Low-density Lipoprotein Cholesterol Goal Research Articles

†Efficacy and Safety of Inclisiran in Patients with Established Cerebrovascular Disease: Pooled Post hoc Analysis of the Phase 3 ORION-9, ORION-10, and ORION-11 Randomized Controlled Trials

<h3>Lead Author's Financial Disclosures</h3> Wolfgang Koenig, MD has received consulting fees and lecture fees from AstraZeneca, Novartis and Amgen; consulting fees from Pfizer, the Medicines Company, DalCor Pharmaceuticals, Genentech, Esperion, OMEICOS, Novo Nordisk, LIB Therapeutics, Kowa, Corvidia Therapeutics and Daiichi Sankyo; lecture fees from Berlin- Chemie, Bristol-Myers Squibb and Sanofi; and grant support and provision of reagents from Singulex, Abbott, Roche Diagnostics and Dr. Beckmann Pharma. <h3>Study Funding</h3> Novartis Pharma AG, Basel, Switzerland. <h3>Background/Synopsis</h3> Patients with hyperlipidemia and established cerebrovascular disease (CeVD) are at increased risk of future strokes or other cardiovascular events (1). In ischemic stroke survivors, statins and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce recurrent cardiovascular events, including stroke (2,3). With guidelines advocating increasingly lower low-density lipoprotein cholesterol (LDL-C) goals, adding lipid-lowering therapies to statins may be needed. Inclisiran, a first-in-class small interfering RNA targeting PCSK9 messenger RNA, when added to maximally tolerated statin therapy for patients with established CeVD, may provide further LDL-C lowering, with a convenient, infrequent dosing schedule (4). <h3>Objective/Purpose</h3> To assess the efficacy and safety of inclisiran in patients with established CeVD. <h3>Methods</h3> This was a post hoc analysis of patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease or its risk equivalents and established CeVD (ischemic stroke, carotid artery stenosis by angiography or ultrasound greater than 70%, and/or percutaneous or surgical carotid artery revascularization) from ORION-9 (NCT03397121), ORION-10 (NCT03399370), and ORION-11 (NCT03400800), randomized 1:1 to receive inclisiran sodium 300 mg (equivalent to 284mg inclisiran) or placebo at Day 1, Day 90, and 6 monthly thereafter to Day 540. Evaluations included LDL-C percentage change from baseline to Day 510 and corresponding time-averaged percentage change from baseline after Day 90 to Day 540; safety was assessed over 540 days. <h3>Results</h3> Of 202 patients with established CeVD at baseline, 90.0% (99/110) of patients receiving inclisiran and 84.8% (78/92) on placebo reported prior ischemic stroke; others reported prior carotid artery stenosis and/or carotid revascularization (Table 1). Mean (95% CI) placebo- corrected LDL-C percentage change from baseline at Day 510 with inclisiran was −55.2% (−64.5 to −45.9); corresponding time-averaged change from baseline between Days 90 and 540 was −55.2% (−62.4 to −47.9) (P less than 0.0001 for both; Table 2). Treatment-emergent adverse events (TEAEs) and serious TEAEs were more frequent with inclisiran vs placebo. Clinically relevant injection site TEAEs were more frequent with inclisiran (3.6% [4/110]) vs placebo (0% [0/92]) and none was severe. Few patients had clinically relevant laboratory measurements (Table 2). <h3>Conclusions</h3> In patients with established CeVD, twice-yearly dosing with inclisiran (after the initial and 3-month doses) provided a sustained additional LDL-C reduction of ∼55% and a modest increase in mild/moderate injection site TEAEs. The cardiovascular benefits of inclisiran in patients with established CeVD are being evaluated in ongoing trials.

Attainment of low-density lipoprotein cholesterol goals in statin treated patients: Real-world evidence from Australia.

