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Seasonal influenza immunization reduces the risk of cardiovascular events. Patients with established cardiovascular disease (CVD) derive a greater benefit than those without, yet up to 50 % do not take up the immunization. Patient perceptions and beliefs are known to inform immunization behaviors, yet the immunization related beliefs of patients with CVD have not been described. Objective: To describe beliefs, perceptions and behaviors regarding influenza immunization in patients with CVD. Methods: We undertook a cross-sectional, voluntary and anonymous survey of 181 cardiology inpatients and outpatients attending three large hospitals in Victoria. Results: Median age was 64, 35.0 % were female and 24.2 % spoke a language other than English at home. Over one-third-(34.5 %) of respondents did not receive the seasonal influenza immunization in the prior year. Only half (54.2 %) of patients agreed that their heart condition placed them at higher risk of complications and serious illness if they contracted influenza. Nearly a quarter of patients (24.0 %) were concerned about side effects while 1 in 10 patients raised cost as a barrier despite being free-of-charge in Australia. If asked to receive the seasonal influenza immunization, 86 % patients would agree if their cardiologist recommended it. Conclusion: Despite guideline recommendations, most cardiology patients are uninformed of the cardiovascular benefits of seasonal influenza immunization with many unaware they are at higher risk of influenza-related illness. The vast majority of patients would accept the immunization if recommended by their cardiologist highlighting their important role in improving uptake.

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Introduction: Lower statin utilization is reported among women compared to men, however large-scale studies evaluating gender disparities in LDL-C management in individuals with ASCVD and its subtypes remain limited, particularly across age and racial/ethnic subgroups. In this study, we address this knowledge gap using data from a large US healthcare system. Methods: All adult patients with established ASCVD in the Houston Methodist Learning Health System Registry during 2016-2022 were included. Statin use and dose were extracted from the database. The association between gender and statin utilization was evaluated using multivariate logistic regression analyses in patients with ASCVD overall, across ASCVD subtypes, and by age, racial/ethnic subgroups, and socioeconomic risk factors. Results: A total of 97,819 patients with prevalent ASCVD were included. Women with ASCVD had lower utilization of any statin (64.3% vs 72.6 %; p < 0.001) and high-intensity statin (29.8% vs 42.5 % p < 0.001) compared with men. In fully adjusted models, women had 40 % lower odds of any (adjusted odds ratio [aOR]:0.58, 95 % CI 0.57-0.60) and high-intensity statin use (aOR:0.59, 0.57-0.61) relative to men. Women were also less likely to have guideline-recommended LDL-C < 70 mg/dL (30.2% vs 42.7 %; p < 0.01). These differences persisted across age, racial/ethnic and socioeconomic subgroups. Conclusion: Significant gender disparities exist in contemporary lipid management among patients with ASCVD, with women being less likely to receive any and high-intensity statin and achieving guideline defined LDL-C goal compared with men across age and racial/ethnic subgroups. These disparities underscore the need to further understand potential socioeconomic drivers of the observed lower statin uptake in women.

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Cardiovascular (CV) disease is the most common cause of death in Europe. Despite proven benefits, use of lipid-lowering therapy remains suboptimal. Treatment goals are often not achieved, even in patients at high risk with atherosclerotic CV disease (ASCVD). The occurrence of CV events in patients on lipid-lowering drugs is defined as "residual risk", and can result from inadequate control of plasma lipids or blood pressure, inflammation, diabetes, and environmental hazards. Assessment of CV risk factors and vascular imaging can aid in the evaluation and management decisions for individual patients. Lifestyle measures remain the primary intervention for lowering CV risk. Where drug therapies are required to reach lipid treatment targets, their effectiveness increases when they are combined with lifestyle measures delivered through formal programs. However, lipid drug dosage and poor adherence to treatment remain major obstacles to event-free survival. This article discusses guideline-supported treatment algorithms beyond statin therapy that can help reduce residual risk in specific patient profiles while also likely resulting in substantial healthcare savings through better patient management and treatment adherence.

