scholarly journals Simulation of the Impact of Statin Intolerance on the Need for Ezetimibe and/or Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor for Meeting Low-Density Lipoprotein Cholesterol Goals in a Population With Atherosclerotic Cardiovascular Disease

2019 ◽  
Vol 123 (8) ◽  
pp. 1202-1207 ◽  
Author(s):  
Christopher P. Cannon ◽  
Robert J. Sanchez ◽  
Alexa C. Klimchak ◽  
Irfan Khan ◽  
William J. Sasiela ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Proprotein Convertase ◽  
Low Density Lipoprotein Cholesterol ◽  
Statin Intolerance ◽  
The Impact

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines

2020 ◽  
pp. 204748732094010
Author(s):  
Konstantinos C Koskinas ◽  
Baris Gencer ◽  
David Nanchen ◽  
Mattia Branca ◽  
David Carballo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Coronary Syndromes

Aims The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes. Methods and results We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria. Conclusions In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

Abstract P181: Atherogenic Lipoproteins and Incident Atherosclerotic Cardiovascular Disease in the Framingham Offspring Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Hiroaki Ikezaki ◽  
Elise Lim ◽  
Ching-Ti Liu ◽  
L Adrienne Cupples ◽  
Bela F Asztalos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Significant Information ◽  
Ascvd Risk

Introduction: Elevated plasma low-density lipoprotein cholesterol (LDL-C), small-dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), triglycerides (TG), remnant-lipoprotein cholesterol (RLP-C), triglyceride-rich lipoprotein-C (TRL-C), very low-density lipoprotein cholesterol (VLDL-C), and lipoprotein(a) [Lp(a)] levels have been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, these parameters have not been included in risk factors for ASCVD in the pooled cohort equation (PCE). Hypothesis: We assessed the hypothesis that these atherogenic lipoprotein parameters add significant information for ASCVD risk prediction in the Framingham Offspring Study. Methods: We evaluated 3,147 subjects without ASCVD at baseline (mean age 58 years) from participants of Framingham Offspring Study cycle 6, 677 (21.5%) of whom developed inclusive ASCVD over 16 years. Biomarkers of risk were assessed in frozen plasma samples. Total cholesterol, TG, HDL-C, direct LDL-C, sdLDL-C, LDL-TG, Lp(a), RLP-C, and TRL-C were measured by standardized automated analysis. Calculated LDL-C, large buoyant low-density lipoprotein cholesterol (lbLDL-C), VLDL-C, and non-HDL-C values were calculated. Data were analyzed using Cox proportional regression analysis and net reclassification improvement (NRI) analysis to identify parameters significantly associated with the incidence of ASCVD after controlling for standard ASCVD risk factor and applying the PCE model. Results: All specialized lipoprotein parameters were significant ASCVD risk factors on univariate analysis, but only direct LDL-C, sdLDL-C, and Lp(a) were significant on multivariate analysis with standard risk factors in the model. Together these parameters significantly improved the model c statistic (0.716 vs 0.732, P < 0.05) and net risk reclassification (mean NRI 0.104, P < 0.01) for ASCVD risk. Using the ASCVD risk pooled cohort equation, sdLDL-C, TG, LDL-TG, LDL-C, RLP-C, and TRL-C individually added significant information, but no other parameter added significant information with sdLDL-C (hazard ratio 1.30 for 75th vs 25th percentile, P < 0.0001) in the model. Conclusions: In multivariate analysis, sdLDL-C, direct LDL-C, and Lp(a) contributed significantly to ASCVD risk, but only sdLDL-C added significant risk information to the PCE model, indicating that sdLDL-C may be the most atherogenic lipoprotein particle.

CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE ALGORITHM – 2020 EXECUTIVE SUMMARY

2020 ◽  
Vol 26 (10) ◽  
pp. 1196-1224 ◽  
Author(s):  
Yehuda Handelsman ◽  
Paul S. Jellinger ◽  
Chris K. Guerin ◽  
Zachary T. Bloomgarden ◽  
Eliot A. Brinton ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Icosapent Ethyl ◽  
Lipid Disorders ◽  
Ascvd Risk