Little is known about the attainment of low-density lipoprotein cholesterol (LDL-C) targets in patients treated with statins in Australian primary healthcare setting that are at increased risk of cardiovascular disease. A retrospective cohort study was conducted using data from electronic medical records of patients treated by general practitioners across Australia. LDL-C target attainment was defined as LDL-C levels ≤ 2 mmol/L for all risk groups, in line with Australian guidelines. Multivariable logistic regression was used to identify the factors associated with LDL-C target attainment. Overall, 61,407 patients were included in the analysis. The mean age was 65 years (± standard deviation [SD] 12.1); 52.0% were males.. Overall, the median LDL-C level was 2.3 mmol/L (IQR = 1.8 - 2.8) and 36.0% of the study population met therapeutic targets. Increased likelihood to achieve LDL-C targets was observed in patients diagnosed with type 2 diabetes (OR 2.07, 95% CI 1.92 - 2.24), stroke (OR = 1.58, 95% CI 1.39 - 1.79, P < 0.001) or chronic heart disease (OR = 1.67, 95% CI 1.55 - 1.81, P < 0.001). Patients diagnosed with dyslipidemia (OR = 0.59, 95% CI 0.55 - 0.64, P < 0.001), hypertension (OR = 0.91, 95% CI 0.83 - 1.00, P < 0.05) and current smokers (OR = 0.71, 95% CI 0.71 - 1.00, P < 0.05), were less likely to attain LDL-C targets, regardless of the type, intensity and length of use of the prescribed statin. Longer duration and higher intensity statin were associated with more patients achieving targeted LDL-C goal, however nearly two thirds of Australians still failed to achieve targeted outcome even after 24 months of statin therapy.

Combination Therapy of Ezetimibe and Rosuvastatin for Dyslipidemia: Current Insights.

Cardiovascular disease is one of the leading causes of death around the world with various efforts being made to reduce risk in patients through preventive measures. One major method for prevention has been managing cholesterol, particularly low-density lipoprotein to decrease atherosclerotic plaque burden, potentially decreasing future cardiac complications. Statins have been the gold standard therapy for hypercholesterolemia treatment due to their ease of dosing, limited drug interactions, and favorable safety profile. Unfortunately, statin therapy alone is not always effective enough to adequately control a patient’s elevated lipid levels and combination therapy may be warranted. Ezetimibe is commonly added to regimens to help augment cholesterol lowering by inhibiting the absorption of cholesterol. The recent approval of a combination tablet of high-intensity rosuvastatin and ezetimibe has introduced a potentially more beneficial option for cholesterol management in addition to the only available combination of moderate intensity simvastatin and ezetimibe. We aimed to identify potential beneficial effects of ezetimibe by comparing its use in combination with high-intensity rosuvastatin compared to a statin therapy alone or in combination with moderate intensity simvastatin through a literature review. The current evidence indicated that combination therapy outperformed statin monotherapy in reduction of low-density lipoprotein cholesterol and patients were more likely to achieve their target low-density lipoprotein cholesterol goal level. This suggests rosuvastatin/ezetimibe combination holds a potential place in therapy for patients requiring a more aggressive reduction in cholesterol to help prevent atherosclerotic disease.

Lowering LDL cholesterol in clinical practice: time for change?

Atherosclerotic cardiovascular disease (ASCVD) events are associated with cumulative exposure to LDL cholesterol. Clinical guidelines for blood cholesterol management in people with ASCVD recommend monotherapy with the highest tolerated dose of statin before consideration of additional non-statin therapy to reach the LDL cholesterol goal.1,2 Combination lipid-lowering therapy (LLT) reduces LDL cholesterol concentrations to a greater extent than doubling the statin dose.3 However, until now, no randomised clinical trial had compared the long-term clinical event outcomes of high-intensity statin monotherapy versus lower-intensity statin with ezetimibe.

Cholesterol-Lowering Therapy in Patients at Low-to-Moderate Cardiovascular Risk.

Elevated low-density lipoprotein cholesterol (LDL-C) is unanimously recognized as a major modifiable risk factor related to the development of atherosclerotic cardiovascular disease (ASCVD). Consistent evidence confirms that reducing LDL-C is associated with reduction of major adverse cardiovascular events (MACEs), with benefits proportionally related to initial individual CV risk and absolute reduction of LDL-C levels. The recent European guidelines on cardiovascular prevention have proposed a revised approach in cardiovascular risk evaluation, taking into account a renewed consideration of the interaction between risk factors and possible confounding factors (e.g., age). Although for patients considered to be at high and very high cardiovascular risk the need for stringent risk factors treatment is clearly stated, for those who are at low-to-moderate cardiovascular risk the issue is more debated. For those latter subjects, current guidelines indicate that risk factor treatment is generally not necessary, unless the impact of CV risk modifiers, lifetime CV risk and treatment benefit may be substantial. In addition, despite the estimated low-to-moderate short-term CV risk, the early appearance of even mild LDL-C level elevations may contribute to impair long-term CV prognosis. Therefore, encouraging the achievement of desired LDL-C goals through tailored conservative lifestyle changes and, if necessary, pharmacologic strategies should not be excluded categorically in all low-to-moderate risk individuals. In this review, we summarize the most recent evidence that may influence the choice to treat or not to treat LDL-C elevations in subjects at low-to-moderate risk and the suggested therapeutic tools aimed at achieving the recommended LDL-C goals.

