scholarly journals The Future of Lipid-lowering Therapy

2019 ◽  
Vol 8 (7) ◽  
pp. 1085 ◽  
Author(s):  
Zwol ◽  
Rimbert ◽  
Kuivenhoven
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Omega 3 ◽  
Therapeutic Modalities ◽  
Experimental Drugs ◽  
Apolipoprotein C ◽  
New Findings

The recent introduction of inhibitors of proprotein convertase subtilisin/kexin 9 to lower low-density lipoprotein (LDL) cholesterol on top of statins or as monotherapy is rapidly changing the landscape of treatment of atherosclerotic cardiovascular disease (ASCVD). However, existing lipid-lowering drugs have little impact on lipoprotein(a) (Lp(a)) or plasma triglycerides, two other risk factors for ASCVD. This review summarizes the evidence and the rationale to target Lp(a) and triglycerides and provides an overview of currently tested strategies to lower Lp(a), apolipoprotein C-III and angiopoietin-like protein 3. In addition, it summarizes new findings on the use of omega-3 fatty acids (OM3FA) to fight ASCVD. With the exception of OM3FA supplementation, the promise of the experimental drugs discussed here depends on the long-term safety and efficacy of monoclonal antibodies and/or antisense oligonucleotides Clinical outcome trials will ultimately prove whether these new therapeutic modalities will reduce ASCVD risk.

scholarly journals Lipid-Lowering Therapy in Patients with Coronary Heart Disease and Prior Stroke: Mission Impossible?

2021 ◽  
Vol 10 (4) ◽  
pp. 886
Author(s):  
Pier Luigi Temporelli ◽  
Marcello Arca ◽  
Laura D’Erasmo ◽  
Raffaele De Caterina
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Lipid Guidelines ◽  
Coronary Events

Hyperlipidemia is a powerful risk factor for coronary heart disease (CHD). It has been known for a long time that lipid-lowering drugs significantly reduce morbidity from CHD, thus proving a causal role for cholesterol in coronary events. Conversely, the relationship between low-density lipoprotein cholesterol (LDL-C) levels and stroke has been less clear and debated for many years. Recent data conclusively demonstrate not only the inverse epidemiological relationship of blood LDL-C with stroke, but also the efficacy of different strategies to attain cholesterol-lowering on stroke. They also dissipate lingering doubts about the possibility that lipid-lowering is linked to an increase in hemorrhagic stroke. However, despite current international lipid guidelines now strongly recommend aggressive lipid-lowering therapy in patients with atherosclerotic cardiovascular disease, including CHD and cerebrovascular disease (CeVD), secondary prevention patients are often undertreated with lipid-lowering therapies in routine clinical practice. This review highlights that patients with CHD and concomitant CeVD do not receive aggressive lipid-lowering therapy despite being at very high risk and with clear evidence of benefit from lowering LDL-C levels below current targets.

scholarly journals What Do US Physicians and Patients Think About Lipid‐Lowering Therapy and Goals of Treatment? Results From the GOULD Registry

2021 ◽  
Author(s):  
Suzanne V. Arnold ◽  
Christopher P. Cannon ◽  
James A. de Lemos ◽  
Robert S. Rosenson ◽  
Christie M. Ballantyne ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Shared Decision ◽  
Low Density Lipoprotein Cholesterol ◽  
Lowering Therapy

Background Because of an increasing number and complexity of treatment options for lipid‐lowering therapy in patients with atherosclerotic cardiovascular disease, guidelines recommend greater active involvement of patients in shared decision‐making. However, patients' understanding and perceptions of the benefits, risks, and treatment objectives of lipid‐lowering therapy are unknown. Methods and Results Structured questionnaires were conducted in 5006 US outpatients with atherosclerotic cardiovascular disease and suboptimal low‐density lipoprotein cholesterol (LDL‐C) control (LDL‐C ≥70 mg/dL) or on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor and in 113 physician providers as a part of the GOULD (Getting to an Improved Understanding of Low‐Density Lipoprotein Cholesterol and Dyslipidemia Management) Registry. Mean age of the patients was 68±10 years, 60% were men, and 86% were White race. Across all patients, 63% believed heart disease was the leading cause of death in men and 46% the leading cause of death in women. Only 28% of patients thought the primary reason they were taking lipid‐lowering medication was to lower the risk of heart attack or stroke, 68% did not know their approximate LDL‐C level, and 69% did not know their LDL‐C goal. Patients on PCSK9 inhibitors (versus LDL‐C cohort), younger patients (versus age ≥65 years), and men (versus women) were somewhat more knowledgeable about their disease and its management. Most physicians (66%) felt that a lack of understanding of the importance and efficacy of statins was the primary factor contributing to nonadherence, as opposed to costs (9%) or side effects (1%). More education was the most commonly used strategy to address patient‐reported side effects. Conclusions A large proportion of patients with atherosclerotic cardiovascular disease remain unaware of their underlying atherosclerotic cardiovascular disease risk, reasons for taking lipid‐lowering medications, current LDL‐C levels, or treatment goals. These data highlight a large education gap which, if addressed, may improve shared decision‐making and treatment adherence. Registration URL: https://www.clinicaltrials.org ; Unique identifier: NCT02993120.

