scholarly journals Real-world risk of cardiovascular outcomes associated with hypertriglyceridaemia among individuals with atherosclerotic cardiovascular disease and potential eligibility for emerging therapies

2019 ◽  
Author(s):  
Patrick R Lawler ◽  
Gynter Kotrri ◽  
Maria Koh ◽  
Shaun G Goodman ◽  
Michael E Farkouh ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Real World ◽  
Coronary Revascularization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Death ◽  
Atherosclerotic Cardiovascular Disease ◽  
Icosapent Ethyl ◽  
Emerging Therapies ◽  
Event Rates

Abstract Aims Hypertriglyceridaemia in patients with atherosclerotic cardiovascular disease (ASCVD) has been in focus following the REDUCE-IT trial showing benefit with icosapent ethyl. Among individuals with prevalent ASCVD, we sought to quantify the contemporary, real-world risk of ASCVD events associated with hypertriglyceridaemia, as well as estimate icosapent ethyl eligibility and compare trial participants with REDUCE-IT-like individuals in the population. Methods and results We examined data from 2 424 865 adults with lipid panels in the Ontario population. Among those with prevalent ASCVD, we examined adjusted associations between triglyceride (TG) and ASCVD events (first occurrence of myocardial infarction, unstable angina, stroke or transient ischaemic attack, coronary revascularization, or cardiovascular death). The proportion of patients with ASCVD potentially eligible for icosapent ethyl was estimated as those with TG 135–499 mg/dL (1.52–5.63 mmol/L) and low-density lipoprotein cholesterol (LDLc) 41–100 mg/dL (1.06–2.59 mmol/L), similar to the lipid cut-offs in REDUCE-IT, and their demographics and event rates examined. Among 196 717 individuals with ASCVD, median age was 69 years and 30% were female. A total of 24 097 composite ASCVD events occurred over a mean (standard deviation) 2.9 (0.5) years of follow-up. Increasing TG was associated with a graded, progressively higher hazard of ASCVD events. Twenty-five percent (49 886) of individuals with ASCVD had hypertriglyceridaemia and controlled LDLc; these patients were demographically similar to those in REDUCE-IT with comparable event rates. Conclusions Among patients with ASCVD, hypertriglyceridaemia is common, and is associated with higher ASCVD risk across a range of TG. It is possible that as many as one in four patients with ASCVD may be candidates for emerging therapies.

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 Real-world use of PCSK9 inhibitors: A single-center experience

2018 ◽  
Vol 47 (1) ◽  
pp. 265-270 ◽  
Author(s):  
Sinan Sarsam ◽  
Abeer Berry ◽  
George Degheim ◽  
Robby Singh ◽  
Marcel Zughaib
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Profile ◽  
Real World ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
The Impact

Objective Hyperlipidemia is an important risk factor for atherosclerotic cardiovascular disease. Many patients are intolerant to or have limited benefit from statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved for treating hyperlipidemia in these patients. We sought to investigate the impact of these medications in a real-world cardiology practice. Methods This was a retrospective study of 17 patients with either heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol (LDL-C) levels above the treatment target despite maximally tolerated statins. Baseline lipid profile was compared with a repeat lipid profile obtained 4 to 6 weeks after initiating treatment with a PCSK9 inhibitor. Results The average duration of PCSK9 inhibitor treatment was 10.7 months. Lipid profile comparison showed that total cholesterol decreased from 243 ± 72 to 148 ± 39 (mg/dL) (39% reduction), triglycerides decreased from 185 ± 86 to 149 ± 62 (mg/dL) (19.5% reduction), high-density lipoprotein cholesterol increased from 56 ± 20 to 62 ± 26 (mg/dL) (10.7% increase), and LDL-C decreased from 154 ± 30 to 57 ± 32 (mg/dL) (63% reduction) from baseline. Conclusions PCSK9 inhibitors as add-on therapy to maximally tolerated statins resulted in an approximately 63% reduction in LDL-C.

scholarly journals Profound reductions in first and total cardiovascular events with icosapent ethyl in the REDUCE-IT trial: why these results usher in a new era in dyslipidaemia therapeutics

2019 ◽  
Vol 41 (24) ◽  
pp. 2304-2312 ◽  
Author(s):  
William E Boden ◽  
Deepak L Bhatt ◽  
Peter P Toth ◽  
Kausik K Ray ◽  
M John Chapman ◽  
...  
Keyword(s):  
Eicosapentaenoic Acid ◽  
Statin Therapy ◽  
Primary Endpoint ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Death ◽  
Atherosclerotic Cardiovascular Disease ◽  
Omega 3 ◽  
Icosapent Ethyl ◽  
Lipid Phenotype