Sex Difference in Control of Low-Density Lipoprotein Cholesterol in Older Patients after Acute Coronary Syndrome.

Objective. The main aim of this study is to examine the achievement of low-density lipoprotein cholesterol (LDL-C) targets in older patients after acute coronary syndrome (ACS), and the secondary aim is to examine sex difference in LDL-C target achievement. Methods. Patients aged ≥60 years with ACS admitted to a tertiary hospital in Vietnam were recruited from December 2019 to August 2020. LDL-C target achievement was defined as having an LDL-C goal of <1.8 mmol/L. Multivariate logistic regression was applied to investigate the predictive factors for LDL-C target achievement. Results. A total of 232 participants were included in this study (mean age 75.5 years, 40.1% were women). Participants had an average of three chronic conditions other than coronary heart disease. All participants were prescribed statin monotherapy at discharge (59.5% on high-intensity statins). After 3 months, 218 (94.0%) of the participants were on statin monotherapy, 14 (6.0%) were on statin combined with ezetimibe. The proportion of participants that achieved LDL-C target after 3 months was 56.5% (40.9% in women and 66.9% in men, p < 0.001). On univariate logistic regression, women were less likely to achieve their LDL-C target compared to men (unadjusted OR 0.34, 95% CI 0.20–0.59). This association was still significant in the adjusted model (adjusted OR 0.43, 95% CI 0.24–0.78). Other factors that were significantly associated with LDL-C target achievement included age, smoking, sedentary lifestyle, LDL-C level on admission, history of using statin before admission, and high-intensity statin prescribed at discharge. Conclusions. Our study found that nearly a half of older patients with ACS did not achieve their LDL-C target after 3 months, and suboptimal control of LDL-C was more common in women.

Combined lipid goal attainment in patients with type 2 diabetes and dyslipidemia: A head-to-head comparative trial of statins.

This study compared the efficacy of two statin treatments (simvastatin vs rosuvastatin) in achieving the combined goal of low-density lipoprotein cholesterol (LDL-C) <2.6 mmol/L and non-high-density lipoprotein cholesterol (non-HDL-C) <3.4 mmol/L in patients with type 2 diabetes and dyslipidemia. After a 5-week run-in, 89 patients with type 2 diabetes having fasting triglyceride (TG) levels of 1.7 to 5.7 mmol/L or non-HDL-C levels of 3.4 to 5.2 mmol/L were randomized to receive simvastatin 20 mg daily for 4 weeks followed by 40 mg for 8 weeks or rosuvastatin 10 mg for 4 weeks followed by 20 mg for 8 weeks. The primary end-point was the percentage of patients achieving the combined goal at week 12. Although significant between-group differences were observed in changes in LDL-C and non-HDL-C levels, both study treatments were sufficiently intensive for a 40% to 55% LDL-C reduction. At the end of the study, the two groups had similar percentages of patients who achieved the combined lipid goal (84% vs 89%, p = 0.66). All patients who attained the combined lipid goal also met the apolipoprotein B (Apo-B) target of <0.9 g/L. No between-group differences were noted in changes in HDL-C and TG levels at week 12. The patients tolerated both treatments well. In our study, ≈85% of patients with type 2 diabetes and dyslipidemia could achieve the combined lipid goal with statin monotherapy. The two statin treatments could sufficiently control diabetic dyslipidemia (NCT00506961).

Achievement of ESC/EAS LDL-C treatment goals after an acute coronary syndrome with statin and alirocumab.