Abstract 15913: Two-year Results of the Getting to an Improved Understanding of Low-density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) Registry of Patients With Atherosclerotic Cardiovascular Disease (ASCVD)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Christopher P Cannon ◽  
James A De Lemos ◽  
Christie M Ballantyne ◽  
Robert S Rosenson ◽  
Shushama Alam ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Treatment Guidelines ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitor ◽  
Statin Dose

Background: Atherosclerotic cardiovascular disease (ASCVD) treatment guidelines recommend intensive statin therapy and adding non-statin therapy if LDL-C ≥70 mg/dL. Methods: We designed the GOULD registry to assess lipid-lowering therapy (LLT) over time: At 120 U.S. centers, 5006 ASCVD patients on any (LLT) were enrolled in 1 of 3 cohorts: 1) currently on PCSK9 inhibitor (PCSK9i), 2) no PCSK9i and LDL-C ≥100 mg/dL, and 3) no PCSK9i and LDL-C 70-99 mg/dL. Results: Over the two years, only 16.8% had some type of LLT intensification, In the cohorts of patients with baseline LDL-C ≥ 100 and 70-99 mg/dL, LLT intensification was present in 21.9% and 14.3% respectively: statin dose was intensified in 6.1% and 6.1%, ezetimibe was added in 6.8% and 4.3% and PCSK9i was added in 6.3% and 2.2% respectively. Conversely, out of the total population, statins were discontinued in 246/4275 (5.8%), ezetimibe in 81/535 (15.1%), and PCSK9i in 47/544 (8.6%). At 24 months, 83.7% were on statin (43.4% high-intensity), with 14.2% on ezetimibe. Lipid panels were measured in 73% by 1 year and 84% by 2 years. Among Pts in the LDL-C ≥100 and 70-99 mg/dL cohorts, 18.6% and 30.4% achieved an LDL-C <70 mg/dL by 1 year, with little further change by 2 years: 21.3% and 33.5% respectively. In the PCSK9 cohort, 53.2% had LDL-C<70 mg/dl. Overall, only 31.7% had LDL-C <70 mg/dL at 2 years (an increase from 6.7% at baseline), while 25.0% had LDL-C >100 mg/dL. Conclusion: Of ASCVD patients with suboptimal LDL-C at baseline, even after 2 years of follow up, strikingly only 16% had LLT intensification, and thus most remained uncontrolled. Further intensive efforts are needed to achieve optimal LDL management in patients with ASCVD.

scholarly journals Escalation of liPid-lOwering therapy in patientS wiTh vascular disease receiving HIGH-intensity statins: the retrospective POST-HIGH study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jaehyung Ha ◽  
Bom Lee ◽  
Jung Mi Park ◽  
Moonjong Kang ◽  
Jaewon Oh ◽  
...  
Keyword(s):  
High Intensity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Control Group ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Kaplan Meier ◽  
Clinical Benefits

