AIM The “2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia” retires and replaces the “2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol.” METHODS A comprehensive literature search was conducted from October 2024 to December 2024 to identify clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE The focus of this clinical practice guideline is to address the evaluation, management, and monitoring of individuals with dyslipidemias, including high blood cholesterol, hypertriglyceridemia, and elevated lipoprotein(a).

BACKGROUND:Reducing LDL cholesterol prevents atherosclerotic cardiovascular disease (ASCVD) events. The aim of this study was to evaluate the LDL cholesterol-lowering efficacy of a fixed-dose combination (FDC) of obicetrapib, a CETP inhibitor, and ezetimibe. METHODS:This randomised, double-blind trial across 48 US sites including hospitals, private and group practices, and independent research centres included participants at least 18 years old with pre-existing or high risk for ASVCD or heterozygous familial hypercholesterolaemia with LDL cholesterol concentrations of 1·8 mmol/L (70 mg/dL) or greater despite maximally tolerated lipid-lowering therapy excluding ezetimibe, or having statin intolerance. Participants were randomly assigned (1:1:1:1) to obicetrapib 10 mg plus ezetimibe 10 mg FDC, obicetrapib 10 mg monotherapy, ezetimibe 10 mg monotherapy, or placebo administered daily for 84 days. The co-primary endpoints in the intention-to-treat population were the percent LDL cholesterol changes in the FDC group compared with placebo, ezetimibe monotherapy, and obicetrapib monotherapy, and the placebo-adjusted change in the obicetrapib monotherapy group. The trial was prospectively registered (NCT06005597) and is completed. FINDINGS:Between March 4 and July 3, 2024, 407 participants were randomly assigned. The median age was 68·0 years (IQR 62·0-73·0) and 177 (43%) were female. Mean baseline LDL cholesterol was 2·4 mmol/L, 2·5 mmol/L, 2·6 mmol/L, and 2·5 mmol/L in the placebo (n=102), ezetimibe monotherapy (n=101), obicetrapib monotherapy (n=102), and FDC groups (n=102), respectively. At day 84, percent differences in LDL cholesterol reduction with the FDC were -48·6% (95% CI -58·3 to -38·9) versus placebo, -27·9% (-37·5 to -18·4) versus ezetimibe, and -16·8% (-26·4 to -7·1) versus obicetrapib. Obicetrapib monotherapy decreased LDL cholesterol by 31·9% (22·1 to 41·6) versus placebo. Adverse event rates were similar in the FDC (52 [51%] of 102), obicetrapib (55 [54%] of 102), and ezetimibe (54 [53%] of 101) groups and lowest with placebo (38 [37%] of 102). Serious adverse event rates were generally similar across FDC (three [3%] of 102), obicetrapib (six [6%] of 102), ezetimibe (seven [7%] of 101), and placebo (four [4%] of 102) groups. Deaths occurred in one [1%] of 102 participants with FDC, one [1%] of 102 with obicetrapib, one [1%] of 101 with ezetimibe, and none with placebo. INTERPRETATION:Combination therapy of obicetrapib and ezetimibe significantly reduced LDL cholesterol. This oral, single-pill therapy could improve LDL cholesterol management in patients with pre-existing or high risk for ASCVD. FUNDING:NewAmsterdam Pharma.

Abstract Disclosure: R.J. Shah: None. A.C. Goldberg: None. S. Jasim: None. Introduction: Metastatic disease to the adrenal gland is the most commonly occurring malignancy of the adrenal glands. Adrenal hemorrhage (AH) however is a rare but potentially fatal manifestation of malignancy. This case report highlights the unusual presentation of retroperitoneal sarcoma, manifesting as bilateral adrenal hemorrhage in the context of underlying metastases. Case Presentation: A 53-year-old man presented with a 4-week history of fatigue, intermittent abdominal pain radiating to the back, and vomiting. CT revealed bilateral adrenal masses measuring up to 8.5cm on the left side, with Hounsfield units (HU) 27, and 5.9cm on the right, HU 27, consistent with large areas of bilateral adrenal hemorrhage later confirmed on MRI. Biochemical evaluation included ACTH-stimulated cortisol, which was borderline at 17.4mcg/dl (recommended above 18-20mcg/dl), with a significantly elevated ACTH level of 103.8pg/nl (reference range 7.0-63.0pg/ml). Plasma metanephrines, electrolytes, aldosterone, and DHEA-S were normal. Although hemodynamically stable, he was started on prednisone 5mg daily as he was at high risk for primary adrenal insufficiency (AI). He was referred to endocrine surgery and further workup with PET/CT demonstrated a new FDG-avid periaortic retroperitoneal mass, with an interval increase in the size of the adrenal masses and development of hypoattenuating lesions in the kidneys and pancreas favoring aggressive metastatic disease. He underwent biopsy of the retroperitoneal mass, and pathology was consistent with high-grade sarcoma. Oncology started treatment with dexrazoxane and doxorubicin. His adrenal masses remained unchanged in size, and the patient died related to rapid progression of disease. Discussion: Spontaneous bilateral adrenal hemorrhage is rare with a reported incidence of 0.14 to 1.8%. Although most cases have been associated with sepsis, anticoagulation, hematologic disorders and trauma, it is important to maintain a high level of suspicion for underlying adrenal tumors and metastatic disease. AH can be a diagnostic challenge because of its non-specific presentation, and imaging is vital for timely recognition. Patients with bilateral AH should be managed with corticosteroids to avert AI-related fatalities. Presentation: 6/1/2024