European guidelines set low-density lipoprotein cholesterol (LDL-C) treatment goals &lt;1.4 mmol/L after acute coronary syndrome (ACS), and &lt;1.0 mmol/L for patients with recurrent cardiovascular events ≤2 years. Many ACS patients do not achieve these goals on statin alone. We examined actual goal achievement with alirocumab and projected achievement with ezetimibe, either added to optimized statin therapy. The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18 924 patients with recent ACS and hyperlipidaemia despite high-intensity or maximum-tolerated statin therapy. This subanalysis comprised 17 589 patients with LDL-C ≥1.4 mmol/L at baseline who did not receive ezetimibe treatment. High-intensity statin treatment was used in 88.8%. Median (interquartile range) baseline LDL-C was 2.3 (1.9-2.7) mmol/L. With alirocumab, 94.6% of patients achieved LDL-C &lt;1.4 mmol/L at ≥1 post-baseline measurement vs. 17.3% with placebo. Among 2236 patients with a previous cardiovascular event within 2 years (before the qualifying ACS), 85.2% vs. 3.5%, respectively, achieved LDL-C &lt;1.0 mmol/L. Among patients not treated with ezetimibe, we projected that its use would have achieved LDL-C &lt;1.4 and &lt;1.0 mmol/L in 10.6 and 0%, respectively, at baseline (assuming 18 ± 3% reduction of LDL-C). Among patients with recent ACS and LDL-C ≥1.4 mmol/L despite optimized statin therapy, the addition of alirocumab allowed 94.6% to achieve the 2019 European guideline LDL-C goal &lt;1.4 mmol/L, and 85.2% of those with recurrent cardiovascular events to achieve &lt;1.0 mmol/L. In contrast, the addition of ezetimibe to optimized statin therapy was projected to achieve LDL-C &lt;1.4 mmol/L in only 10.6% of patients at baseline.

Achieving Lower LDL-C Levels After a Recent Myocardial Infarction Might Be Associated with Lower Healthcare Resource Use and Costs in Spain.

IntroductionThere is little evidence on the relationship between achieved low-density lipoprotein cholesterol (LDL-C) levels and costs in patients on lipid-lowering therapy (LLT). We described healthcare resource use and costs (direct and indirect) by achieved LDL-C in patients receiving LLT after a recent myocardial infarction (MI) in Spain.MethodsThis was a retrospective observational study of anonymized electronic medical records from seven regions in Spain (BIG-PAC® database; n = 1.9 million). Eligible patients were adults (≥ 18 years) hospitalized for an MI between January 2015 and December 2017, treated with a statin and/or ezetimibe, and having recorded LDL-C values at baseline and during follow-up. Healthcare resource use and direct and indirect costs (in 2018, €) were described by achieved LDL-C levels during a follow-up of 18 months.ResultsOf 6025 patients (mean age, 69.7 years; 77% male), only 11% achieved LDL-C goals as defined in the 2016 ESC/EAS guidelines (< 70 mg/dL), and just 1% reached the lower target (< 55 mg/dL) in the current 2019 guidelines. Achieving lower LDL-C levels translated to lower healthcare resource use and costs. Mean total (direct and indirect) costs ranged from €5044 for patients with LDL-C < 55 mg/dL to €7567 for patients with LDL-C ≥ 130 mg/dL.ConclusionVery few patients achieved recommended LDL-C goals despite using LLT. Achieving lower LDL-C levels after an MI might be associated with lower healthcare resource use and costs. Use of more intensive LLT, leading to greater reductions in LDL-C, could therefore be beneficial both from a clinical and an economic perspective.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02187-1.

Attainment of low-density lipoprotein cholesterol goals in patients treated with combination therapy: A retrospective cohort study in primary care

The attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in real-world settings among patients receiving combination lipid-lowering therapy (LLT, statins plus non-statins) is not well characterised. To evaluate LDL-C levels and LDL-C goal attainment in patients treated with combination LLT in real-world primary care settings. A retrospective cohort study of patients treated with combination LLT. Data were drawn from general practitioner electronic medical records across Australia from 2013 to 2019. The on-treatment goal for LDL-C was < 2 mmol/L (77 mg/dL), as per Australian guidelines. The cohort analysed included 9,173 individuals treated with combination LLT. The mean age was 65.8 years (standard deviation [SD] 11.5), 60.1% were males, and 56.7% had at least one cardiovascular risk factor. The median on-treatment LDL-C was 2.1 mmol/L (IQR 1.6-2.8), and overall 45.4% of the cohort met LDL-C goals, with individuals on fixed-dose combination of statins plus ezetimibe having the highest rates of achievement (49.8%). In multivariable logistic regression analyses, factors associated with LDL-C goal achievement were male sex (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.3-1.6, p < 0.001), aged >80 years (OR 4.2, 95% CI 1.5 - 6.6, p=0.006), and a history of T2DM (OR 1.7; 95% CI 1.5-1.9, p < 0.001) or coronary heart disease (OR 1.4, 95% CI 1.2 - 1.6, p < 0.001). More than half of Australians on combination LLT did not achieve LDL-C goals. Urgent measures are needed to address this gap in clinical practice to minimise negative health outcomes.

Bempedoic acid and PCSK9 inhibitor eligibility in a contemporary population with atherosclerotic cardiovascular disease

Abstract Funding Acknowledgements Type of funding sources: None. Background and Purpose The reduction of low-density lipoprotein cholesterol (LDL-C) in patients with established coronary heart disease (CHD) reduces the risk of atherosclerotic cardiovascular disease (ASCVD) events.(1) Many CHD patients fail to achieve guideline-recommended LDL-C targets without prohibitively expensive proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors).(2, 3, 4) This study aims to assess the impact that bempedoic acid may have on PCSK9 inhibitor eligibility in a population with CHD and ascertain whether its universal adoption would lead to overall cost-savings and a cost-effective reduction in ASCVD events. Methods and Results This retrospective analysis included 635 participants from the iASPIRE study, which recently assessed secondary prevention in an Irish cohort of CHD patients. We applied the 2019 ESC/EAS dyslipidaemia guideline LDL-C target of &amp;lt;1.4mmol/L and simulated the average treatment effect of improved lipid-lowering therapy with statins, ezetimibe and bempedoic acid. 86.3% of iASPIRE participants did not have LDL-C control and qualified for treatment intensification. Optimisation of statin therapy would allow 24.4% of patients to achieve their LDL-C goal, while the addition of ezetimibe would improve this to 55.7% leaving 44.3% eligible for a PCSK9 inhibitor. Utilising bempedoic acid would further reduce the proportion eligible to 18.7%. Based on current market prices and the universal application of ESC/EAS recommendations,(1, 5) the adoption of bempedoic acid would reduce the annual treatment costs associated with PCSK9 inhibitor use by almost 50% and result in cost savings per prevented CVD event. Conclusions The vast majority of CHD patients currently fail to achieve the recommended LDL-C target in everyday clinical practice. Ezetimibe and optimised statin therapy would enable most patients to meet their LDL-C goal. Employing bempedoic acid in patients with poor LDL-C control would significantly reduce the requirement for PCSK9 inhibitors and lead to cost savings per prevented CVD event.

Comparison of Low-Density Lipoprotein Cholesterol (LDL-C) Goal Achievement and Lipid-Lowering Therapy in the Patients With Coronary Artery Disease With Different Renal Functions.