The treatment of lipid disorders begins with lifestyle therapy to improve nutrition, physical activity, weight, and other factors that affect lipids. Secondary causes of lipid disorders should be addressed, and pharmacologic therapy initiated based on a patient’s risk for atherosclerotic cardiovascular disease (ASCVD). Patients at extreme ASCVD risk should be treated with high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol (LDL-C) of <55 mg/dL, and those at very high ASCVD risk should be treated to achieve LDL-C <70 mg/dL. Treatment for moderate and high ASCVD risk patients may begin with a moderate-intensity statin to achieve an LDL-C <100 mg/dL, while the LDL-C goal is <130 mg/dL for those at low risk. In all cases, treatment should be intensified, including the addition of other LDL-C-lowering agents (i.e., proprotein convertase subtilisin/kexin type 9 inhibitors, ezetimibe, colesevelam, or bempedoic acid) as needed to achieve treatment goals. When targeting triglyceride levels, the desirable goal is <150 mg/dL. Statin therapy should be combined with a fibrate, prescription-grade omega-3 fatty acid, and/or niacin to reduce triglycerides in all patients with triglycerides ≥500 mg/dL, and icosapent ethyl should be added to a statin in any patient with established ASCVD or diabetes with ≥2 ASCVD risk factors and triglycerides between 135 and 499 mg/dL to prevent ASCVD events. Management of additional risk factors such as elevated lipoprotein(a) and statin intolerance is also described. Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; ACS = acute coronary syndrome; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BA = bempedoic acid; CAC = coronary artery calcium; CHD = coronary heart disease; CK = creatine kinase; CKD = chronic kidney disease; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; FCS = familial chylomicronemia syndrome; FDA = United States Food and Drug Administration; FOURIER = Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; HDL-C = high-density lipoprotein cholesterol; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hyper-cholesterolemia; hsCRP = high-sensitivity C reactive protein; IDL = intermediate-density lipoproteins; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; IPE = icosapent ethyl; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein a; MACE = major adverse cardiovascular events; MI = myocardial infarction; OSA = obstructive sleep apnea; PCSK9 = proprotein convertase subtilisin/kexin type 9; REDUCE-IT = Reduction of Cardiovascular Events with EPA-Intervention Trial; UKPDS = United Kingdom Prospective Diabetes Study; U.S. = United States; VLDL = very-low-density lipoproteins

scholarly journals Low‐Density Lipoprotein Cholesterol Corrected for Lipoprotein(a) Cholesterol, Risk Thresholds, and Cardiovascular Events

2020 ◽  
Vol 9 (23) ◽  
Author(s):  
Peter Willeit ◽  
Calvin Yeang ◽  
Patrick M. Moriarty ◽  
Lena Tschiderer ◽  
Stephen A. Varvel ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Care ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein A ◽  
The Impact

Background Conventional "low‐density lipoprotein cholesterol (LDL‐C)" assays measure cholesterol content in both low‐density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of “LDL‐C” and corrected LDL‐C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline‐recommended LDL‐C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from “LDL‐C” to obtain corrected LDL‐C values (LDL‐C corr30 ). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual‐patient‐data meta‐analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow‐up). When comparing top versus bottom quartiles, the multivariable‐adjusted hazard ratio for cardiovascular disease was significant for “LDL‐C” (1.17; 95% CI, 1.05–1.31; P =0.005) but not for LDL‐C corr30 (1.07; 95% CI, 0.93–1.22; P =0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline‐recommended LDL‐C categories when using LDL‐C corr30 was assessed. In “LDL‐C” categories of 70 to <100, 100 to <130, 130 to <190, and ≥190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL‐C categories when LDL‐C corr30 was used: 30.2% (30.0%–30.4%), 35.1% (34.9%–35.4%), 32.9% (32.6%–33.1%), and 41.1% (40.0%–42.2%), respectively. Conclusions “ LDL‐C” was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL‐C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.

scholarly journals Low-density lipoprotein cholesterol lowering therapy for the secondary prevention of atherosclerotic cardiovascular disease

2020 ◽  
Vol 2020 (3) ◽  
Author(s):  
Parth N Patel ◽  
Robert P Giugliano
Keyword(s):  
Cardiovascular Disease ◽  
Secondary Prevention ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Blood Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lowering Therapy

Atherosclerotic cardiovascular disease (ASCVD) is highly prevalent and a major contributor to morbidity and mortality worldwide. Elevated blood cholesterol is a key driver of risk for atherosclerotic events, and patients with established ASCVD comprise a specific high-risk population in which low-density lipoprotein cholesterol (LDL-C) lowering therapy is strongly endorsed by multiple guidelines. An increasing number of medications across several pharmacologic classes are available today in clinical practice. Therefore, guidance on the appropriate use of these interventions is necessary for cost-effective solutions to managing residual atherothrombotic risk. In this review we summarize the key evidence supporting LDL-C lowering as described in the most recent 2018 multi-society Blood Cholesterol Guidelines, and provide a framework for optimizing LDL-C lowering therapy in secondary prevention populations.

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