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BACKGROUND AND OBJECTIVE: High Lp(a) levels are a risk factor for ASCVD, however Lp(a) ordering in clinical practice is low. This study examines how race/ethnicity and socioeconomic status influence Lp(a) ordering. METHODS: This is a single center, retrospective study (2/1/2020-6/30/2023) using electronic medical records of adults with at least one personal ICD-10 diagnosis of ASCVD, aortic valve stenosis, resistant hypercholesterolemia (LDL-C >160 mg/dL on statin therapy), and family history of ASCVD or high Lp(a). We evaluated Lp(a) level differences among racial/ethnic groups and sexes. We also assessed associations between diagnosis type, diagnosis number, age at diagnosis, race/ethnicity, socioeconomic score (based on zip codes), public health coverage and the presence of Lp(a) orders. RESULTS: 4 % of our cohort (N=2,249 in 56,833) had an Lp(a) order (17.3 % of whom identified as Hispanic, 8.7 % non-Hispanic Black, 47.5 % non-Hispanic White, and 27 % Asian/other). Non-Hispanic Black and Hispanic patients had lower rates of Lp(a) orders (0.17 % and 0.28 %, respectively) when compared to non-Hispanic White patients (2.35 %), p < 0.001, however, their median Lp(a) levels were higher, p < 0.001. Individuals on Medicaid or belonging to deprived socioeconomic groups were less likely to have an Lp(a) order (IRR = 0.40, p < 0.001 and IRR = 0.39, p < 0.001 respectively). Certain diagnosis (carotid stenosis, family history of ASCVD and FH) and multiple diagnoses (>2) resulted in more Lp(a) orders compared to only one diagnosis (p < 0.001). CONCLUSIONS: Lp(a) ordering is low in patients with or at risk for ASCVD. Non-Hispanic Black and Hispanic patients are less likely to have an Lp(a) order. Individuals on Medicaid and residing in socioeconomically deprived neighborhoods are less like have an Lp(a) order. Lp(a) orders depend on the type and number of patients' diagnoses.

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Cardiovascular disease (CVD) claims millions of lives every year, with atherosclerotic cardiovascular disease (ASCVD) being the main cause. ASCVD treatment includes drug therapy, lifestyle intervention, and Percutaneous Coronary Intervention (PCI) all of which significantly enhance cardiovascular function and reduce mortality. However, hyperplasia can lead to vascular obstruction, worsen angina symptoms, or even cause heart disease, affecting patients' long-term prognosis. Therefore, finding effective ways to combat hyperplasia is crucial for cardiovascular therapy. In recent years, ferroptosis has gained attention as a new form of cell death closely associated with several diseases, including cardiovascular diseases. It involves complex metabolic processes critical for cellular homeostasis and normal function. Abnormal proliferation and phenotypic transformation of vascular smooth muscle cells (VSMC) are crucial mechanisms underlying cardiovascular disease development. Inhibiting ferroptosis in VSMC has the potential to significantly reduce neointima proliferation. Glucagon-like peptide-1 receptor agonist (GLP-1RA) constitutes a widely employed class of hypoglycemic agents with direct implications for the cardiovascular system, mitigating adverse cardiovascular events. Research indicates that the stimulation of GLP-1 holds promise as a therapeutic strategy in mitigating cardiovascular events such as restenosis. Hence, investigating the potential of GLP-1RA as a treatment option for cardiovascular ailments carries immense clinical significance.

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Introduction: The association between a plant-based diet and weight loss and atherosclerotic cardiovascular disease (ASCVD) has not been fully elucidated. We performed a pooled analysis and Mendelian randomization (MR) analysis to investigate this question. Methods: We searched for randomized controlled trials on the effects of a plant-based diet on weight loss compared with a non-plant-based diet. In addition, a two-sample MR study was conducted. IVs were obtained from the genome-wide association studies (GWAS) on the exposures, and we obtained summary statistics on the outcomes. The inverse-variance weighted (IVW) method was used as the main analysis and other MR methods were performed as supplementary analyses. Results: Individuals on the plant-based diet lost more weight than the non-plant-based diet group (WMD -0.96 kg; 95% CI: -1.32 to -0.60). Population conditions and energy restriction were identified as the study-level factors that influenced the pooling results in the subgroup analyses. Increased consumption of raw vegetables was significantly associated with lower BMI (IVW, ß -0.35, 95% CI: -0.62 to -0.08, p = 0.012) and lower risk of obesity (IVW, OR 0.11, 95% CI: 0.01 to 0.99, p = 0.048), coronary heart disease (IVW, OR 0.44, 95% CI: 0.21 to 0.92, p = 0.029) and myocardial infarction (IVW, OR 0.39,95% CI: 0.15 to 0.98, p = 0.045) and a higher HDL-C (IVW, ß 0.47, 95% CI: 0.24 to 0.70, p = 4×10-5). Discussion: The present findings suggest that raw vegetable intake is beneficial for weight loss and prevention of ASCVD.