AimThe aim of this study was to evaluate the relationship between renal function and low-density lipoprotein cholesterol (LDL-C) goal achievement and compare the strategy of lipid-lowering therapy (LLT) among the patients with coronary artery disease (CAD) with different renal functions.MethodsIn this study, we enrolled 933 Chinese patients with CAD from September 2020 to June 2021 admitted to the Cardiometabolic Center of Fuwai Hospital in Beijing consecutively. All individuals were divided into two groups based on their estimated glomerular filtration rate (eGFR). The multiple logistical regression analysis was performed to identify and compare the independent factors which impacted LDL-C goal achievement in the two groups after at least 3 months of treatment.ResultsThere were 808 subjects with eGFR ≥ 60 ml/min/1.73 m2 who were divided into Group 1 (G1). A total of 125 patients with eGFR <60 ml/min/1.73 m2 were divided into Group 2 (G2). The rate of LDL-C goal attainment (LDL-C <1.4 mmol/L) was significantly lower in G2 when compared with that in G1 (24.00% vs. 35.52%, P = 0.02), even though there was no significant difference in the aspect of LLT between the two groups (high-intensity LLT: 82.50% vs. 85.60% P = 0.40). Notably, in G1, the proportion of LDL-C goal achievement increased with the intensity of LLT (23.36% vs. 39.60% vs. 64.52% in the subgroup under low-/moderate-intensity LLT, or high-intensity LLT without proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (PCSK9i), or high-intensity LLT with PCSK9i, respectively, P < 0.005). In addition, in G2, there was a trend that the rate of LDL-C goal achievement was higher in the subgroup under high-intensity LLT (26.60% in the subgroup under high-intensity LLT without PCSK9i and 25.00% in the subgroup under high-intensity LLT with PCSK9i) than that under low-/moderate-intensity LLT (15.38%, P = 0.49). Importantly, after multiple regression analysis, we found that eGFR <60 ml/min/1.73 m2 [odds ratio (OR) 1.81; 95%CI, 1.15–2.87; P = 0.01] was an independent risk factor to impact LDL-C goal achievement. However, the combination strategy of LLT was a protective factor for LDL-C goal achievement independently (statin combined with ezetimibe: OR 0.42; 95%CI 0.30–0.60; P < 0.001; statin combined with PCSK9i: OR 0.15; 95%CI 0.07–0.32; P < 0.001, respectively).ConclusionImpaired renal function (eGFR <60 ml/min/1.73 m2) was an independent risk factor for LDL-C goal achievement in the patients with CAD. High-intensity LLT with PCSK9i could improve the rate of LDL-C goal achievement significantly. It should be suggested to increase the proportion of high-intensity LLT with PCSK9i for patients with CAD, especially those with impaired renal function.

Mathematical modelling of the most effective goal of cholesterol-lowering treatment in primary prevention

ObjectiveTo compare quantitatively different recommended goals for cholesterol-lowering treatment in the primary prevention of atherosclerotic cardiovascular disease (ASCVD).DesignOutcomes at pretreatment low-density lipoprotein (LDL) cholesterol concentrations from 2 to 5 mmol/L...

Léčba hypertenze a dyslipidemie po cévní mozkové příhodě

Stroke is the second most common cause of mortality worldwide and the third most common cause of disability. Arterial hypertension is the most prevalent risk factor for stroke. A precise management of arterial hypertension prevents the first episode of stroke and the recurrence. Blood pressure must be decreased carefully and not very vigorously in the acute phase of the stroke. Recommended blood pressure goals in chronic tratment are at least 140 / 90 mm Hg and lower if tolerated. ACE inhibitors or angiotensin receptor blockers in combination with calcium channel blockers or indapamide are favorable antihypertensive drugs. Dyslipidemia is also a strong risk factor for ischaemic stroke and has no relatioship to the other etiologies of stroke. The cardiovascular risk in patients after a stroke is very high. An intensive hypolipidemic treatment by statins, ezetimibe and PCSK9i to LDL-cholesterol goals &lt; 1,4 mmol/l and a 50% decrease was proved to decrease the incidence of recurrent stroke.

Advancements in the Treatment of Homozygous Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder with extreme elevations of low-density lipoprotein cholesterol (LDL-C) leading to premature atherosclerotic cardiovascular disease (ASCVD) as early as in childhood. Management of HoFH centers around aggressive and adequate reduction of LDL-C levels to slow the trajectory of ASCVD development. Historically, lowering LDL-C levels in HoFH has been challenging because of both the markedly elevated LDL-C levels (often ＞400 mg/dL) and reduced response to treatment options, such as statins, for which the mechanism of action requires a functional LDL receptor. However, the treatment landscape for HoFH has rapidly progressed over the last decade. While statins and ezetimibe remain first-line treatment, patients often require addition of multiple therapies to achieve goal LDL-C levels. The PCSK9 inhibitors are an important recent addition to the available treatment options, along with lomitapide, bile acid sequestrants, and, possibly, bempedoic acid. Additionally, ANGPTL3 has emerged as an important therapeutic target, with evinacumab being the first available ANGPTL3 inhibitor on the market for the treatment of patients with HoFH. For patients who cannot achieve adequate LDL-C reduction, lipoprotein apheresis may be necessary, with the added benefit of reducing lipoprotein(a) levels that carries an added risk if also elevated in patients with HoFH. Finally, gene therapy and genome editing using CRISPR/Cas-9 are moving through clinical development and may dramatically alter the future landscape of treatment for HoFH.

