AMG 145, a Monoclonal Antibody Against PCSK9, Facilitates Achievement of National Cholesterol Education Program–Adult Treatment Panel III Low-Density Lipoprotein Cholesterol Goals Among High-Risk Patients

Desai, Nihar R.; Giugliano, Robert P.; Zhou, Jing; Kohli, Payal; Somaratne, Ransi; Hoffman, Elaine; Liu, Thomas T.; Scott, Robert C.; Wasserman, Scott M.; Sabatine, Marc S.

doi:10.1016/j.jacc.2013.09.048

Cited by 50 publications

(7 citation statements)

References 6 publications

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“…Metabolic syndrome was diagnosed using the criteria suggested by the Third National Cholesterol Education Program (NCEP) report. In this method, the criteria for the diagnosis of metabolic syndrome having three or more than five criteria including waist circumference greater than or equal to 102 cm, hypertension (systolic ≥130 mmHg and diastolic ≥85 mmHg), triglycerides greater than or equal to 150 (mg/dL), HDL cholesterol greater than or equal to 40 (mg/dL), and fasting blood glucose greater than or equal to 100 mg/dL [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

Evaluation of different types of arsenic methylation and its relationship with metabolic syndrome in an area chronically exposed to arsenic

Kazemifar

Shafikhani

Mozhdehipanah

et al. 2020

Environ Anal Health Toxicol

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Evidence suggests that the relationship between arsenic metabolism and diseases, including metabolic syndrome, is complex. The aim of this study was to evaluate the different types of arsenic methylation and its association with metabolic syndrome in an arsenic endemic area. A cross-sectional study was conducted on 132 subjects from Shahid-Abad Village, Qazvin province, Iran (arsenic endemic area). Demographic characteristics, metabolic syndrome, and urinary arsenic species, including iAs (inorganic arsenic), MMA (monomethylarsonic acid), and DMA (dimethylarsinic acid) were measured for all patients and their relationship was analyzed by appropriate statistical methods. In this study, 34.5% of the participants had metabolic syndrome. The decrease in %MMA, increase in %DMA and increase in secondary methylation index (DMA/MMA) were associated with increased risk of metabolic syndrome (p<0.05). We did not find any association between the incidence of metabolic syndrome with primary methylation index (MMA/iAs) and %iAs (p>0.05). This study showed that the prevalence of metabolic syndrome was significantly higher in people with metabolic syndrome than in the general population. A closer examination revealed that the secondary methylation index is related to the metabolic syndrome and its components. Given the higher prevalence of cardiovascular disease and diabetes in patients with metabolic syndrome, it is necessary to change the pathogenesis of the disease using comprehensive management methods for decreasing patient complications.

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Section: Methodsmentioning

confidence: 99%

Evaluation of different types of arsenic methylation and its relationship with metabolic syndrome in an area chronically exposed to arsenic

Kazemifar

Shafikhani

Mozhdehipanah

et al. 2020

Environ Anal Health Toxicol

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“…The inhibition of PCSK9 leads to higher levels of hepatic LDLR, which causes more efficient clearance of LDL from the circulation and drastic lowering of LDL-c levels. As shown in the most recent phase II clinical trials [44–46] and reports from the ongoing phase III trials [47,48 ▪ ,49–51], PCSK9 inhibition via mAb injection once every 2 or 4 weeks results in a 50–65% drop in LDL-c, with small positive effects on HDL-c and triglyceride levels. Similar results were also shown in a phase I trial using small interfering RNA (siRNA) to inhibit PCSK9 production [16 ▪ ].…”

Section: Cross-talk Between Low-density Lipoprotein Receptor and Pcskmentioning

confidence: 97%

PCSK9 inhibition to reduce cardiovascular disease risk

Tavori

Giunzioni

Fazio

2015

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of review Review novel insights into the biology of proprotein convertase subtilisin/kexin 9 (PCSK9) that may explain the extreme efficiency of PCSK9 inhibition and the unexpected metabolic effects resulting from PCSK9 monoclonal antibody therapy, and may identify additional patients as target of therapy. Recent findings For over 20 years, the practical knowledge of cholesterol metabolism has centered around cellular mechanisms, and around the idea that statin therapy is the essential step to control metabolic abnormalities for cardiovascular risk management. This view has been embraced by the recent AHA/ACC guidelines, but is being challenged by recent studies including nonstatin medications and by the development of a new class of cholesterol-lowering agents that seems destined to early US Food and Drug Administration approval. The discovery of PCSK9 – a circulating protein that regulates hepatic low-density lipoprotein (LDL) receptor and serum LDL cholesterol levels – has led to a race for its therapeutic inhibition. Recent findings on PCSK9 regulation and pleiotropic effects will help identify additional patient groups likely to benefit from the inhibitory therapy and unravel the full potential of PCSK9 inhibition therapy. Summary Injectable human monoclonal antibodies to block the interaction between PCSK9 and LDL receptor are demonstrating extraordinary efficacy (LDL reductions of up to 70%) and almost the absence of any side-effects. A more moderate effect is seen on other lipoprotein parameters, with the exception of lipoprotein(a) levels. We describe mechanisms that can explain the effect on lipoprotein(a), predict a potential effect on postprandial triglyderides, and suggest a new category of patients for anti-PCSK9 therapy.

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“…It reduced dose-dependently the LDL-C concentration by 39–66% compared with placebo. At the end of the 12 weeks of the LAPLACE-TIMI 57 study, over 90% of patients at high risk achieved the recommended LDL-C values of < 70 mg/dl with evolocumab at doses of 140 mg every 2 weeks and ≥ 280 mg every 4 weeks [63]. Apart from that, it lowered the level of lipoprotein(a) (Lp(a)), which is a proven important risk factor in the development of CVD [64, 65].…”

Section: Antibodies Targeting Pcsk9mentioning

confidence: 99%

PCSK9 inhibitors – from discovery of a single mutation to a groundbreaking therapy of lipid disorders in one decade

Jaworski¹,

Jankowski²,

Kosior³

2017

aoms

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Hypercholesterolemia is one of the main risk factors for coronary heart disease and significantly contributes to the high mortality associated with cardiovascular diseases. Statin therapy represents the gold standard in the reduction of low-density lipoprotein cholesterol concentration. Nevertheless, many patients still cannot achieve the recommended target levels, due to either inadequate effectiveness or intolerance of these drugs. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as a promising option in lipid-lowering treatment. After confirmation of their efficacy and safety in clinical trials, evolocumab and alirocumab received approval from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for introduction into clinical practice. In this review, we present a history of the development and mechanisms of action, as well as the results of the most important studies concerning PCSK9 inhibitors.

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AMG 145, a Monoclonal Antibody Against PCSK9, Facilitates Achievement of National Cholesterol Education Program–Adult Treatment Panel III Low-Density Lipoprotein Cholesterol Goals Among High-Risk Patients

Abstract: PCSK9 inhibition with AMG 145 enables high-risk patients to achieve established lipid goals. If this therapy demonstrates efficacy for reducing cardiovascular events with a favorable safety profile in ongoing phase 3 trials, we believe it will have major public health implications.

Cited by 50 publications

References 6 publications

Evaluation of different types of arsenic methylation and its relationship with metabolic syndrome in an area chronically exposed to arsenic

Evaluation of different types of arsenic methylation and its relationship with metabolic syndrome in an area chronically exposed to arsenic

PCSK9 inhibition to reduce cardiovascular disease risk

PCSK9 inhibitors – from discovery of a single mutation to a groundbreaking therapy of lipid disorders in one decade

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