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BACKGROUND: The ability of a 1-time measurement of non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood (age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear. OBJECTIVES: The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years. METHODS: We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had ≥3 measurements of LDL-C and non-HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non-HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40 years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years. RESULTS: Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995 participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non-HDL-C and LDL-C had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC: 0.93 for the 4 models). The absolute values of non-HDL-C and LDL-C that predicted membership in the top quartiles with the highest simultaneous sensitivity and specificity (highest Youden's Index) were >135 mg/dL for non-HDL-C and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for non-HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non-HDL-C and LDL-C exposure had demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years, respectively, when compared with each bottom quartile. CONCLUSIONS: Single measures of non-HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events.

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CONTEXT: Postprandial lipemia (PPL) is associated with increased risk of endothelial dysfunction (ED), a precursor of atherosclerotic cardiovascular disease (ASCVD). The effects of low-carbohydrate, high-fat (LCHF) diets on ASCVD risk are uncertain; therefore, gaining a greater understanding of LCHF meals on PPL may provide valuable insights. OBJECTIVE: The current systematic review investigated the effects of single LCHF meal consumption on PPL and markers of ED. DATA SOURCES: CINAHL Plus, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for key terms related to endothelial function, cardiovascular disease, glycemia, lipemia, and the postprandial state with no restriction on date. DATA EXTRACTION: Full-text articles were independently screened by 2 reviewers, of which 16 studies were eligible to be included in the current review. All trials reported a minimum analysis of postprandial triglycerides (PPTG) following consumption of an LCHF meal (<26% of energy as carbohydrate). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. DATA ANALYSIS: Single-meal macronutrient composition was found to play a key role in determining postprandial lipid and lipoprotein responses up to 8 hours post-meal. Consumption of LCHF meals increased PPTG and may contribute to ED via reduced flow-mediated dilation and increased oxidative stress; however, energy and macronutrient composition varied considerably between studies. CONCLUSION: Consumption of an LCHF meal had a negative impact on PPL based on some, but not all, single-meal studies; therefore, the contribution of LCHF meals to cardiometabolic health outcomes remains unclear. Further research is needed on specific categories of LCHF diets to establish a causal relationship between postprandial modulation of lipids/lipoproteins and impaired vascular endothelial function. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD 42023398774.

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AIMS: Adding intensive low-density lipoprotein cholesterol (LDL-C)-lowering agents or colchicine to statin has been shown to result in additional cardiovascular benefits for patients with atherosclerotic cardiovascular diseases (ASCVD). We aimed to compare the efficacy and safety of these supplementary agents in patients with ASCVD receiving statin. METHODS: We performed a systematic review and frequentist network meta-analysis of randomized controlled trials. The primary efficacy endpoint was the main adverse cardiovascular event (MACE), and the secondary efficacy endpoints were myocardial infarct, stroke, coronary revascularization, cardiovascular death, and all-cause mortality, respectively. The safety endpoints were treatment discontinuation and non-cardiovascular death. We obtained estimates for efficacy outcomes and safety endpoints and presented these estimates as risk ratio (RR) with 95% confidence intervals. We ranked the comparative efficacy and safety of all drugs with P-scores. RESULTS: Seventeen trials totaling 85,823 participants treated with colchicine (5926 participants), intensive LDL-C lowering (37,854 participants) via proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, Niemann-Pick C1-like 1 protein (NPC1L1) inhibitor or ATP citrate lyase (ACL) inhibitor, or statin alone (42,043 participants) were included. Colchicine was associated with a greater reduction in the risk of MACE (RR 0.72, 0.69-0.91), stroke (RR 0.55, 0.33-0.92), and coronary revascularization (RR 0.73, 0.60-0.90) compared with NPC1L1 inhibitor, and it provided a larger reduction in the risk of MACE (RR 0.79, 0.69-0.91) compared to PCSK9 inhibitor. However, colchicine was associated with increased risk of non-cardiovascular death compared with NPC1L1 inhibitor (RR 1.48, 1.04-2.10) and PCSK9 inhibitor (RR 1.57, 1.08-2.27). Although no regimen prolonged survival, colchicine had worse performance on non-cardiovascular death and all-cause mortality. CONCLUSIONS: In patients with ASCVD receiving statin, colchicine seems to be more effective than intensive LDL-C-lowering therapy with PCSK9 inhibitor or NPC1L1 inhibitor for cardiovascular prevention. However, using colchicine as an alternative to intensive LDL-C-lowering therapy may need to be weighed against the cardiovascular benefits and the potential harms of higher non-cardiovascular death. TRIAL REGISTRATION: PROSPERO Identifier: CRD42023441385.

