scholarly journals New players in the treatment of hypercholesterolaemia: focus on bempedoic acid and inclisiran

2021 ◽  
Vol 23 (Supplement_E) ◽  
pp. E59-E62
Author(s):  
Massimiliano Ruscica ◽  
Cesare Riccardo Sirtori ◽  
Nicola Ferri ◽  
Alberto Corsini
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Oral Drug ◽  
Atherosclerotic Cardiovascular Disease ◽  
Atherosclerotic Burden ◽  
Risk Patients ◽  
Ascvd Risk ◽  
Coa Reductase ◽  
Interfering Rna ◽  
Hydroxymethylglutaryl Coa Reductase

Abstract Dyslipidaemias and in particular elevated plasma low-density lipoprotein cholesterol (LDL-C) levels are major risk factors for atherosclerotic cardiovascular disease (ASCVD). Indeed, the more LDL-C is reduced the larger will be the ASCVD risk reduction. Although statins represent the first-line intervention to reduce the atherosclerotic burden driven by raised levels of LDL-C, adherence is not optimal and most patients do not follow guidelines and recommended doses. Thus, to achieve optimal LDL-C goals, especially in very high-risk patients, there is a need for new and safe agents, more tolerable than statins with low risk of myalgia. Thus, the present review will address the most recent clinical trials with bempedoic acid and inclisiran. Bempedoic acid is an oral drug acting at a biochemical step preceding hydroxymethylglutaryl-CoA reductase and not associated with muscular side effects. Inclisiran, the first-in-class small interfering RNA-based approach, has the ability to effectively reduce LDL-C by inhibiting the hepatic synthesis of proprotein convertase subtilisin/kexin type 9, with the advantage of requiring subcutaneous of a single dose on Day 1, Day 90, and every 6 months thereafter.

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

New Approaches for the Prevention and Treatment of Cardiovascular Disease: Focus on Lipoproteins and Inflammation

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Aliza Hussain ◽  
Christie M. Ballantyne
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Annual Review ◽  
Publication Date ◽  
Atherosclerotic Cardiovascular Disease ◽  
Substantial Progress ◽  
Ascvd Risk ◽  
Made In

Although numerous trials have convincingly shown benefits of statin therapy in both primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), most showed relative risk reductions of 25–40%, and thus many individuals continue to have ASCVD events despite statin therapy. Substantial progress has been made in developing therapies that address the residual risk for ASCVD despite statin therapy. In this review, we summarize progress of currently available therapies along with therapies under development that further reduce low-density lipoprotein cholesterol and apolipoprotein B–containing lipoproteins, reduce lipoprotein(a), reduce ASCVD events in patients with high triglycerides, and directly target inflammation to reduce ASCVD risk. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Residual Cardiovascular Risk at Low LDL: Remnants, Lipoprotein(a), and Inflammation

2020 ◽  
Author(s):  
Ron C Hoogeveen ◽  
Christie M Ballantyne
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Residual Risk ◽  
Atherosclerotic Cardiovascular Disease ◽  
C Reactive Protein ◽  
Residual Cardiovascular Risk ◽  
Lipoprotein A ◽  
Reactive Protein ◽  
Increased Risk ◽  
Ascvd Risk

Abstract Background Current guidelines target low-density lipoprotein cholesterol (LDL-C) concentrations to reduce atherosclerotic cardiovascular disease (ASCVD) risk, and yet clinical trials demonstrate persistent residual ASCVD risk despite aggressive LDL-C lowering. Content Non–LDL-C lipid parameters, most notably triglycerides, triglyceride-rich lipoproteins (TGRLs), and lipoprotein(a), and C-reactive protein as a measure of inflammation are increasingly recognized as associated with residual risk after LDL-C lowering. Eicosapentaenoic acid in statin-treated patients with high triglycerides reduced both triglycerides and ASCVD events. Reducing TGRLs is believed to have beneficial effects on inflammation and atherosclerosis. High lipoprotein(a) concentrations increase ASCVD risk even in individuals with LDL-C &lt; 70 mg/dL. Although statins do not generally lower lipoprotein(a), proprotein convertase subtilisin/kexin type 9 inhibitors reduce lipoprotein(a) and cardiovascular outcomes, and newer approaches are in development. Persistent increases in C-reactive protein after intensive lipid therapy have been consistently associated with increased risk for ASCVD events. Summary We review the evidence that biochemical assays to measure TGRLs, lipoprotein(a), and C-reactive protein are associated with residual risk in patients treated to low concentrations of LDL-C. Growing evidence supports a causal role for TGRLs, lipoprotein(a), and inflammation in ASCVD; novel therapies that target TGRLs, lipoprotein(a), and inflammation are in development to reduce residual ASCVD risk.

scholarly journals A New Equation Based on the Standard Lipid Panel for Calculating Small Dense Low-Density Lipoprotein-Cholesterol and Its Use as a Risk-Enhancer Test