Abstract The aims of this clinical review are to: (i) highlight the importance of elevated baseline triglycerides (TG) in the setting of well-controlled low-density lipoprotein cholesterol (LDL-C) on statins as a major contributor to residual atherosclerotic cardiovascular disease (ASCVD) risk, particularly among patients with type 2 diabetes mellitus, metabolic syndrome, and obesity whose distinctive lipid phenotype cannot be optimally treated with LDL-C reduction therapy alone; (ii) describe the findings and clinical implications of the landmark REDUCE-IT trial in which ethyl eicosapentaenoic acid significantly improved ASCVD outcomes. While many genetic studies have shown that elevated TG are an independent causal factor for ASCVD, prior placebo-controlled trials using niacin, fibrates, omega-3 fatty acids, and dietary supplement fish oil preparations have failed to demonstrate significant CV event reduction when added to statin therapy. In contrast, the REDUCE-IT trial in 8179 participants showed convincingly that the administration of 4 g daily of icosapent ethyl (an ethyl ester of eicosapentaenoic acid) in patients at high risk for ASCVD with increased levels of baseline TG [median value, 2.44 mmol/L (216.0 mg/dL)] but well-controlled LDL-C [median value, 1.94 mmol/L (75.0 mg/dL)] reduced significantly incident events across both the trial primary endpoint and multiple prespecified secondary endpoints, including cardiovascular death, as well as both subsequent and total primary endpoint and key secondary endpoint events. Icosapent ethyl unequivocally contributed to ASCVD event reduction over and above statin therapy. The REDUCE-IT trial results should alter our approach to managing a growing population of hypertriglyceridaemic patients whose lipid phenotype requires more intensive treatment beyond LDL-C lowering alone.

Low-density lipoprotein cholesterol goal attainment and treatment patterns in a cohort of >143,000 patients with atherosclerotic cardiovascular disease in Ontario, Canada

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fairbairn ◽  
P Oh ◽  
R Goeree ◽  
R.M Rogoza ◽  
M Packalen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Goal Attainment ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Data Repository ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Abstract Background/Introduction Limited real-world data are available on attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Canada. Purpose A retrospective observational study was conducted to describe types of ASCVD events/procedures, time between events and use of lipid lowering treatment (LLT) in patients who did not achieve LDL-C goal. Methods Patients in Ontario ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1-year follow up period for LDL-C goal attainment (&lt;2.0 mmol/L or 50% reduction from index LDL-C) and analysed by LLT and by index event type. Results Overall, 28% of 143,302 patients ≥65 years on LLT failed to attain LDL-C goal at follow up (Figure). The proportion of patients failing to achieve LDL-C goal decreased from 35% to 22% over the 11-year study period. Mean time between index and follow up LDL-C (based on lowest score &gt;2 weeks and up to 1 year after index LDL-C) was 203±97 days. When analysed by low-, moderate- or high-intensity statin, 57%, 30%, and 22% of patients failed to achieve LDL-C goal at follow up, respectively. Conclusions In this study, more than 1 in 4 patients with ASCVD in Ontario failed to achieve guideline recommended LDL-C goal despite treatment. In particular, ∼1 in 3 patients with cerebral and peripheral arterial disease were not at goal. An opportunity exists to better manage these high risk ASCVD patients with further statin intensification and additional LLTs This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc.

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.

scholarly journals Focus on… Praluent®

2020 ◽  
pp. 175-178
Author(s):  
L Steyn
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pivotal Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein Receptors

Cholesterol plays a pivotal role in the functioning of healthy cells. Being mostly lipophilic, cholesterol is transported in the blood inside lipophilic particles, e.g. high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Hypercholesterolaemia refers to elevated low-density lipoprotein cholesterol (LDL-C) levels, and increases the risk for premature atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein receptors (LDL-R) on the surface of hepatocytes, are the primary receptors involved in clearing circulating LDL-C.

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.

Dyslipidaemia

2019 ◽  
pp. 33-48
Author(s):  
Heinz Drexel
Keyword(s):  
Cardiovascular Disease ◽  
Randomized Clinical Trials ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Epidemiological Studies ◽  
Residual Risk ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cholesterol Levels

Lipid metabolism has gained cardiological interest only after statins were demonstrated to reduce cardiovascular disease in secondary and primary prevention. Therefore, this chapter first introduces the physiological and atherogenic properties of lipoproteins, before focusing on interventions. Both the efficacy and safety of statins have been proven in numerous randomized clinical trials. Because there is a considerable residual risk in statin-treated patients, additional approaches have been investigated. The focus is now on further reductions in low-density lipoprotein (LDL) cholesterol levels. First, high-intensity statin regimens were shown to reduce residual risk. Subsequently, ezetimibe was demonstrated, for the first time, to have a beneficial effect as a non-statin lipid intervention. More recently, inhibitors of the enzyme PCSK9 have demonstrated a very high efficacy in reducing LDL cholesterol levels. Although the causality of LDL for atherosclerotic cardiovascular disease has been proven in epidemiological studies, including Mendelian randomization studies, as well as interventional trials, adherence to statins and other therapies is far from optimal. In contrast, interventions to increase high-density lipoprotein (HDL) cholesterol levels could not proven to have further benefits when combined with statins.

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