Introduction: Breast cancer (BC) is the most common non-cutaneous cancer in women. Several BC treatments increase the risk of conduction abnormalities and heart failure, potentially requiring cardiac implantable electrical devices (CIEDs). Due to vascular access devices, surgical management, and chest wall radiation, these patients are subject to upper extremity vascular alterations. There is limited data regarding CIED use in this population. Research question: Do patients with BC and CIEDs have different procedural approaches or complications compared to the general population? Aims: This study aimed to evaluate CIED placement and periprocedural complications in patients with a history of BC. Methods: This was a retrospective study of CIEDs placed at our institution between 2005 and 2023. Patients with a diagnosis of BC prior to time of placement were included. Complications included those within 30 days of the procedure. Results: We analyzed 109 female patients (median age of 73 years, IQR 66-80) who received pacemaker (PPM, 58.7%), cardiac resynchronization therapy defibrillator (CRT-D, 22%), implantable cardioverter defibrillator (ICD, 16.5%), or cardiac resynchronization therapy pacemaker (CRT-P, 2.8%). The median time from cancer diagnosis to device placement was 13 years (IQR 7-21). Oncologic therapies are included in Figure 1. In patients with unilateral cancer, most devices (78.4%) were placed contralaterally, with 32% of all devices being right sided. Anatomy related to chemotherapy port altered intraoperative approach in 2 cases and bilateral lymph node dissection necessitated subcutaneous ICD in 1 case. Complications were noted in 12 patients (11%) and included hematoma, lead revision, upper extremity DVT, pericardial effusion, stress cardiomyopathy, perforation, site infection, and worsening of chronic lymphedema. Conclusions: BC survivors undergoing CIED placement appear to be at higher risk of periprocedural complications when compared to the general population. They are more likely to undergo right sided device placement to avoid vascular access ipsilateral to prior surgery or radiation. Further studies are required to understand the long-term outcomes of CIED placement in this cohort of patients.

Background The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant variations in pre-analytical requirements, methods, nomenclature, and reporting work flows.Content The guidance document aims to improve standardization of clinical lipid testing work flows. It provides recommendations for the components of the lipid panel, fasting requirements, reporting of results, and specific recommendations for non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (apo B), point-of-care lipid testing, and LDL subfraction testing.Summary Lipid panels should always report non-HDL-C and LDL-C calculations if possible. Fasting is not routinely required except in specific cases. Modern equations should be utilized for LDL-C calculation. These equations allow for LDL-C reporting at elevated concentrations of triglycerides and obviate the need for direct measured LDL-C in most cases.

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) often cannot reach guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals despite multidrug therapy. Objective: To evaluate the efficacy and safety of bempedoic acid as an add-on therapy for lowering LDL-C in patients with HeFH. Methods: Pooled data from two 52-week phase 3 clinical trials of patients with atherosclerotic cardiovascular disease and/or HeFH receiving maximally tolerated statin therapy (randomized 2:1 to bempedoic acid or placebo) were analyzed by HeFH status. Endpoints included changes from baseline to week 12 (and up to week 52) in LDL-C and other lipid parameters, achievement of LDL-C goals, and safety. Results: A total of 217 (bempedoic acid, 146; placebo, 71) patients with HeFH and 2,792 (bempedoic acid, 1,864; placebo, 928) without HeFH were included (mean baseline LDL-C, 172.8 mg/dL and 102.6 mg/dL, respectively). Bempedoic acid significantly lowered LDL-C at week 12 vs. placebo regardless of HeFH status (with HeFH, -21.2%; without HeFH, -18.2% [both P<0.0001]). Bempedoic acid significantly reduced other lipid parameters and high-sensitivity C-reactive protein vs. placebo regardless of HeFH status (all P <= 0.01). Among patients with HeFH treated with bempedoic acid, 32% and 27% achieved LDL-C <100 mg/dL at weeks 12 and 52, respectively. Overall treatment-emergent adverse event incidence was comparable across all four groups (74.7-77.5%). Conclusion: Bempedoic acid significantly lowered LDL-C levels vs. placebo and was generally well tolerated in all patients, with no new safety findings in patients with HeFH, despite more intensive lipid-lowering therapy in patients with vs. without HeFH.