AbstractIn this retrospective study, we investigated whether lipid-lowering therapy (LLT) escalation has clinical benefits in patients with atherosclerotic cardiovascular disease (ASCVD) and low-density lipoprotein cholesterol (LDL-C) levels of 55–99 mg/dL (1.4–2.6 mmol/L), post high-intensity. Out of 6317 Korean patients screened in 2005–2018, 1159 individuals with ASCVD and LDL-C levels of 55–99 mg/dL after statin use equivalent to 40 mg atorvastatin were included. After 1:2 propensity score matching, 492 patients (164 with LLT escalation, 328 controls without LLT escalation) were finally analysed. Primary outcome variables were major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause death. At median follow-up (1.93 years), the escalation group had a lower MACCE rate (1.72 vs. 3.38 events/100 person-years; hazard ratio [HR] 0.34, 95% confidence interval [CI] 0.14–0.83; p = 0.018) than the control group. The incidence of all-cause death (0.86 vs. 1.02 events/100 person-years; HR 0.58, 95% CI 0.15–2.19; p = 0.42) and each MACCE component did not differ between groups. Kaplan–Meier curves exhibited lower risk of MACCE in the escalation group (HR 0.36, 95% CI 0.12–0.97; p = 0.040) but a difference not statistically significant in all-cause death (HR 0.30, 95% CI 0.04–2.48; p = 0.26). LLT escalation was associated with reduced cardiovascular risk, supporting more aggressive LLT in this population.

scholarly journals Clinical review on triglycerides

2019 ◽  
Vol 41 (1) ◽  
pp. 99-109c ◽  
Author(s):  
Ulrich Laufs ◽  
Klaus G Parhofer ◽  
Henry N Ginsberg ◽  
Robert A Hegele
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Clinical Problem ◽  
Primary Treatment ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Omega 3 ◽  
Omega 3 Fatty Acid ◽  
Emerging Therapies ◽  
Diet And Lifestyle

Abstract Hypertriglyceridaemia is a common clinical problem. Epidemiologic and genetic studies have established that triglyceride-rich lipoproteins (TRL) and their remnants as important contributors to ASCVD while severe hypertriglyceridaemia raises risk of pancreatitis. While low-density lipoprotein is the primary treatment target for lipid lowering therapy, secondary targets that reflect the contribution of TRL such as apoB and non-HDL-C are recommended in the current guidelines. Reduction of severely elevated triglycerides is important to avert or reduce the risk of pancreatitis. Here we discuss interventions for hypertriglyceridaemia, including diet and lifestyle, established treatments such as fibrates and omega-3 fatty acid preparations and emerging therapies, including various biological agents.

Structure and Function of Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in Hyperlipidemia and Atherosclerosis

2019 ◽  
Vol 20 (10) ◽  
pp. 1029-1040 ◽  
Author(s):  
Xinjie Lu
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Structure And Function ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Proprotein Convertase ◽  
Novel Target ◽  
New Treatments ◽  
And Function

Background:One of the important factors in Low-Density Lipoprotein (LDL) metabolism is the LDL receptor (LDLR) by its capacity to bind and subsequently clear cholesterol derived from LDL (LDL-C) in the circulation. Proprotein Convertase Subtilisin-like Kexin type 9 (PCSK9) is a newly discovered serine protease that destroys LDLR in the liver and thereby controls the levels of LDL in plasma. Inhibition of PCSK9-mediated degradation of LDLR has, therefore, become a novel target for lipid-lowering therapy.Methods:We review the current understanding of the structure and function of PCSK9 as well as its implications for the treatment of hyperlipidemia and atherosclerosis.Results:New treatments such as monoclonal antibodies against PCSK9 may be useful agents to lower plasma levels of LDL and hence prevent atherosclerosis.Conclusion:PCSK9's mechanism of action is not yet fully clarified. However, treatments that target PCSK9 have shown striking early efficacy and promise to improve the lives of countless patients with hyperlipidemia and atherosclerosis.

Efficacy and Safety of Evolocumab in Reducing Low Density Lipoprotein Cholesterol Levels in Chinese Patients with Non-ST-segment Elevation Acute Coronary Syndrome

2020 ◽  
Vol 18 ◽  
Author(s):  
Xiaohan Xu ◽  
Meng Chai ◽  
Yujing Cheng ◽  
Pingan Peng ◽  
Xiaoli Liu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Chinese Patients ◽  
Lipid Lowering ◽  
Control Group ◽  
Lipid Lowering Therapy ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
St Segment