Lipid-lowering therapy and risk-based LDL-C goal attainment in Belgium: DA VINCI observational study

Background Cardiovascular disease (CVD) is one of the leading causes of death in Belgium. Current strategies for the prevention and management of CVD focus on reducing low-density lipoprotein cholesterol (LDL-C) levels. This analysis assessed whether LDL-C goals, recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines, were being achieved in a Belgian study population. Methods The cross-sectional, observational, DA VINCI study enrolled patients prescribed lipid-lowering therapy (LLT) between 21 June 2017 and 20 November 2018. Data for patients from Belgium were extracted for this country-specific analysis. Primary endpoint was the proportion of patients who achieved 2016 ESC/EAS risk-based LDL-C goals; attainment of 2019 risk-based LDL-C goals was evaluated post hoc. Results Of 497 enrolled patients, 41% were female and mean age was 68 years. Among subjects with an LDL-C measurement on stabilised LLT, moderate-intensity statin monotherapy was the most prescribed LLT regimen (59%). Overall, 63% of patients achieved their risk-based LDL-C goals according to the 2016 ESC/EAS guidelines. Among patients with established ASCVD, risk-based LDL-C goal attainment was higher in patients with peripheral arterial disease (53%) than patients with coronary (37%) and cerebrovascular disease (42%). According to the updated 2019 ESC/EAS guidelines, less than half (41%) of patients achieved their risk-based LDL-C goal. The proportion of primary and secondary prevention patients who achieved 2019 risk-based LDL-C goals was 59% and 18%, respectively. Conclusion These findings reveal a large gap between the LDL-C goals advocated by the ESC/EAS and the levels achieved in routine clinical practice in Belgium.

Novel Pharmaceutical and Nutraceutical-Based Approaches for Cardiovascular Diseases Prevention Targeting Atherogenic Small Dense LDL.

Compelling evidence supports the causative link between increased levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (CVD) development. For that reason, the principal aim of primary and secondary cardiovascular prevention is to reach and sustain recommended LDL-C goals. Although there is a considerable body of evidence that shows that lowering LDL-C levels is directly associated with CVD risk reduction, recent data shows that the majority of patients across Europe cannot achieve their LDL-C targets. In attempting to address this matter, a new overarching concept of a lipid-lowering approach, comprising of even more intensive, much earlier and longer intervention to reduce LDL-C level, was recently proposed for high-risk patients. Another important concern is the residual risk for recurrent cardiovascular events despite optimal LDL-C reduction, suggesting that novel lipid biomarkers should also be considered as potential therapeutic targets. Among them, small dense LDL particles (sdLDL) seem to have the most significant potential for therapeutic modulation. This paper discusses the potential of traditional and emerging lipid-lowering approaches for cardiovascular prevention by targeting sdLDL particles.

Lipid-lowering for the prevention of cardiovascular disease in the new era: A practical approach to combination therapy: Lipid-lowering and combination therapy

Low density lipoprotein-cholesterol (LDL-C) is the main etiologic factor for the development and progression of atherosclerotic cardiovascular disease (ASCVD) and LDL-C reduction is a central tenet of ASCVD treatment and prevention. Moreover, ASCVD risk reduction is proportional to the magnitude of LDL-C lowering. Recent European guidelines have recommended a goal of &lt;55 mg/dL (&lt;1.4 mmol/L) for patients at very-high cardiovascular risk, while the U.S. guideline considers an LDL-C ≥70 mg/dL (≤1.8 mmol/L) as a threshold to intensify therapy with the addition of a non-statin therapy to statins. To reach these lower LDL-C goals of &lt;55 mg/dL or &lt;70 mg/dL, combination therapy is necessary in the majority of these patients. Drug combinations, and in particular single-pill combinations, may substantially increase adherence to therapy. Adherence is essential for achieving a clinical benefit and, as many patients discontinue medications, the long-term adherence to lipid-lowering therapy represents a major issue in ASCVD prevention. Secondary prevention or high-risk primary prevention patients, such as those with familial hypercholesterolemia in whom maximally-tolerated statin doses alone would not be anticipated to sufficiently lower LDL-C, would benefit from combination therapy. In current clinical practice, statins with ezetimibe, statins plus PCSK9 inhibitors (with or without ezetimibe), and, most recently statins or ezetimibe with bempedoic acid are the most commonly used combination therapies for LDL-C-lowering. This review outlines the importance of using combination therapy for the achievement of LDL-C treatment