Background/Synopsis Obicetrapib, an orally delivered cholesteryl ester transfer protein inhibitor, reduces concentrations of atherogenic lipid parameters and increases HDL-C when added to statins. Objective/Purpose BROOKLYN examined the efficacy, safety, and tolerability of obicetrapib 10 mg, as an adjunct to maximally tolerated lipid-modifying therapies, in patients with heterozygous familial hypercholesterolemia (HeFH) and suboptimal LDL-C control. Methods This was a phase 3, randomized, double-blind, placebo-controlled trial NCT05425745 with 1 year follow up in 354 patients across 70 sites. Participants (n = 354) with HeFH and fasting LDL-C ³70 mg/dL taking maximally tolerated lipid-modifying therapies were randomly assigned to receive obicetrapib 10 mg or matching placebo orally daily for 52 weeks in a 2:1 ratio. Study primary endpoint assessed obicetrapib compared with placebo in LS mean percent change from baseline to week 12 in LDL-C. Secondary endpoints included obicetrapib compared with placebo in percent changes from baseline in Apo B, non-HDL-C, HDL-C, total-C, Lp(a), and TG, and safety measures; Apo A1 was an exploratory endpoint. Results Mean baseline lipoprotein lipid levels for obicetrapib and placebo, respectively, were LDL-C: 123.4 and 119.9 mg/dL; ApoB: 107.2 and 105.3 mg/dL; non-HDL-C: 148.4 and 146.7 mg/dL; and HDL-C: 53.2 and 50.2 mg/dL. Obicetrapib, compared with placebo, significantly reduced mean LDL-C -36.3% at day 84 (P < 0.0001) and -41.5% at day 365 (P < 0.0001). On day 84 and day 365, obicetrapib, compared with placebo, significantly reduced mean ApoB -24.4%, -25.8%; non-HDL-C -34.5%, -37.5%; Lp(a) -45.9%, -54.3%; and increased HDL-C 138.7%, 121.4%, respectively. Obicetrapib was well tolerated with no serious adverse events or clinically significant changes in vital signs, electrocardiograms, or other clinical laboratory values. Conclusions Obicetrapib, as an adjunct to maximally tolerated lipid-modifying therapies, produced significant LDL-C lowering at day 84 with sustained effect through day 365 in patients with HeFH. Obicetrapib holds promise for patients with HeFH who are unable to attain their LDL-C treatment targets with available lipid-lowering agents.Previously Published: American Heart Association (AHA) Scientific Sessions 2024:Circulation. 2024; 150: e712- e729 - e73

Background and aims: Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid.Methods: Patients were grouped into two pools: 1) atherosclerotic cardiovascular disease (ASCVD) and/or het-erozygous familial hypercholesterolemia (HeFH) "on statins" and 2) "low-dose or no statin". Percent changes from baseline to at least week 12 in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex.Results: Overall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acid vs. placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools (p <= 0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (-21.2% vs.-17.4%; p = 0.044), non-HDL-C (-17.3% vs.-12.1%; p = 0.003), TC (-13.8% vs.-10.5%; p = 0.012), and Apo B (-16.0% vs.-11.3%; p = 0.004) in the ASCVD and/or HeFH on statins pool. Women had similar reductions to men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was com-parable between sexes.Conclusions: In this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid.

