Low density lipoprotein medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Rim Halaby, M.D. [3]
Overview
Treatment of High LDL
Available Guidelines
The National Cholesterol Education Program (NCEP) publishes the Adult Treatment Panel (ATP) guidelines for detection, evaluation, and treatment of hyperlipidemia in adults.
| Adult Treatment Panel | Release History |
| I | 1988 |
| II | 1993 |
| III | 2001 |
| III Addendum (update) | 2004 |
| IV | 2012 |
Other U.S. guidelines for the management of dyslipidemia are also present. LDL-C target ranges of the following guidelines are not different from the latest ATP guidelines:
- 2008: ADA/ACCF Consensus Statement on Lipoprotein Management in Patients with Cardiometabolic Risk
- 2011: AHA/ACC Guidelines for Secondary Prevention
- 2012: AACE Guidelines for the Management of Dyslipidemia and Prevention of Atherosclerosis
- 2013: ADA Standards of Medical Care in DM
Target Goal
- The American Heart Association, NIH and NCEP provide a set of guidelines for fasting LDL-Cholesterol levels, estimated or measured, and risk for heart disease. According to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III published in 2001, the target goal for LDL-cholesterol after 9- to 12- hour fast are as follows:[1]
| Level mg/dL | Level mmol/L | Interpretation |
|---|---|---|
| <100 | <2.6 | Optimal LDL cholesterol, corresponding to reduced, but not zero, risk for heart disease |
| 100 to 129 | 2.6 to 3.3 | Near optimal LDL level |
| 130 to 159 | 3.3 to 4.1 | Borderline high LDL level |
| 160 to 189 | 4.1 to 4.9 | High LDL level |
| >190 | >4.9 | Very high LDL level, corresponding to highest increased risk of heart disease |
- Nonetheless, ATP III guidelines emphasize on identification of clinical atherosclerotic disease and risk factors that predispose individuals to increased risk of coronary heart disease events. ATP III define clinical atherosclerotic disease as one of the following: [1]
- Clinical coronary heart disease
- Symptomatic carotid artery disease (Transient ischemic attack or stroke of carotid origin)
- Peripheral artery disease
- Abdominal aortic aneurysm[1]
- Categorization of risk and stratification of patients according to clinical atherosclerosis and risk factors play an integral part of ATP III guidelines. Accordingly, LDL-C target levels vary among various risk groups :[1]
| Risk Category (Number of Risk Factors) | 10 Year Risk | LDL-C Goal (mg/dL) |
| 0-1 | <10% | <160 |
| 2+ | ≦20% | <130 (ATP III in 2001) Optional: <100 (Updated ATP III in 2004) |
| CHD or CHD Risk Equivalents | >20% | <100 (ATP III in 2001) Optional: <70 (Updated ATP III in 200) |
- According to ATP III guidelines, the associated risk factors used to define LDL-C target include the following:
- Age ≥ 45 years for men and ≥ 55 years for women
- Smoking
- Hypertension
- HDL-C < 40 mg/dL
- Family history (first degree relative) of premature coronary heart disease at age < 55 years in males or 65 years in females)
2004 Addendum ATP III
- In July 2004, an addendum to the NCEP ATP III guidelines was published following the emergence of data from 5 major clinical trials that addressed new issues and demonstrated novel findings and outcomes.
- Following the addendum, ATP III currently emphasizes on achieving at least 30-40% LDL-C reduction in treating high and moderately high risk patients.[2]
- NCEP ATP IV Guidelines were expected to be published in 2009. However, ATP IV is still currently in the development process.
Significant Trials
- Heart Protection Study
- ALLHAT: Antihypertensive and Lipid-Lowering Treatment To Prevent Heart Attack Trial
- PROVE IT: Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis In Myocardial Infarction
- PROSPER: Prospective Study of Pravastatin in the Elderly at Risk
- ASCOT-LLA: Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm
LDL Cut Off Level to Initiate Therapy
| Risk Category | LDL Goal (mg/dL) |
LDL Level to Initiate TLC (mg/dL) |
LDL Level to Consider Drug Therapy (mg/dL) |
| CHD or CHD risk equivalents (10-year risk >20%) |
<100 | ≥100 | ≥130 |
| 2+ major risk factors (10-year risk ≤20%) |
<130 | ≥130 | 10-year risk 10-20% ≥130 10-year risk <10% ≥160 |
| 0-1 major risk factor | <160 | ≥160 | ≥190 |
Lifestyle Modifications
ATP III recommends the initiation of therapeutic lifestyle changes when LDL is above goal. ATP III recommends the following dietary lifestyle:
- Weight management
- Exercise
- Less than 7% of daily calories derived from saturated fat
- Daily cholesterol intake < 200 mg
- Daily intake of 10-25 g of soluble fiber intake and plant stanols/sterols intake of 2g
Pharmacotherapy
Shown below is a table that summarizes the mechanism of action, percent reduction of LDL and side effects of LDL-c lowering drugs.
| Drug Class | Mechanism of Action | % LDL Reduction | Side Effect |
| Statins | Inhibit HMG-CoA Reductase, rate limiting enzyme of cholesterol synthesis | 18-55 | Hepatotoxicity Myositis |
| Bile Acid Sequestrants | Bind bile inhibiting entero-hepatic circulation | 15-30 | GI distress Nausea Constipation Impaired absorption of fat soluble vitamins and other drugs |
| Niacin ( Vit B3) | Inhibits lipolysis in adipose tissue | 5-25 | Facial flushing Hyperglycemia Hyperuricemia Hepatotoxicity |
| Fibrates | Upregulate lipoprotein lipase | 5-20 | Myositis Hepatotoxicity Gallstones |
| Ezetimibe | Inhibit intestinal cholesterol absorption (synergistic effect with statin) | 17-20 | GI distress Headache Atrial fibrillation Myalgia Constipation |
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001). "Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III)". JAMA. 285 (19): 2486–97. PMID 11368702.
- ↑ Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB; et al. (2004). "Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines". Circulation. 110 (2): 227–39. doi:10.1161/01.CIR.0000133317.49796.0E. PMID 15249516.