyze the adherence of FH patients to statin therapy and reveal the factors which have an influence on it. Materials and methodsThe analysis of IHD clinical characteristics was performed in 253 FH patients from Karelian register, mean age 52.5 years (confidence interval, CI 22.0; 78.0). Using Dutch Lipid Clinic Network Criteria (DLCN), we established the diagnosis of FH as “definite” if the total number of points was more than eight, “probable” – if the number of points was 6–8, “possible” if the number of points was 3–5. The diagnosis was considered to be excluded if the score was less than three. A definite FH was diagnosed in 96 patients.For the evaluation of target LDL-C levels achievement on statin therapy we analyzed data from 191 FH patients (75 males). For the evaluation of adherence to statin therapy Morisky-Green questionnaire was used in 93 definite FH patients. ResultsIn the group with a definite FH the incidence of IHD in the age range from 39 to 60 years was higher in women than in men (50% and 39.4%, p > 0.05), in patients older than 60 years IHD was observed in 66.7% of women and 50% of men (p > 0.05). In general, in the group with a definite FH, the frequency of IHD was more than three times higher in the age group over 40 years compared with patients under 40 years.57% of patients with a definite FH were adherent to lipid-lowering therapy, 16% had partial adherence and no adherence to therapy was documented in 27% of patients. The achievement of LDL-C target levels was 19.2%: 22.6% in definite FH group and 12.5% in possible FH.Smoking and gender were not associated with adherence to statin therapy. Associated factors with increased adherence to statin therapy were age (p = 0.000003), arterial hypertension (OR = 1.90 (1.02; to 3.55), p = 0.044), the history of IHD (OR = 2.99 (1.50; of 5.97) p = 0.002), myocardial infarction (OR = 5.26 (2.03; 13.60), p = 0.0006), myocardial revascularization (OR = 20.3 (2.64; 156.11), p = 0.004) and the fact of target LDL-cholesterol levels achievement (OR = 19.93 (7.03; 56.50), p < 0.0001).The main reason for the non-acceptance of statin therapy for FH patients was the fear of side effects in 87%. The main reasons for stopping current statin intake were myalgia in 12%, an increase in transaminases in 35%, skin rashes in 12%, and high cost in 6%. 29% of patients had made the decision to stop therapy themselves. Conclusionsthe frequency of IHD in FH patients was more than three times higher in the age group over 40 years and was higher in women. In clinical practice statin therapy in FH patients rarely reaches target lipid values, one of the reasons was low adherence to statin therapy.

Strategies to Overcome Residual Risk During Statins Era.

At present, atherosclerosis is one of the most important field in clinical and research medicine. Because it is closely related to cardiovascular (CV) and endocrine disorders such as coronary artery disease, cardiometabolic disorders, much research on how to manage atherosclerosis has been performed. The low-density lipoprotein cholesterol (LDL-C) concentration has been established as an independent risk factor for developing atherosclerosis, and considerable effort has been committed to educating both physicians and the general public on the importance of lowering LDL-C with statins. Although statins have already significantly improved CV outcomes, patients with LDL-C target levels achieved by intense statin therapy still have significant remaining CV risk. Statins already play a central role in managing hyperlipidemia; however, residual risk with statins is an important field of managing remaining CV risk. Recent studies have suggested residual cholesterol and inflammation risks in causing CV events. In the current review, we will discuss residual risk and suggest strategies to overcome it in the statins era.