Cholesterol

Despite the development of new therapies to lower cardiovascular disease (CVD) risk in recent decades, the trend of reductions in CVD mortality has reversed. New therapies are essential for the prevention of first and recurrent CVD. The importance of lowering low-density lipoprotein cholesterol (LDL-C) in the management and prevention of atherosclerotic CVD (ASCVD) is widely reflected in clinical treatment guidelines; however, most patients with established ASCVD do not achieve guideline-recommended LDL-C targets...

Elevated low density lipoprotein (LDL) cholesterol and lipoprotein(a) (Lp(a)) levels have an important role in the development and progression of atherosclerosis, followed by cardiovascular events. Besides statins and other lipid-modifying drugs, PCSK9 monoclonal antibodies are known to reduce hyperlipidemia. PCSK9 monoclonal antibodies decrease LDL cholesterol levels through inducing the upregulation of the LDL receptors and moderately decrease Lp(a) levels. In addition, PCSK9 monoclonal antibodies have shown non-lipid effects...

The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such as the antisense oligonucleotides and small interfering RNAs (siRNAs) that operate upstream, blocking the mRNA translation of the proteins specifically involved in lipid metabolism. In this review, we briefly explain the mechanisms of action of these molecules and discuss the difficulties related to their in vivo use as therapeutical agents...

Background: Patients with diabetes have an increased risk of developing vulnerable plaques (VPs), in which dyslipidemia and chronic inflammation play important roles. Non-high-density lipoprotein cholesterol (non-HDL-C) and neutrophil-lymphocyte ratio (NLR) have emerged as potential markers of both coronary artery VPs and cardiovascular prognosis. This study aimed to investigate the predictive value of non-HDL-C and NLR for coronary artery VPs in patients with type 2 diabetes mellitus (T2DM)...

BACKGROUND: REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) reported a 25% relative risk reduction in major adverse cardiovascular events with use of icosapent ethyl compared with pharmaceutical grade mineral oil. The mechanisms underlying this benefit remain uncertain. We explored whether treatment allocation in REDUCE-IT might affect a series of biomarkers in pathways known to associate with atherosclerosis risk. METHODS: Serum levels of interleukin-1β, interleukin-6, high-sensitivity C-reactive protein, oxidized low-density lipoprotein cholesterol, homocysteine, lipoprotein(a), and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured at baseline, at 12 months, at 24 months, and at the end-of-study visit among REDUCE-IT participants with triglyceride levels ≥ 135 mg/dL and <500 mg/dL who were randomly allocated to treatment with either 4 grams daily of icosapent ethyl or mineral oil used as a comparator...

BACKGROUND: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. METHODS: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy...

Metabolic risk for cardiovascular and other systems includes much more than just LDL cholesterol. This JCL Roundtable brings together 3 experts to address new opportunities to reduce the risks posed by obesity, diabetes, and fatty liver disease. Successful nutritional approaches to weight loss are diverse and need to be matched with individual preferences. Topiramate plus extended-release phentermine has been shown to promote meaningful weight loss in randomized trials, but the patented drug combination is expensive...

Background: Genetic loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis. Methods: Adults with non-high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks)...

BACKGROUND: Nearly 40% of patients do not continue proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) therapy after 6 months, despite their ability to lower low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular events. Limited work has assessed persistence to PCSK9i therapy in an integrated specialty pharmacy model. OBJECTIVE: To assess rates of persistence to PCSK9i therapy and report reasons for non-persistence in patients serviced within an integrated specialty pharmacy...

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse. OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins. METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort)...

Statins are lipid-lowing medications shown to reduce cardiovascular events and are recommended for specific patient populations at elevated risk of atherosclerotic cardiovascular disease (ASCVD). Despite the demonstrated efficacy of statins for reducing ASCVD risk, and guidance on which populations should receive statin therapy, a substantial portion of eligible patients are not prescribed statin therapy. Pharmacists have attempted to increase the number of eligible patients receiving appropriate statin therapy through a variety of interventions and across several clinical settings...

