アナセトラピブは,ヘテロジゴス型家族性高コレステロール血症 (REALIZE) の患者における脂質修飾療法として:ランダム化,ダブルブラインド,プラセボ対照,第3相試験

John J P Kastelein¹, Joost Besseling¹, Sukrut Shah²

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Lancet (London, England)

|March 7, 2015

まとめ

アナセトラピブは,家族性高コレステロール血症患者のLDLコレステロールを著しく低下させた. これによって心血管疾患の発生が減少するかどうかを確認するためにさらなる研究が必要である.

科学分野:

心血管医学心血管医学
薬理学薬理学とは

背景:

家族性高コレステロール血症 (FH) は,LDLコレステロール (LDL-C) の低濃度を必要とする.
現在の治療法では,FH患者のターゲットとなるLDL-Cレベルを達成することがしばしばできない.
コレステリルエステル転送タンパク質 (CETP) 阻害剤は,スタチンと併用すると,LDL-Cを減少させることができます.

研究の目的:

CETP阻害剤であるアナセトラピブの安全性と有効性を評価する.
ヘテロジゴト性FH患者におけるLDL-Cに対するアナセトラピブの効果を評価する.

主な方法:

多センター,ランダム化,ダブルブラインド,プラセボ対照,第3相研究.
ヘテロジゴス型FHの18~80歳の患者は,アナセトラピブ (100mg) またはプラセボを52週間投与された.
主要アウトカム:ベースラインからLDL-Cのパーセント変化.

主要な成果:

アナセトラピブは52週間にわたってプラセボと比較して平均LDL-Cを36.0%減少させた.
アナセトラピブとプラセボの間のLDL-C減少の違いは-39.7% (p<0.0001) でした.
心血管疾患はアナセトラピブ群ではわずかに増加したが,有害事象の発生率は類似していた.

結論:

1年間のアナセトラピブ治療は,ヘテロジゴト性FH患者で良好に耐えました.
アナセトラピブは,LDL-C濃度の大幅な低下を達成しました.
進行中のアウトカム研究により,これらのLDL-Cの減少が心血管疾患の減少に繋がるかどうかを決定する.

さらに関連する動画

07:54

Cholesterol Efflux Assay

Published on: March 6, 2012

31.0K

09:15

Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles

Published on: November 10, 2017

15.2K

関連する概念動画

01:20

Lipid-Lowering Drugs: Statins and Miscellaneous Agents

1.9K

Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...

1.9K

01:26

Atherosclerosis III: Management

613

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...

613

01:29

Cholesterol: Significance and Regulation

2.0K

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...

2.0K

01:24

Lipid Absorption

3.8K

Dietary triglycerides from chyme in the duodenum are mixed with bile salts produced by the liver to emulsify fats. As a result, large droplets are broken down into smaller ones, increasing the surface area for enzymatic action. Once emulsified, pancreatic lipases hydrolyze the triglycerides into free fatty acids and monoglycerides.
These breakdown products bind with bile salts and lecithin to form micelles, which quickly pass between microvilli to come in close contact with the apical...

3.8K

01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...

01:25

Lipid Catabolism

1.4K

Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...