Background and aims Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid.Methods Patients were grouped into two pools: atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) “on statins”, and “low-dose or no statin”. Percent changes from baseline to at least week 12 in low-density lipoprotein-cholesterol (LDL-C), non–high-density lipoprotein-cholesterol (non–HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex.Results Overall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acid vs . placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools ( p ≤0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (−21.2% vs . −17.4%; p =0.044), non–HDL-C (−17.3% vs . −12.1%; p =0.003), TC (−13.8% vs . −10.5%; p =0.012), and Apo B ( − 16.0% vs . −11.3%; p =0.004) in the ASCVD and/or HeFH on statins pool. Women had numerically greater reductions than men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was comparable between sexes.Conclusions In this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid.### Competing Interest StatementA.C.G. has received research grants/support from Amgen, Akcea/Ionis, Arrowhead, Esperion Therapeutics, Inc., NewAmsterdam Pharma, Novartis, Pfizer, Regeneron, and Sanofi; has served as a consultant for Akcea, Esperion Therapeutics, Inc., NewAmsterdam Pharma, IONIS, Novartis, and Regeneron, and performed editorial work for the Merck Manuals. M.B. has received research grants/support from Amgen, Sanofi, Mylan/Viatris, and Valeant, and has served as a consultant for Amgen, Daiichi Sankyo, Esperion Therapeutics, Inc., Freia Pharmaceutici, Herbapol, Kogen, KRKA, Novartis, Novo Nordisk, Polfarmex, Polpharma, Regeneron, Sanofi Aventis, Servier, Teva, and Zentiva; he serves as Chief Medical Officer at Nomi Biotech Corporation Ltd. A.L.C. has received research grants/support from Amarin, Amgen, Menarini, Mylan, Sanofi, and Sanofi Regeneron, and has served as a consultant for or received honoraria from Akcea, Amarin, Amgen, Daiichi Sankyo, Esperion Therapeutics, Inc., Ionis, Kowa, Medco, Menarini, MSD, Mylan, Novartis, Recordati, Regeneron, Sanofi, and The Corpus. P.B.D. has received institutional research grants/support from Regeneron, Regenxbio, and Retrophin/Travere, and has served as a consultant for Akcea, Esperion Therapeutics, Inc., Ionis, Kaneka, Regeneron, and Novo Nordisk. L.A.L. has received research grants/support from Amgen, AstraZeneca, Kowa, The Medicines Company, and Novartis. He has also served as an advisor and/or provided continuing medical education on behalf of Amarin, Amgen, AstraZeneca, Esperion Therapeutics, Inc., HLS, Merck, Novartis, Pfizer, and Sanofi. J.C.H. is an employee of Esperion Therapeutics, Inc. and may own Esperion stock or stock options. L.L. is a consultant contracted by Esperion Therapeutics, Inc. and may own Esperion stock or stock options. G.B.J.M. has received research grant(s)/support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, HLS Therapeutics, Merck, Novo Nordisk, and Sanofi, and has served as a consultant for these companies, as well as Esperion Therapeutics, Inc., Novartis, Amgen, Sanofi, and Servier. ### Funding StatementThis work was supported by Esperion Therapeutics, Inc. The work of ALC was supported in part by Ministero della Salute, Ricerca corrente.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:In all four trials (CLEAR Wisdom [[NCT02991118][1]], CLEAR Harmony [[NCT02666664][2]], CLEAR Tranquility [[NCT03001076][3]], and CLEAR Serenity [[NCT02988115][4]]) protocols were approved by local independent ethics committees at each study site, and all study participants provided written informed consent.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02991118&atom=%2Fmedrxiv%2Fearly%2F2023%2F02%2F15%2F2023.02.14.23285912.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02666664&atom=%2Fmedrxiv%2Fearly%2F2023%2F02%2F15%2F2023.02.14.23285912.atom [3]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03001076&atom=%2Fmedrxiv%2Fearly%2F2023%2F02%2F15%2F2023.02.14.23285912.atom [4]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02988115&atom=%2Fmedrxiv%2Fearly%2F2023%2F02%2F15%2F2023.02.14.23285912.atom

