Hyperlipoproteinemia medical therapy

Lipoprotein Disorders Microchapters
Patient Information
Overview
Causes
Classification Hyperlipoproteinemia Hypolipoproteinemia
Treatment

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hardik Patel, M.D.

Overview

Hyperlipidemia requires early detection, careful evaluation and aggressive treatment with combination of therapeutic lifestyle changes and lipid-lowering drug therapies to reduce the risk of cardiovascular and cerebrovascular complications.

Medical Therapy for Adults

Original Recommendations of the National Cholesterol Education Program (NCEP) ATP III for Medical Therapy of Hyperlipidemia in Adults (DO NOT EDIT)

• Obtain complete lipid profile after 9 to 12-hour fast.

Detect Presence of Coronary Heart Disease (CHD) Risk Equivalent

1. Previous personal history of clinical CHD
2. Clinical carotid artery disease
3. Abdominal aortic aneurysm
4. Peripheral arterial disease
5. Diabetes

Determine Presence of Major Risk Factors

(Other than LDL)

1. Hypertension (BP≥140/90 mmHg or on antihypertensive medication)
2. Cigarette smoking
3. Low HDL-cholesterol (<40 mg/dL)
   • HDL-cholesterol ≥60 mg/dL counts as a "negative" risk factor and removes one risk factor from the total count.
4. Age (men ≥45 years; women ≥55 years)
5. Family history of premature CHD in first degree relative (CHD in men <55 years; CHD in women <65 years)

If 2+ major risk factors (other than LDL) are present without CHD or CHD risk equivalent, assess 10-year (short-term) CHD risk using Framingham Risk Score. The Framingham Risk Score is based on data obtained from the Framingham Heart Study. There are two Framingham Risk Scores, one for men and one for women. Three levels of 10-year risk:

Low risk	<10%
Intermediate risk	10 - 20%
High risk (CHD risk equivalent)	>20%

Determine Risk Category, LDL Goal of Therapy, Level for Therapeutic Lifestyle Changes (TLC), and Level for Drug 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

Therapeutic Lifestyle Changes (TLC)

Therapeutic lifestyle changes (TLC) should be initiated, if LDL level is above goal.

1. TLC diet - consists of saturated fat <7% of calories, cholesterol <200 mg/day, increased viscous (soluble) fiber (10-25 g/day), and plant sterols (2g/day) to enhance LDL lowering.
2. Weight management
3. Increased physical activity

Drug Therapy

Drug therapy should be initiated, if LDL exceeds levels shown in above table. Initiate drug simultaneously with TLC for CHD and CHD equivalents, whereas add drug to TLC after 3 months for other risk categories.

Drug Class	Agents (Daily Doses)	Effects on Lipid	Side Effects	Contraindications
Statins (HMG-CoA reductase inhibitors)	Lovastatin (20-80 mg) Pravastatin (20-40 mg) Simvastatin (20-80 mg) Fluvastatin (20-80 mg) Atorvastatin (10-80 mg) Cerivastatin (0.4-0.8 mg)	Decrease LDL Increase HDL Decrease TG	Myopathy Elevated liver enzymes	Absolute: Active or chronic liver disease Relative: Concomitant use of cyclosporine, macrolide antibiotics, anti-fungal agents, cytochrome P-450 inhibitors
Bile acid sequestrants	Cholestyramine (4-16 g) Colestipol (5-20 g) Colesevelam (2.6-3.8 g)	Decrease LDL Increase HDL No change or increase TG	GI distress Constipation Decreased absorption of other drugs	Absolute: Dysbetalipoproteinemia TG >400 mg/dL Relative: TG >200 mg/dL
Nicotinic acid (Niacin)	Immediate release niacin (1.5-3 gm) Extended release niacin (1-2 g) Sustained release niacin (1-2 g)	Increase HDL Decrease TG Decrease LDL	Flushing Hyperglycemia Hyperuricemia Hepatotoxicity Upper GI distress	Absolute: Chronic liver disease Severe gout Relative: Diabetes Hyperuricemia Peptic ulcer disease
Fibric acids (Fibrates)	Gemfibrozil (1.2 g) Clofibrate (2 g) Fenofibrate (200 mg)	Decrease TG Increase HDL	Dyspepsia Gallstones Myopathy	Absolute: Severe hepatic disease Severe renal disease

(LDL=LDL cholesterol, HDL=HDL cholesterol, TG=Triglycerides)

Treatment of Elevated Triglycerides

• In case of hyperlipidemia with elevated triglycerides (≥150 mg/dL), primary aim of therapy is to reach LDL goal, intensify weight management and increase physical activity.

• If triglycerides are ≥200 mg/dL after LDL goal is reached, set secondary goal for non-HDL cholesterol (total - HDL) 30 mg/dL higher than the LDL goal for respective categories.