2021 ◽  
Author(s):  
Maureen Sampson ◽  
Anna Wolska ◽  
Russell Warnick ◽  
Diego Lucero ◽  
Alan T Remaley
Keyword(s):  
Survival Curve ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Least Squares Regression ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipid Panel ◽  
Ascvd Risk

Abstract Background Increased small dense low-density lipoprotein-cholesterol (sdLDL-C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD) but typically requires advanced lipid testing. We describe two new equations, first one for calculating large buoyant LDL-C (lbLDL-C), based only upon results from the standard lipid panel, and the second one for sdLDL-C. Methods Equations for sdLDL-C and lbLDL-C were generated with least-squares regression analysis using the direct Denka sdLDL-C assay as reference (n = 20 171). sdLDL-C was assessed as a risk-enhancer test in the National Heart and Nutrition Examination Survey (NHANES), and for its association with ASCVD in the Multi-Ethnic Study of Atherosclerosis (MESA). Results The newly derived equations depend on two terms, namely LDL-C as determined by the Sampson equation, and an interaction term between LDL-C and the natural log of triglycerides (TG). The lbLDL-C equation (lbLDLC=1.43 × LDLC-0.14 ×(ln⁡(TG)× LDLC)- 8.99) was more accurate (R2 = 0.933, slope = 0.94) than the sdLDL-C equation (sdLDLC=LDLC- lbLDLC; R2 = 0.745, slope = 0.73). Using the 80th percentile (46 mg/dL) as a cut-point, sdLDL-C identified in NHANES additional high-risk patients not identified by other risk-enhancer tests based on TG, LDL-C, apolipoprotein B, and nonHDL-C. By univariate survival-curve analysis, estimated sdLDL-C was superior to other risk-enhancer tests in predicting ASCVD events in MESA. After multivariate adjustment for other known ASCVD risk factors, estimated sdLDL-C had the strongest association with ASCVD compared to other lipid parameters, including measured sdLDL-C. Conclusions Estimated sdLDL-C could potentially be calculated on all patients tested with a standard lipid panel to improve ASCVD risk stratification.

scholarly journals 337. Switching from TDF to TAF: Missed Opportunities for Statin Use in HIV

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S179-S179
Author(s):  
Patrick Mallon ◽  
Laurence Brunet ◽  
Jennifer S Fusco ◽  
Girish Prajapati ◽  
Andrew P Beyer ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Low Density Lipoprotein ◽  
Healthcare Providers ◽  
Density Lipoprotein ◽  
People Living With Hiv ◽  
Atherosclerotic Cardiovascular Disease ◽  
Missed Opportunities ◽  
Ascvd Risk ◽  
Missed Opportunity

Abstract Background People living with HIV (PLWH) have been observed to have twice the risk for atherosclerotic cardiovascular disease (ASCVD) as the general population. Increases in total and low-density lipoprotein cholesterol have been observed in PLWH switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Changes in regimens represent an opportunity for healthcare providers to assess health markers and address clinical concerns. Current guidelines recommend initiating statin therapy in individuals with an elevated ASCVD risk. Failure to initiate statins in PLWH with an ASCVD ≥ 7.5% at switch represents a missed opportunity for statin initiation. We aimed to assess missed opportunities for statin therapy in PLWH switching from TDF to TAF-containing antiretroviral therapy. Methods Adults switching from TDF to TAF with ≥1 lipid measure on TDF ≤6 months prior to switch and ≥1 lipid measure ≥7 days after switch to TAF were identified in the OPERA® cohort (84 clinics in 18 US states/territories). The proportion of PLWH prescribed statins pre- and post-switch was stratified by ASCVD risk (recommended threshold: ASCVD ≥ 7.5%). The ASCVD score was imputed using the limit value for components out of the pre-specified range. Results 6,451 PLWH switched from TDF to TAF (Figure 1); over 90% had ASCVD scores available pre- (n = 5801) and post-switch (n = 5881). High ASCVD risk (≥7.5%) was more likely post-switch (34.1) than pre-switch (32.1%, P = 0.02; Figure 2). Of those with high ASCVD risk, only 31% and 41% were prescribed statins pre- vs. post-switch, respectively (Figure 3), representing a considerable missed opportunity for ASCVD prevention, with 59% of PLWH with an elevated risk of ASCVD not prescribed statins after switch from TDF to TAF. ASCVD scores were imputed for those outside the range of the score (e.g., patients < 40 years of age) to evaluate the entire population. Comparable results were obtained when the analysis was limited to PLWH who did not require ASCVD score imputation. Conclusion Despite a switch from TDF to TAF being associated with higher numbers of PLWH with elevated ASCVD risk, most did not receive a statin, representing considerable missed opportunities to reduce risk of cardiovascular disease in this at-risk population. Disclosures All authors: No reported disclosures.