IntroductionFamilial hypercholesterolemia (FH) is a common inherited cholesterol disorder that, without early intervention, leads to premature cardiovascular disease. Multilevel strategies that target all components of FH care including identification, cascade testing, and management are needed to address gaps that exist in FH care. We utilized intervention mapping, a systematic implementation science approach, to identify and match strategies to existing barriers and develop programs to improve FH care.MethodsData were collected utilizing two methods: a scoping review of published literature, related to any component of FH care, and a parallel mixed method study using interviews and surveys. The scientific literature was searched using key words including “barriers” or “facilitators” and “familial hypercholesterolemia” from inception to December 1, 2021. The parallel mixed method study recruited individuals and families with FH to participate in either dyadic interviews (N = 11 dyads/22 individuals) or online surveys (N = 98 respondents). Data generated from the scoping review, dyadic interviews, and online surveys were used in the 6-step intervention mapping process. Steps 1–3 included a needs assessment, development of program outcomes and creation of evidence-based implementation strategies. Steps 4–6 included program development, implementation, and evaluation of implementation strategies.ResultsIn steps 1–3, a needs assessment found barriers to FH care included underdiagnosis of the condition which led to suboptimal management due to a myriad of determinants including knowledge gaps, negative attitudes, and risk misperceptions by individuals with FH and clinicians. Literature review highlighted barriers to FH care at the health system level, notably the relative lack of genetic testing resources and infrastructure needed to support FH diagnosis and treatment. Examples of strategies to overcome identified barriers included development of multidisciplinary care teams and educational programs. In steps 4–6, an NHLBI-funded study, the Collaborative Approach to Reach Everyone with FH (CARE-FH), deployed strategies that focused on improving identification of FH in primary care settings. The CARE-FH study is used as an example to describe program development, implementation, and evaluation techniques of implementation strategies.ConclusionThe development and deployment of evidence-based implementation strategies that address barriers to FH care are important next steps to improve identification, cascade testing, and management.

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). The primary endpoint for all studies was the percent change from baseline to week 12 in LDL-C levels. Safety and tolerability were assessed by laboratory values and adverse events. Results: In the Phase 3 No Statin Cohort, bempedoic acid (n = 394) lowered LDL-C levels at week 12 significantly more than placebo (n = 192; -26.5% [95% CI, -29.7%, -23.2%]; P < 0.001). The fixed-dose combination of bempedoic acid with ezetimibe lowered LDL-C by 39.2% (95% CI, -51.7% to -26.7%; P < 0.001). Muscle-related disorders occurred at a rate of 26.4 and 28.6 per 100 person-years with bempedoic acid and placebo, respectively. Conclusions: In patients with hypercholesterolemia unable to take statins, bempedoic acid lowered LDL-C levels by a mean of 26.5% vs placebo and bempedoic acid + ezetimibe fixed-dose combination lowered LDL-C by 39.2%. The treatments were generally well tolerated, suggesting that bempedoic acid may be efficacious and well tolerated in this challenging-to-treat patient population. (C) 2022 National Lipid Association. Published by Elsevier Inc.

Purpose of Review There have been recent developments of novel therapeutic agents for lipid lowering. This article reviews treatment concepts for two of the newest lipid-lowering medications. Recent Findings Bempedoic acid inhibits adenosine citrate lyase, decreasing intracellular lipogenesis. This oral medication is a prodrug and requires activation by enzymes present in hepatocytes but absent in the skeletal muscle. Clinical trials demonstrated additive benefit with statin therapy, and it was well tolerated in statin-intolerant populations. Inclisiran uses RNA interference to prevent translation of PCSK9 mRNA. Due to its stability, it can be given as an injection every 6 months and produces consistent, durable, and potent cholesterol lowering. Summary Bempedoic acid and inclisiran represent new avenues of treatment for the prevention and treatment of cardiovascular disease. This will allow for more comprehensive care by addressing challenges with medication adherence, such as adverse effects to prior medications as well as ease of dosing.

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality, and statins have become a cornerstone in its treatment and prevention. Despite the well-documented benefits of statins, many patients stop taking them, with adverse muscle symptoms being a commonly cited reason. Although some statin-associated adverse muscle effects are real, some can be attributed to the nocebo effect, which is the patient's perception of harm. The purpose of this article is to review the literature on statin safety, particularly that related to muscle, to analyze adverse effects, and to propose various treatment strategies for the statin intolerant patient.

Purpose of review: Cardiovascular disease is the leading cause of death in the United States with incidence expected to increase in the coming decades. Recent years have produced a variety of new and novel therapeutics aimed at reducing the global burden of cardiovascular disease. This review highlights these recent advancements. Recent findings: In addition to more rigorous therapeutic thresholds for traditional LDL lowering agents such as statins, recent studies have developed new pathways of lipid lowering for both typical cardiovascular disease and complex, genetic lipid disorders. This includes inhibition of the cholesterol synthesis enzyme ATP citrate lyase with bempedoic acid, prevention of PCSK9 mRNA translation with inclisiran, inhibition of the lipoprotein lipase inhibitor angiopoetin like 3 protein with evinacumab and the use of anti-sense oligonucleotides to lower lipoprotein(a) levels. Icosapent ethyl, while remaining a topic of debate and controversy, demonstrates efficacy in cardiovascular risk reduction when all available data are examined. Lastly fibrate therapy continues to produce negative results in terms of cardiovascular disease reduction. Summary: Recent years have yielded breadth and depth to cardiovascular treatments. This expanded armamentarium will allow for more effective and more consistent treatment and prevention of cardiovascular disease.(c) 2022 Elsevier Inc. All rights reserved.