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INTRODUCTION: The prevalence of tendon rupture and tendinopathies (TRT) has not been determined in a large population of patients with atherosclerotic cardiovascular disease (ASCVD). We investigated TRT prevalence among patients with ASCVD and in the general population, using data from the Symphony Health Integrated Dataverse, a large US medical and pharmacy claims database. METHODS: This retrospective, observational study included patients aged ≥ 19 years from the claims database during the identification period (January 2019 to December 2020) and 12 months of continuous enrollment. The primary outcome was evidence of TRT in the 12 months following the index date (first ASCVD diagnosis in the ASCVD cohort; first claim in the claims database in the overall population). Diagnostic codes (ICD-10 and/or CPT) were used to define ASCVD and TRT diagnosis. RESULTS: The ASCVD cohort and overall population included 5,589,273 and 61,715,843 patients, respectively. In the ASCVD cohort, use of medications with a potential or known association with TRT was identified in 67.9% (statins), 17.7% (corticosteroids), and 16.7% (fluoroquinolones) of patients. Bempedoic acid use was reported in 1556 (< 0.1%) patients. TRT prevalence during 12-month follow-up was 3.4% (ASCVD cohort) and 1.9% (overall population). Among patients with ASCVD, 83.5% experienced TRT in only one region of the body. Factors most associated with TRT in the ASCVD cohort were increasing age, most notably in those aged 45-|64 years (odds ratio [OR] 2.19; 95% confidence interval [CI] 2.07-2.32), obesity (OR 1.51; 95% CI 1.50-1.53), and rheumatoid arthritis (OR 1.47; 95% CI 1.45-1.79). Use of statins or bempedoic acid was not associated with increased TRT risk. CONCLUSION: Patients with ASCVD may have greater risk of TRT than the general population, which may be driven by an increased prevalence of comorbidities and use of medications with a potential or known association with TRT.

Patients with atherosclerosis, the main cause of heart attacks, strokes, and peripheral vascular disease, typically require several drugs to control the disease. Some of the drugs used to treat atherosclerosis have been linked to a higher occurrence of tendon tears (or ruptures) or swelling/inflammation of the tendons (tendinopathies). However, there may be other factors present in these patients that increase the risk of tendon injuries that are not related to these drugs. This study used the medical records of over 5.5 million patients with atherosclerosis and over 63 million patients reflecting the general population in the United States to determine the prevalence of tendon injury. Additionally, the researchers looked at other factors that might be related to a higher risk of tendon injury in each group. Over a 12-month period, tendon injuries occurred in 3.4% of patients with atherosclerosis and 1.8% of patients in the general population. In patients with atherosclerosis, factors such as being obese, older (45­64 years), or having rheumatoid arthritis were also linked to an increased risk of tendon injuries. There was no association seen between statin or bempedoic acid use and tendon injuries. These results may help healthcare providers to determine the underlying risk of tendon injuries and guide treatment of this patient population.