Risk Category	LDL Goal (mg/dL)	Non-HDL Goal (mg/dL)
CHD or CHD risk equivalents (10-year risk >20%)	< 100	< 130
2+ major risk factors (10-year risk ≤20%)	< 130	< 160
0-1 major risk factor	< 160	< 190

1. If triglycerides are 200-499 mg/dL after LDL goal is reached, consider adding drug if needed to reach non-HDL goal:
   • Intensify therapy with LDL-lowering drug
   • Add niacin or fibrate to further lower triglycerides
2. If triglycerides are ≥500 mg/dL, first lower triglycerides to prevent pancreatitis:
   • Very low-fat diet (<15% of calories from fat)
   • Intensified weight management and increased physical activity
   • Add niacin or fibrate
   • When triglycerides reach <500 mg/dL, turn to LDL-lowering drug

Treatment of Low HDL Cholesterol (<40 mg/dL)

First reach LDL goal, intensify weight management, and increase physical activity; then if triglycerides are 200-499 mg/dL, achieve non-HDL goal and if triglycerides are <200 mg/dL (isolated low HDL) in CHD or CHD equivalent, add niacin or fibrate.

Treatment of the Metabolic Syndrome

• Identification of the metabolic syndrome (any 3 of the following):
  1. Abdominal obesity - waist circumference of >102 cm (>40 in) in men and >88 cm (>35 in) in women
  2. Serum triglyceride level ≥150 mg/dL
  3. HDL cholesterol level of <40 mg/dL in men and <50 mg/dL in women
  4. Blood pressure ≥130/85 mmHg
  5. Fasting glucose ≥110 mg/dL.

• Treat underlying causes:
  • Intensify weight management
  • Increase physical activity.

• Treat lipid and non-lipid risk factors, if they persist despite TLC:
  • Treat hypertension
  • Use aspirin for CHD patients to reduce thromboembolic risk
  • Treat elevated triglycerides and/or low HDL as shown above.

Other Lipid Lowering Agents

Omega-3 Fatty Acids

Drug	Mechanisms of Benefit	Dosage	Advantages	Side Effects	Contraindications
Omega-3 fatty acids	↓ hepatic lipogenesis ↓ plasma lipoprotein lipase activity ↑ hepatic mitochondrial and peroxisomal beta-oxidation Inhibition of acyl CoA:1,2-diacylglycerol acyltransferase enzyme EPA and DHA are poor enzyme substrates for triglyceride synthesis in liver and inhibits esterification of other fatty acids.	3 g/day of EPA and DHA	↓ VLDL, ↓ TG by ≥50%	Bleeding, at high doses Fishy smell, can be reduced by freezing of medication trying different formulation taking medication with food Nausea	Hypersensitivity

(↑ - Increase, ↓ - Decrease)

Ezetimibe

Ezetimibe is a new class of lipid lowering agents. It inhibits intestinal absorption of cholesterol. It has been approved as a monotherapy or in combination with statins to treat hypercholesterolemia. It has also been approved in combination with fenofibrate to treat mixed hyperlipidemia.

Medical Therapy in Children and Adolescents

Click on the respective microchapter to read more about it:

• Drug Therapy
• Statins
• Adjuvant Therapies

A Trial Based Approach to Statin Guidelines

Shown below is a table suggesting an approach to the use of statin according to different trials.

Patient Group	Supporting Trials
Secondary prevention
High-quality randomized clinical trial data support the use of statin therapy as an effective adjunct to diet, exercise, and smoking cessation for secondary prevention patients with a history of myocardial infarction, stroke, or clinically apparent atherosclerosis.	4S, CARE, LIPID, PROSPER, HPS
High-quality randomized clinical trial data in secondary prevention support maximizing the intensity of statin treatment and maintaining compliance with the treatment regimen.	PROVE-IT, TNT, IDEAL, A to Z, SEARCH
Primary prevention
High-quality randomized clinical trial data support the use of statin therapy as an effective adjunct to diet, exercise, and smoking cessation in the setting of primary prevention for middle-aged and older individuals with elevated low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, elevated C-reactive protein, or multiple risk factors inclusive of diabetes and hypertension.	WOSCOPS, MEGA, AFCAPS/TexCAPS, CARDS, ASCOT-LLA, JUPITER
Heart failure and renal insufficiency:
High-quality randomized clinical trial data do not support the use of statin monotherapy for adults with isolated heart failure or those underlying hemodialysis.	CORONA, GISSI-HF, 4-D, AURORA
High-quality randomized clinical trial data support the use of statin therapy among adults with chronic renal insufficiency, at least when given in combination with ezetimib.	SHARP
Other conditions:
For adults who do not meet the above criteria, physicians may consider issues such as genetic predisposition or a strong family history of premature coronary disease when making decisions for individual patient. For some patients, such as those suspected of having familial hyperlipidemia, referral to lipid or atherosclerosis specialists may be useful for consideration of further evaluation and the use of statins despite the absence of hard end point trial data.	None-clinical judgement, expert opinion