Treating Coronary Artery Disease: Beyond Statins, Ezetimibe, and PCSK9 Inhibition

Musunuru, Kiran

doi:10.1146/annurev-med-080819-044918

Cited by 13 publications

(8 citation statements)

References 73 publications

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“… 9 Ezetimibe is a second-line agent, reducing the absorption of cholesterol by the gastrointestinal tract via inhibition of the Niemann-Pick C1-like 1 (NPC1L1) protein. 10 PCSK9 inhibitors is a new class of agents that is also a valuable addition to lipid-lowering therapy, blocking the lysosomal degradation of LDLR. When added to statin therapy, PCSK9 inhibitors cause LDL-C levels to plummet down by 60%.…”

Section: Introductionmentioning

confidence: 99%

Angiopoietin-Like Protein 3 (ANGPTL3) Inhibitors in the Management of Refractory Hypercholesterolemia

Kosmas¹,

Bousvarou²,

Sourlas³

et al. 2022

CPAA

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Cardiovascular disease (CVD) is the most common cause of death in a global scale and significantly depends on the elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and the subsequent formation of atherosclerotic plaques. While physicians have several LDL-C-lowering agents with diverse mechanisms of action, including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and inclisiran, angiopoietin-like protein 3 (ANGPTL3) inhibitors have recently emerged as a powerful addition in the armamentarium of lipid-lowering strategies, especially for patients with refractory hypercholesterolemia, as in the case of patients with homozygous familial hypercholesterolemia (HoFH). ANGPTL3 protein is a glycoprotein secreted by liver cells that is implicated in the metabolism of lipids along with other ANGPTL proteins. These proteins inhibit lipoprotein lipase (LPL) and endothelial lipase (EL) in tissues. Loss-of-function mutations affecting the gene encoding ANGPTL3 are linked with lower total cholesterol, LDL-C, and triglyceride (TG) levels. Evinacumab is a monoclonal antibody that targets, binds to, and pharmacologically inhibits ANGPTL3, which was recently approved by the United States Food and Drug Administration (FDA) as a complementary agent to other LDL-C lowering regimens for patients aged 12 or older with HoFH, based on clinical trial evidence that confirmed its safety and efficacy in those patients. Antisense oligonucleotides (ASOs) also represent an interesting class of agents that target and inhibit the mRNA derived from the transcription of ANGPTL3 gene. This review aims to present and discuss the current clinical and scientific data pertaining to the role of ANGPTL3 inhibitors, a novel lipid-modifying class of agents capable of reducing LDL-C levels via a mechanism independent of LDL receptors.

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Section: Introductionmentioning

confidence: 99%

Angiopoietin-Like Protein 3 (ANGPTL3) Inhibitors in the Management of Refractory Hypercholesterolemia

Kosmas¹,

Bousvarou²,

Sourlas³

et al. 2022

CPAA

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“…Clinical trials exploring the cardiovascular and renal outcomes of GLP-1RA and sodium-glucose cotransporter-2 inhibitors (SGLT2i) not only change the treatment paradigm of diabetes but also support a more holistic approach beyond glycemic control which emphasize on cardiac and reno-protective effects ( 36 ). Although statins, ezetimibe, and PCSK9 inhibitors are the standard of care for coronary artery disease, many novel LDL cholesterol–lowering drugs, such as inclisiran recently approved by the FDA, may transform the care of patients who are at risk of life-threatening coronary events ( 37 , 38 ). KDF is harmful but treatable if individuals at risk are identified at an early stage.…”

Section: Discussionmentioning

confidence: 99%

The temporal trend of disease burden attributable to metabolic risk factors in China, 1990–2019: An analysis of the Global Burden of Disease study

Jin

Cerin

et al. 2023

Front. Nutr.