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BACKGROUND: Chronic kidney disease (CKD) poses a substantial burden to individuals, caregivers, and healthcare systems. CKD is associated with higher risk for adverse events, including renal failure, cardiovascular disease, and death. This study aims to describe comorbidities and complications in patients with CKD. METHODS: We conducted a retrospective observational study linking administrative health databases in Alberta, Canada. Adults with CKD were identified (April 1, 2010 and March 31, 2019) and indexed on the first diagnostic code or laboratory test date meeting the CKD algorithm criteria. Cardiovascular, renal, diabetic, and other comorbidities were described in the two years before index; complications were described for events after index date. Complications were stratified by CKD stage, atherosclerotic cardiovascular disease (ASCVD), and type 2 diabetes mellitus (T2DM) status at index. RESULTS: The cohort included 588,170 patients. Common chronic comorbidities were hypertension (36.9%) and T2DM (24.1%), while 11.4% and 2.6% had ASCVD and chronic heart failure, respectively. Common acute complications were infection (58.2%) and cardiovascular hospitalization (24.4%), with rates (95% confidence interval [CI]) of 29.4 (29.3-29.5) and 8.37 (8.32-8.42) per 100 person-years, respectively. Common chronic complications were dyslipidemia (17.3%), anemia (14.7%), and hypertension (11.1%), with rates (95% CI) of 11.9 (11.7-12.1), 4.76 (4.69-4.83), and 13.0 (12.8-13.3) per 100 person-years, respectively. Patients with more advanced CKD, ASCVD, and T2DM at index exhibited higher complication rates. CONCLUSIONS: Over two-thirds of patients with CKD experienced complications, with higher rates observed in those with cardio-renal-metabolic comorbidities. Strategies to mitigate risk factors and complications can reduce patient burden.

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This review explores the many barriers to accessing lipid-lowering therapies (LLTs) for the prevention and management of atherosclerotic cardiovascular disease (ASCVD). Geographical, knowledge, and regulatory barriers significantly impede access to LLTs, exacerbating disparities in healthcare infrastructure and affordability. We highlight the importance of policy reforms, including pricing regulations and reimbursement policies, for enhancing affordability and streamlining regulatory processes. Innovative funding models, such as value-based pricing and outcome-based payment arrangements, have been recommended to make novel LLTs more accessible. Public health interventions, including community-based programs and telemedicine, can be utilized to reach underserved populations and improve medication adherence. Education and advocacy initiatives led by patient advocacy groups and healthcare providers play a crucial role in raising awareness and empowering patients. Despite the barriers to access, novel LLTs present a big opportunity to reduce the burden of ASCVD, emphasizing the need for collaborative efforts among policymakers, healthcare providers, industry stakeholders, and patient advocacy groups to address these barriers to improve access to LLTs globally.

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Background and Objectives: The literature suggests that physiological menopause (MP) seems linked with increased adiposity with a preference for intra-abdominal fat accumulation, greater than what can be attributed only by aging, which could magnify this period's increased cardiovascular risk. Materials and Methods: We retrospectively analyzed two age and body mass index (BMI) propensity-matched subgroups each formed of 90 clinically healthy, 40-60-year-old postmenopausal women, within the first 5 and 5-10 years of MP. The 10-year ASCVD risk was assessed using medical history, anthropometric data, and lipid profile blood tests. The android-to-gynoid (A/G) ratio was computed using Lunar osteodensitometry lumbar spine and hip scans. Results: The A/G ratio was significantly higher for the subgroup evaluated in years 5-10 of MP than in the first 5 years of MP, even after controlling for BMI (1.05 vs. 0.99, p = 0.005). While displaying a significant negative correlation with HDL cholesterol (r = 0.406), the A/G ratio also had positive correlations with systolic blood pressure (BP) values (r = 0.273), triglycerides (r = 0.367), and 10-year ASCVD risk (r = 0.277). After adjusting for smoking, hypertension treatment, and type 2 diabetes, the 10-year ASCVD risk became significantly different for women in the first 5 years (3.28%) compared to those in years 5-10 of MP (3.74%), p = 0.047. Conclusions: In women with similar age and BMI, the A/G ratio appears to vary based on the number of years since menopause onset and correlates with either independent cardiovascular risk parameters like BP, triglycerides, and HDL cholesterol or with composite scores, such as 10-year ASCVD risk.