Risk stratification and low-density lipoprotein cholesterol goal attainment rates in patients with very high-risk or extreme high-risk atherosclerotic cardiovascular diseases regarding three guidelines

Objective: To explore the differences of risk stratification of very high-risk or extreme high-risk atherosclerotic cardiovascular diseases (ASCVD) and the attainment rates of low-density lipoprotein cholesterol (LDL-C) management targets evaluated by three different criteria, and the causal attributions of these differences. Methods: Patients with ASCVD were consecutively enrolled from January 1 to December 31 in 2019, and were evaluated for very high-risk or extreme high-risk and LDL-C goal attainment rates with 2018 American guideline on the management of blood cholesterol (2018AG), 2019 China Cholesterol Education Program (CCEP) Expert Advice for the management of dyslipidemias (2019EA) and 2020 Chinese expert consensus on lipid management of very high-risk ASCVD patients(2020EC), respectively. The causal attributions of the differences in attainment rates were analyzed as well. Results: A total of 1 864 ASCVD patients were included in this study. According to 2018AG, 2019EA and 2020EC, the proportions of the patients with very high-risk or extreme high-risk were 59.4%, 90.7%, and 65.6%, respectively. The absolute LDL-C target attainment rates were 37.2%, 15.7%, and 13.7%, respectively, the differences between each two rates were statistically significant (all P<0.001). As to the differences in attainment rates between 2020EC and 2018AG, 61.5% were due to the different LDL-C goal attainment values and 38.5% were caused by the different risk stratifications, while for the differences between 2020EC and 2019EA attainment rates, different LDL-C goal attainment values were responsible for 13.2%, and different risk stratifications were responsible for 86.8% of the differences. Conclusions: There are significant differences in the proportions and LDL-C attainment rates among the three different criteria for very high-risk or extreme high-risk ASCVD. 2020EC showed a moderate proportion of patients with extreme high-risk, and had the lowest LDL-C attainment rate. The differences between 2020EC and 2018AG are mainly due to the LDL-C target values, and the differences between 2020EC and 2019EA are mainly caused by the risk stratifications.

Atherosclerotic Cardiovascular Disease Risk and Lipid-Lowering Therapy Requirement in China

BackgroundLipid-lowering therapy (LLT) is one of the key strategies for reducing the atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the percentage of people in need of different LLT regimens to achieve optimal targets of low-density lipoprotein cholesterol (LDL-C), and the corresponding cost and benefit.MethodsWe conducted a simulation study based on the data from the nationwide China PEACE MPP population cohort (2015–2020), from which we included 2,904,914 participants aged 35–75 years from all the 31 provinces in mainland China. Participants were grouped based on their 10-year ASCVD risks, then entered into a Monte Carlo model which was used to perform LLT intensification simulation scenarios to achieve corresponding LDL-C goals in each risk stratification.ResultsAfter standardizing age and sex, the proportions of participants included at low, moderate, high, and very-high risk were 70.8%, 15.6%, 11.5%, and 2.1%, respectively. People who failed to achieve the corresponding LDL-C goals −8.1% at low risk, 19.6% at moderate risk, 53.2% at high risk, and 93.6% at very-high risk (either not achieving the goal or not receiving LLT)—would be in need of the LLT intensification simulation. After the use of atorvastatin 20 mg was simulated, over 99% of the population at low or moderate risk could achieve the LDL-C goals; while 11.3% at high and 24.5% at very-high risk would still require additional non-statin therapy. After the additional use of ezetimibe, there were still 4.8% at high risk and 11.3% at very-high risk in need of evolocumab; and 99% of these two groups could achieve the LDL-C goals after the use of evolocumab. Such LLT intensification with statin, ezetimibe, and evolocumab would annually cost $2.4 billion, $4.2 billion, and $24.5 billion, respectively, and prevent 264,170, 18,390, and 17,045 cardiovascular events, respectively.ConclusionsModerate-intensity statin therapy is pivotal for the attainment of optimal LDL-C goals in China, and around 10–25% of high- or very-high-risk patients would require additional non-statin agents. There is an opportunity to reduce the rising ASCVD burden in China by optimizing LLT.