Clinical lipidology practice works best when implemented by a health care team. The 3 discussants for this JCL Roundtable are National Lipid Association leaders representing essential areas on the team - Registered Dietitian Nutritionist, Advanced Practice Provider, and Clinical Pharmacist. The team approach has been shown more effective than traditional sole provider management for controlling chronic asymptomatic conditions like hypercholesterolemia. Teams also fit better as health care transitions away from fee-for-service into value-based reimbursement...

BACKGROUND: Inclisiran, a small interfering RNA molecule, reduces low-density lipoprotein cholesterol (LDL-C) by inhibiting production of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the liver. OBJECTIVE: To investigate the pharmacokinetics, pharmacodynamics, and safety of inclisiran in patients with mild or moderate hepatic impairment (HI) vs participants with normal hepatic function (NHF). METHODS: In this single-center, open-label, parallel-group study, patients with mild (Child-Pugh A) or moderate (Child-Pugh B) HI and with NHF, matched by age, body mass index, sex, and race (if possible), received a single subcutaneous therapeutic dose of inclisiran (300 mg)...

Evidence suggests that caffeine (CF) reduces cardiovascular disease (CVD) risk. However, the mechanism by which this occurs has not yet been uncovered. Here, we investigated the effect of CF on the expression of two bona fide regulators of circulating low-density lipoprotein cholesterol (LDLc) levels; the proprotein convertase subtilisin/kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR). Following the observation that CF reduced circulating PCSK9 levels and increased hepatic LDLR expression, additional CF-derived analogs with increased potency for PCSK9 inhibition compared to CF itself were developed...

BACKGROUND: Lipid management for prevention and treatment of cardiovascular disease remains insufficient for many with currently available therapies. OBJECTIVE: Evaluate real-world use of bempedoic acid. METHODS: Retrospective study of patients in our Center for Preventive Cardiology who were prescribed bempedoic acid between February 2020 and July 2021. Patients were managed according to clinical standards of care, with lipid assessments at months ≤3, 6, and 12 post-bempedoic acid initiation...

AIM: To evaluate the effect of bempedoic acid on glycaemic and lipid variables in patients with hypercholesterolaemia. METHODS: A patient-level pooled analysis of four phase 3, randomized, double-blind, placebo-controlled trials evaluated changes in glycaemia, change from baseline in LDL-C, and adverse events. Patients (N = 3621) on maximally tolerated statins were randomized 2:1 to oral bempedoic acid 180 mg or placebo once daily for 12 to 52 weeks with the results analysed by baseline glycaemic status (diabetes, prediabetes, or normoglycaemia)...

Low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for the development of atherosclerotic cardiovascular disease. Statins have been the gold standard for managing cholesterol levels and reducing the risks associated with atherosclerotic cardiovascular disease; however, many patients do not achieve their cholesterol goals or are unable to tolerate this drug class due to adverse drug events. Recent studies of non-statin cholesterol lowering drugs (i.e., ezetimibe, PCSK9 inhibitors) have demonstrated cardiovascular benefits; and new drugs [i...

PURPOSE: Evaluate associations between outpatient low-density lipoprotein cholesterol (LDL-C) testing and subsequent statin adherence and intensification in patients after an atherosclerotic cardiovascular (ASCVD) event. METHODS: Longitudinal study of adult members of Kaiser Permanente Northern California hospitalized with an ASCVD event (myocardial infarction or stroke) during 01/01/2016 to 12/31/2017 with follow-up through 12/31/2019. Outcomes were statin adherence (estimated using continuous medication gap (CMG)) and intensification (defined by an increased dose or switch to a higher-intensity statin) based on pharmacy dispensing...

BACKGROUND: The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up. METHODS: We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline...

The value of primary preventative therapies for cardiovascular disease (CVD) in older adults (age ≥75 years) is less certain than in younger patients. There is a lack of quality evidence in older adults due to underenrolment in pivotal trials. While aspirin is no longer recommended for routine use in primary prevention of CVD in older adults, statins may be efficacious. However, it is unclear which patient subgroups may benefit most, and guidelines differ between expert panels. Three relevant geriatric conditions (cognitive impairment, functional impairment and polypharmacy) may influence therapeutic decision making; for example, baseline frailty may affect statin efficacy, and some have advocated for deprescription in this scenario...