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PURPOSE OF REVIEW: The risk of incident atherosclerotic cardiovascular disease (ASCVD) in primary prevention is typically lower than in secondary prevention. However, there is a spectrum of risk among individuals undergoing primary prevention with the risk in some individuals approaching those of secondary prevention. We review the clinical conditions wherein the risk in primary prevention is similar to that observed in secondary prevention. RECENT FINDINGS: Among individuals without established ASCVD, coronary artery calcium (CAC) scores ≥ 300 AU are associated with ASCVD event rates similar to secondary prevention populations. CAC score ≥ 1,000 AU are associated with an ASCVD risk seen in very high-risk secondary prevention populations. Interpretation of these observations must however consider differences in the risk reduction strategies. Current guidelines dichotomize ASCVD prevention into primary and secondary prevention, but certain primary prevention patients have an ASCVD risk equivalent to that of secondary prevention populations. Identifying higher risk primary prevention populations will allow for better risk mitigation strategies.

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Recent trends indicate a concerning increase in early-onset atherosclerotic cardiovascular disease (ASCVD) among younger individuals (age < 55 in men and <65 in women). These findings highlight the pathobiology of ASCVD as a disease process that begins early in life and underscores the need for more tailored screening methods and preventive strategies. Increasing attention has been placed on the growing burden of traditional cardiometabolic risk factors in young individuals while also recognizing unique factors that mediate risk of premature atherosclerosis in this demographic such as substance use, socioeconomic disparities, adverse pregnancy outcomes, and chronic inflammatory states that contribute to the increasing incidence of early ASCVD. Additionally, mounting evidence has pointed out significant disparities in the diagnosis and management of early ASCVD and cardiovascular outcomes based on sex and race. Moving toward a more personalized approach, emerging data and technological developments using diverse tools such as polygenic risk scores and coronary artery calcium scans have shown potential in earlier detection of ASCVD risk. Thus, we review current evidence on causal risk factors that drive the increase in early ASCVD and highlight emerging tools to improve ASCVD risk assessment in young individuals.

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Significant advances in atherosclerotic cardiovascular (ASCVD) risk stratification and treatment have occurred over the past 10 years. While the lipid panel continues to be the basis of risk estimation, imaging for coronary artery calcium is now widely used in estimating risk at the individual level. Statins remain first-line agents for ASCVD risk reduction but in high-risk patients, ezetimibe, proprotein convertase subtilisin kexin-9 inhibitors, and bempedoic acid can be added to further reduce individual cardiovascular risk based on results of cardiovascular outcomes trials. Results of randomized control trials do not support use of medications targeted at triglyceride lowering for ASCVD risk reduction, but icosapent ethyl can be considered.

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Elevated low-density lipoprotein cholesterol (LDL-C) is a major causal factor for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide. Statins are the recommended first-line lipid-lowering therapy (LLT) for patients with primary hypercholesterolemia and established ASCVD, with LLT intensification recommended in the substantial proportion of patients who do not achieve levels below guideline-recommended LDL-C thresholds with statin treatment alone. The proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody evolocumab has demonstrated significant LDL-C reductions of > 60% in the clinical trial and open-label extension settings, with LDL-C reductions observed early post-evolocumab initiation and maintained long term, during up to 8.4 years of follow-up. Evolocumab therapy, when added to a statin, also conferred a significant reduction in major cardiovascular (CV) events, including a 20% reduction in the composite of CV death, myocardial infarction (MI), or stroke. The absolute benefits were enhanced among various patient types at high and very high risk for secondary ASCVD (e.g., with recent MI, multiple events or peripheral artery disease). Importantly, evolocumab treatment resulted in incremental CV risk reductions during the extended follow-up, including a 23% reduction in CV mortality and no apparent LDL-C level below which there is no further CV risk reduction. Hence, the evolocumab clinical data support the need for early and significant LDL-C lowering, especially in vulnerable ASCVD patients, in order to derive the greatest benefit in the long term. Importantly, evolocumab had no impact on any treatment emergent adverse events apart from a small increase in local injection site reactions. A growing body of real-world evidence (RWE) for evolocumab in heterogeneous populations is consistent with the trial data, including robust LDL-C reductions below guideline-recommended thresholds, a favourable safety profile even at the lowest levels of LDL-C achieved, and a high treatment persistence rate of > 90%. Altogether, this review highlights findings from 50 clinical trials and RWE studies in > 51,000 patients treated with evolocumab, to demonstrate the potential of evolocumab to address the healthcare gap in LDL-C reduction and secondary prevention of ASCVD in a variety of high- and very high-risk patients.