Abstract 14845: Remnant Cholesterol and Incident Atherosclerotic Cardiovascular Disease: A Pooled Cohort Primary Prevention Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Renato Quispe ◽  
Seth S Martin ◽  
Erin D Michos ◽  
Isha Lamba ◽  
Roger S Blumenthal ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Primary Prevention ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Atherosclerotic Cardiovascular Disease ◽  
Prognostic Information ◽  
Cox Models ◽  
Remnant Cholesterol ◽  
Ascvd Risk

Introduction: Emerging evidence suggests that remnant cholesterol (RC) promotes future atherosclerotic cardiovascular disease (ASCVD) events. Our aim was to estimate the risk associated with RC beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). Hypothesis: RC provides incremental prognostic information regarding incident ASCVD, independent of LDL-C and apoB. Methods: We pooled data from 17,532 individuals from Atherosclerosis Risk in Communities study (n=9,748), Multi-Ethnic Study of Atherosclerosis (n=3,049) and Coronary Artery Risk Development in Young Adults (n=4,735), who were ASCVD-free at baseline and had measurements of lipids, apoB and apolipoprotein A1. RC was calculated as non-high-density cholesterol (non-HDL-C) minus LDL-C estimated by the Martin/Hopkins equation. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in discordant/concordant groups of RC and LDL-C across median cutpoints and cutpoints of percentile equivalence to LDL-C targets (70 and 100 mg/dL). Results: Mean age of participants was 52.3±17.9 years, 56.7% women and 34% black. There were 2,143 ASCVD events over median follow-up of 18.7 years. After multivariable adjustment including apoB and HDL-C, logRC was associated with higher ASCVD risk [HR 1.42, 95% CI (1.23-1.63)]. In discordance analyses, the high RC and low LDL-C group (≥/<median) was associated with increased ASCVD risk compared to the low/low concordant group [1.17, (1.01-1.35)] but the low RC and high LDL-C group was not. Similar results were shown when examining discordance across lower cutpoints. Conclusion: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors and LDL-C and apoB levels. RC assessment and management in primary prevention, beyond LDL-C and apoB, is useful and requires further scrutiny.

LDL-cholesterol lowering efficacy of atorvastatin® in primary prevention. Real-world experience in a developing country; a program based on evidence, personalization, and empowerment

2021 ◽  
Vol 9 (11) ◽  
Author(s):  
Enrique Morales-Villegas ◽  
Abigail Vega-Velasco ◽  
Gualberto Moreno-Virgen
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Prevention ◽  
Scientific Quality ◽  
Atherosclerotic Cardiovascular Disease ◽  
Net Benefit ◽  
Therapeutic Class ◽  
Risk Patients

Despite the iconoclasts of the LDL-centric principle and the net benefit of statins, the plurality, quantity, and especially the scientific quality of the evidence that supports the causal role of low-density lipoprotein cholesterol (LDL-C) in atherosclerosis, as well as the net benefit of statins in its prevention, make these two concepts, universal principles accepted by all guidelines worldwide. The efficacy, safety, and cost-effectiveness of statins have been confirmed in multiple randomized and controlled clinical trials. However, paradoxically, and especially in developing countries like Mexico, the use of this therapeutic class is suboptimal. The reasons to explain this paradox are multiple and are analyzed in this article, which has the purpose of confirming the efficacy, safety, and significant potential impact of statins in the "real developing world." To fulfill this purpose, this article presents our center experience using statins, especially atorvastatin®, in patients without atherosclerotic cardiovascular disease (ASCVD). Founded on an evidence-based, personalization, and empowerment program, our results in almost four hundred patients in primary cardiovascular prevention are as follows. In intermediate-risk patients, atorvastatin® 10 mg/day with a baseline LDL-C of 111.6 mg/dL (±25.1), reduced LDL-C by 38.0% (±13.9); atorvastatin® 20 mg/day with a baseline LDL-C of 124.4 mg/dL (±25.3), reduced LDL-C by 44.9% (±15.0) (p <0.005 for both). In the atorvastatin® 10/20 mg/day cohort (a total of 294 patients), 87.7% (258 patients) achieved a ≥30% LDL-C reduction, and 36.7% (108 patients) a ≥50% reduction. In the atorvastatin 10/20 mg/day cohort, with an average baseline LDL-C of 122.6 mg/dL (±25.6), 92.5 and 55.7% achieved LDL-C of ≤100 and ≤70 mg/dL, respectively. In high-risk patients, atorvastatin® 40 mg/day with a baseline LDL-C of 151.7 mg/dL (±31.6), there was an LDL-C average reduction of 54.7% (±12.2). Atorvastatin 80mg/day with a baseline LDL-C of 160.2 mg/dL (±41.5) produced an LDL-C average reduction of 62.5% (±10.8) (P <0.005 for both). In the atorvastatin® 40/80 mg/day cohort (89 patients), 98.8% (88 patients) achieved a ≥30% LDL-C reduction, and 76.4% (68 patients) achieved a ≥50% reduction. In the atorvastatin 40/80 mg/day cohort, with an average baseline LDL-C of 153.0 mg/dL (±33.2), 95.8 and 62.9% achieved LDL-C of ≤100 and ≤70 mg/dL, respectively.

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