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Background and aimsThe disease burden attributable to metabolic risk factors is rapidly increasing in China, especially in older people. The objective of this study was to (i) estimate the pattern and trend of six metabolic risk factors and attributable causes in China from 1990 to 2019, (ii) ascertain its association with societal development, and (iii) compare the disease burden among the Group of 20 (G20) countries.MethodsThe main outcome measures were disability-adjusted life-years (DALYs) and mortality (deaths) attributable to high fasting plasma glucose (HFPG), high systolic blood pressure (HSBP), high low-density lipoprotein (HLDL) cholesterol, high body-mass index (HBMI), kidney dysfunction (KDF), and low bone mineral density (LBMD). The average annual percent change (AAPC) between 1990 and 2019 was analyzed using Joinpoint regression.ResultsFor all six metabolic risk factors, the rate of DALYs and death increased with age, accelerating for individuals older than 60 and 70 for DALYs and death, respectively. The AAPC value in rate of DALYs and death were higher in male patients than in female patients across 20 age groups. A double-peak pattern was observed for AAPC in the rate of DALYs and death, peaking at age 20–49 and at age 70–95 plus. The age-standardized rate of DALYs increased for HBMI and LBMD, decreased for HFPG, HSBP, KDF, and remained stable for HLDL from 1990 to 2019. In terms of age-standardized rate of DALYs, there was an increasing trend of neoplasms and neurological disorders attributable to HFPG; diabetes and kidney diseases, neurological disorders, sense organ diseases, musculoskeletal disorders, neoplasms, cardiovascular diseases, digestive diseases to HBMI; unintentional injuries to LBMD; and musculoskeletal disorders to KDF. Among 19 countries of Group 20, in 2019, the age-standardized rate of DALYs and death were ranked fourth to sixth for HFPG, HSBP, and HLDL, but ranked 10th to 15th for LBMD, KDF, and HBMI, despite the number of DALYs and death ranked first to second for six metabolic risk factors.ConclusionsPopulation aging continuously accelerates the metabolic risk factor driven disease burden in China. Comprehensive and tight control of metabolic risk factors before 20 and 70 may help to mitigate the increasing disease burden and achieve healthy aging, respectively.

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“…Statins reduce the levels of low-density lipoprotein cholesterol and are used as a first-line therapy for CAD prevention. 48 Statins inhibit 3-hydroxy-3-methylglutarylcoenzyme A reductase, a key enzyme in cholesterol synthesis. Numerous RCTs have demonstrated that the use of statins substantially reduces the risk of cardiovascular events.…”

Section: Statinsmentioning

confidence: 99%

Pharmacogenomics in Stroke and Cardiovascular Disease: State of the Art

Ross

Krebs

Paré

et al. 2023

Stroke

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There is considerable interindividual variability in the response to antiplatelet and anticoagulant therapies, and this variation may be attributable to genetic variants. There has been an increased understanding of the genetic architecture of stroke and cardiovascular disease, which has been driven by advancements in genomic technologies and this has raised the possibility of more targeted pharmaceutical treatments. Pharmacogenetics promises to use a patient’s genetic profile to treat those who are more likely to benefit from a particular intervention by selecting the best possible therapy. Although there are numerous studies indicating strong evidence for the effect of specific genotypes on the outcomes of vascular drugs, the adoption of pharmacogenetic testing in clinical practice has been slow. This resistance may stem from sometimes conflicting findings among pharmacogenetic studies, a lack of stroke-specific randomized controlled trials to test the effectiveness of genetically-guided therapies, and the practical and cost-effective implementation of genetic testing within the clinic. Thus, this review provides an overview of the genetic variants that influence the individual responses to aspirin, clopidogrel, warfarin and statins and the different methods for pharmacogenetic testing and guidelines for clinical implementation for stroke patients.

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Treating Coronary Artery Disease: Beyond Statins, Ezetimibe, and PCSK9 Inhibition

Cited by 13 publications

References 73 publications

Angiopoietin-Like Protein 3 (ANGPTL3) Inhibitors in the Management of Refractory Hypercholesterolemia

Angiopoietin-Like Protein 3 (ANGPTL3) Inhibitors in the Management of Refractory Hypercholesterolemia

The temporal trend of disease burden attributable to metabolic risk factors in China, 1990–2019: An analysis of the Global Burden of Disease study

Pharmacogenomics in Stroke and Cardiovascular Disease: State of the Art

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