BACKGROUND:Non-statin lipid lowering therapies (LLTs) provide additional treatment options for patients. Use patterns and patient perceptions of non-statin LLT remain incompletely described. HYPOTHESIS:The guideline-recommended statin intensity remains underutilized in patients treated with and without non-statin LLT. METHODS:The PALM Registry collected LLT information on patients with or at risk of ASCVD treated at 125 US clinics in 2015. We compared patient perceptions, lipid levels and statin use among patients treated with and without non-statin LLT. RESULTS:Among 7720 patients, 1930 (25.0%) were treated with a non-statin LLT (1249 fish oil, 417 fibrates, 329 ezetimibe, 196 niacin). Concurrent statin treatment occurred in 73.7%, of which 45.4% were dosed under the guideline-recommended intensity. Compared with patients on statin alone, patients receiving both a statin and non-statin LLT (n = 1423) were more likely to be male, white race and to perceive themselves as higher risk of ASCVD compared with their peers (38.5% vs. 34.9%, p = .047). Only 27.4% of patients treated with non-statin LLT alone perceived themselves at higher risk. Most (75.7%) patients treated with a non-statin LLT alone reported never being treated with a statin, despite ASCVD in 30.8% of these patients. Among those previously treated with a statin, 59.3% reported being willing to try a statin again. CONCLUSIONS:Non-statin LLT is used in one in four patients with or at risk for ASCVD; its use is frequently in place of statin therapy or in the absence of guideline-recommended statin intensity. More work is needed to establish statins as first line therapy.

This chapter provides an overview of the major types of fatty acids, including polyunsaturated, monounsaturated, and saturated fatty acids. It reviews the differences in structural and biochemical properties of these fatty acids to provide a foundation for understanding the metabolic effects of each. We describe plant-based oils that are composed primarily of polyunsaturated fatty acids (soybean, corn, and walnut oil), monounsaturated fatty acids (canola and rapeseed, sunflower and safflower, olive, and peanut oil), saturated fatty acids (palm and palm kernel and coconut oil), and trans-fatty acids (partially hydrogenated vegetable oil). Finally, we will examine and compare the effects of these different oils on metabolic and cardiovascular outcomes based on a comprehensive review of the current literature.

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low‐density‐lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US‐based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively; P=0.15). However, Black versus EA patients had significantly greater prevalence of modifiable risk factors, including body mass index (mean, 32±7 kg/m2 versus 29±6 kg/m2; P<0.001), hypertension (82% versus 50%; P<0.001), diabetes (39% versus 15%; P<0.001), and current smoking (16% versus 8%; P=0.006). Black versus EA patients also had significantly lower usage of statins (61% versus 73%; P=0.004) and other lipid‐lowering agents. In a fully adjusted multivariate model, race was not independently associated with ASCVD (odds ratio, 0.92; 95% CI, 0.60–1.49; P=0.72). Conclusions The strongest predictors of ASCVD in Black patients with familial hypercholesterolemia were hypertension and cigarette smoking. These data support wider usage of statins and other lipid‐lowering therapies and greater attention to modifiable risk, specifically blood pressure management and smoking cessation.

•Prevention of disease should be a central focus in healthcare and society.•Our society vastly underperforms when it comes to achieving optimal health metrics.•Society should encourage the integrating healthy habits into routine activities.

Purpose of Review Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in women across all racial and ethnic groups within the USA. Despite robust evidence from randomized controlled trials demonstrating that treatment of hypercholesterolemia in women reduces cardiovascular events, women who are eligible for lipid-lowering therapy are less likely than men to be prescribed guideline-recommended therapy or to have therapy prescribed at the appropriate intensity. Recent Findings Historically, women have been underrepresented in clinical trials. Recent randomized clinical trials have shown that women derive similar benefits as men when treated with lipid-lowering therapy, and recent studies demonstrate potential uses for lipid-lowering therapies that extend beyond their previously well-established indications. In this review, we will discuss lipid-lowering therapies in the context of recent clinical trials with a focus on special considerations in women.