Aims: To explore early intensive lipid-lowering therapy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels can reduce cardiovascular morbidity and mortality in patients with atherosclerotic cardiovascular disease. Due to many reasons, the need for early intensive lipid-lowering therapy is far from being met in Chinese NSTE-ACS patients at high-risk of recurrent ischaemic events. Objective: To evaluate the feasibility, safety and efficacy of starting evolocumab in hospital to lower LDL-C levels in Chinese patients with NSTE-ACS. Methods: In this prospective cohort study initiated by researchers, 334 consecutive patients with NSTE-ACS who had sub-standard LDL-C levels (LDL-C ≥2.3 mmol/L after regular oral statin treatment for at least 4 weeks; or LDL-C ≥3.2 mmol/L without regular oral statin treatment) were included. Patients who agreed to treatment with evolocumab (140 mg subcutaneously every 2 weeks, initiated in hospital and used for 12 weeks after discharge) were enrolled in the evolocumab group (n=96) and others in the control group (n=238). All enrolled patients received regular statin treatment (atorvastatin 20 mg/day or rosuvastatin 10 mg/day; doses unchanged throughout the study).The primary endpoint was the change in LDL-C levels from baseline to week 12. Results: Most patients (67.1%) had not received regular statin treatment before. In the evolocumab group, LDL-C levels decreased significantly at week 4 and remained stable at week 8 and 12 (all p<0.001). At week 12, the LDL-C percentage change from baseline in the evolocumab group was -79.2±12.7% (from an average of 3.7 to 0.7 mmol/L), while in the control group it was -37.4±15.4% (from an average of 3.3 to 2.0 mmol/L). The mean difference between these 2 groups was -41.8% (95% CI -45.0 to -38.5%; p<0.001). At week 12, the proportions of patients with LDL-C levels <1.8 mmol/L and 1.4 mmol/L in the evolocumab group were significantly higher than in the control group (96.8 vs 36.1%; 90.6 vs 7.1%; both p<0.001). The incidence of adverse events and cardiovascular events was similar in both groups. Conclusions: In this prospective cohort study we evaluated the early initiation of evolocumab in NSTE-ACS patients in China. Evolocumab combined with statins significantly lowered LDL-C levels and increased the probability of achieving recommended LDL-C levels, with satisfactory safety and well tolerance.

Abstract P560: Delipid Extracorporeal Lipoprotein Filter System: A New Lipid-Lowering Therapy for Acute Ischemic Stroke Patients

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Yuqiong Jiao ◽  
Ting Ye ◽  
Xiang Han
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasma Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Adsorption System ◽  
Stroke Patients ◽  
Safety Parameters

Objectives: The purpose of this study was to illustrate a new low-density lipoprotein cholesterol (LDL-C) adsorption system, Delipid Extracorporeal Lipoprotein filter from Plasma (DELP) system, and evaluate its safety and efficacy in acute ischemic stroke patients. Methods: This is an observational study of 22 acute ischemic stroke patients who underwent DELP treatment from March to August 2019. The DELP system was composed of a plasma filter JX-DELP, a COM.TEC cell separator and Tubing P1R Plasma Treatment Set. Clinical data and laboratory results including plasma lipids and some safety parameters before and after the apheresis were collected and analyzed. Results: The present study included 22 patients (15 males, 7 females, 59.95±13.71 years). The mean LDL-C was significantly reduced from 3.36±0.64 mmol/L to 2.30±0.53 mmol/L (31.5%, p <0.001, n=22) during a single DELP treatment, and from 3.59±0.48 mmol/L to 1.85±0.50 mmol/L (48.2%, p <0.001, n=13) after two apheresis, respectively. No clinically relevant changes were observed in hematologic safety parameters during DELP treatments. Conclusions: We concluded that the new LDL-C adsorption system is a promising method for timely and controllable LDL-C administration in acute ischemic stroke patients in view of its high efficacy, simple operation, and safety.

scholarly journals U-Shaped Relationship of Low-Density Lipoprotein Cholesterol With Risk of Severe COVID-19 From a Multicenter Pooled Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiao Gong ◽  
Yaqiong Chen ◽  
Yusheng Jie ◽  
Mingkai Tan ◽  
Zhaofang Jiang ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Odds Ratios ◽  
Lowering Therapy ◽  
Severe Group

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group (n = 460) and the severe group (severe and critical cases) (n = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12–4.68; p = 0.023) and 2.02 (1.04–3.94; p = 0.039), respectively, compared to those with LDL-C of 2.81–3.40 mmol/L (108.6–131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07–6.37; p = 0.035) and 2.36 (1.09–5.14; p = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.

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