Lipid Lowering Drugs

Reference work entry
First Online:

Abstract

Fat is an important nutrient in our diets. The adverse cardiovascular events as a result of elevated levels of lipoproteins in the blood led to the concept of lipid-lowering medications. Non-statin agents such as niacin, fibrates, fish oils, and ezetimibe are well known as lipid-lowering agents. In various clinical trials such as WOSCOPS (West of Scotland Coronary Prevention Study), JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), and other trials, the concept of lowering of cholesterol-containing apolipoprotein B lipoproteins was achieved by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG Co A) reductase inhibitors or statins. Statins lower the LDL-C and thereby reduce cardiovascular morbidity and mortality. Many patients may not achieve their target levels of LDL-C, and as a result, there remains an LDL-associated residual risk. Loss-of-function mutations of the PCSK9 gene discovered were linked to low plasma LDL-C levels and a reduction of cardiovascular risk. In November of 2013, the American College of Cardiology (ACC) and American Heart Association (AHA) released four new guidelines such as Guideline on Risk Assessment, Guideline on Managing Blood Cholesterol, Guideline on Lifestyle Management, and Guideline for the Management of Overweight and Obesity which deal with the prevention of CVD by better assessing risk and by managing cholesterol, lifestyle, and weight. The central role of proprotein convertase subtilisin/kexin type 9 in the regulation of cholesterol homeostasis by increasing the endosomal and lysosomal degradation of hepatic LDLR (low-density lipoprotein receptor) has now been identified. Loss-of-function mutations of PCSK9 gene were reported to be linked to low plasma LDL-C levels and marked reduction of cardiovascular risk.

Keywords

High Density Lipoprotein Cholesterol Framingham Risk Score Atherosclerotic Cardiovascular Disease Multiple Risk Factor Intervention Trial ASCVD Risk 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Glossary of Terms

Low density lipoprotein (LDL)

Is the main carrier of plasma cholesterol and a major component of atherosclerotic plaque. It can be isolated by density gradient centrifugation.

LDL receptor

Mosaic protein of 839 amino acids responsible for uptake of LDL.

Abbreviations

ACC

American College of Cardiology

ACCORD Study

Effects of combination lipid therapy in type 2 diabetes mellitus

AFCAPS/TexCAPS

Air Force/Texas Coronary Atherosclerosis Prevention Study

AHA

American Heart Association

ARBITER 2 Trial

Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended release niacin, an atherosclerosis progression in secondary prevention patients treated with statins

ASCOT-LLA

Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm

ASCVD

Atherosclerotic cardiovascular disease risk

COURAGE Trial

Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients. A post hoc analysis from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation)

CVD

Cardiovascular disease

dal-OUTCOMES

Effects of dalcetrapib in patients with a recent acute coronary syndrome

ENHANCE Trial

Comparison of ezetimibe plus simvastatin vs. simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia: design and rationale of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial

HMG Co

A 3-hydroxy-3-methylglutaryl-coenzyme

JELIS Study

Effects of EPA on coronary artery disease in hypercholesterolemia patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS)

JUPITER

Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin

LDL-C

Low-density lipoprotein cholesterol

LDLR

Low-density lipoprotein receptor

MEGA

Primary prevention of cardiovascular disease with pravastatin in Japan

MENDEL Study

Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolemia (MENDEL): a randomized, double-blind, placebo-controlled, phase 2 study

OSLER Trial

Efficacy and safety of long-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) Randomized trial

PCSK 9

Proprotein convertase subtilisin/kexin type 9

Phospholipids

Phospholipids are lipids containing, in addition to fatty acids and an alcohol, a phosphoric acid residue and a nitrogen containing base

SATURN

Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin vs. Atorvastatin

siRNA

Small interfering ribonucleic acid. Short (21–26 nucleotides) double-stranded RNAs that inhibit gene expression by directing destruction of complementary mRNAs; production of siRNA is triggered by double-stranded RNA

SREBP

Sterol-responsive element-binding protein

Statins

Statins are drugs which inhibit HMG-CoA reductase, thus upregulating LDL receptors

WOSCOPS

West of Scotland Coronary Prevention Study

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Further Reading

  1. Ballantyne CM (2014) Clinical lipidology: a companion to Braunwald’s heart disease. Saunders and Co., PhiladelphiaGoogle Scholar
  2. Downs JR, Clearfield M, Weis S et al (1998) Primary prevention of acute coronary events with lovastatin in men with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 279:1615–1622CrossRefPubMedGoogle Scholar
  3. Dias CS, Shaywitz AJ, Wasserman SM et al (2012) Effects of AMG 145 on low density lipoprotein cholesterol level results from 2 randomized double-blind, placebo-controlled, ascending dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J Am Coll Cardiol 60:1888–1898CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Departments of Pathology and PharmacologyLoyola University Health SystemMaywoodUSA
  2. 2.Departments of Pathology and OphthalmologyLoyola University Health SystemMaywoodUSA
  3. 3.Department of PathologyLoyola University Health SystemMaywoodUSA

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