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Chapter 35: Agents Used in Dyslipidemia

INTRODUCTION

Atherosclerosis is the leading cause of death for both men and women in the Western world. Drugs discussed in this chapter prevent the sequelae of atherosclerosis (heart attacks, angina, peripheral arterial disease, ischemic stroke) and decrease mortality in patients with a history of cardiovascular disease and hyperlipidemia. Although the drugs are generally safe and effective, they can cause problems, including drug-drug interactions and toxic reactions in skeletal muscle and the liver.

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HYPERLIPOPROTEINEMIA

A. Pathogenesis

Premature or accelerated development of atherosclerosis is strongly associated with elevated concentrations of certain plasma lipoproteins, especially the low-density lipoproteins (LDLs) that participate in cholesterol transport. A depressed level of high-density lipoproteins (HDLs) is also associated with increased risk of atherosclerosis. In some families, hypertriglyceridemia is similarly correlated with atherosclerosis. Chylomicronemia, the occurrence of chylomicrons in the serum while fasting, is a recessive trait that is correlated with a high incidence of acute pancreatitis and managed by restriction of total fat intake (Table 35–1).

TABLE 35–1Primary hyperlipoproteinemias and their drug treatment.
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TABLE 35–1 Primary hyperlipoproteinemias and their drug treatment.
Condition/Cause Manifestations, Cause Single Drug Drug Combination
Primary chylomicronemia Chylomicrons, VLDL increased; deficiency in LPL or apoC-II Dietary management (+ omega-3 fatty acids, niacin, or fibrate) Niacin plus fibratea
Familial hypertriglyceridemia
 Severe VLDL, chylomicrons increased; decreased clearance of VLDL Omega-3 fatty acids, niacin or fibrate Niacin plus fibrate
 Moderate VLDL increased, chylomicrons may be increased; increased production of VLDL Omega-3 fatty acids, niacin or fibrate Niacin plus fibrate
Familial combined hyperlipoproteinemia Increased hepatic apoB and VLDL production    
  VLDL increased Omega-3 fatty acids, niacin, fibrate, statin Two or 3 of the individual drugs
  LDL increased Niacin, statin, ezetimibe Two or 3 of the individual drugs
  VLDL, LDL increased Omega-3 fatty acids, niacin, statin Statin plus niacin or plus fibrate in select patients onlyb
Familial dysbetalipoproteinemia VLDL remnants, chylomicron remnants increased; deficiency in apoE Omega-3 fatty acids, fibrate, statin, or niacin Fibrate plus niacin, or either plus statin.
Familial hypercholesterolemia LDL increased; defect in LDL receptors    

 Heterozygous

 Homozygous

  

Statin, resin, niacin, ezetimibe

Niacin, atorvastatin, rosuvastatin, ezetimibe, mipomersen, or lomitapide, PCSK9 inhibitors (alirocumab, evolocumab

Two or 3 of the individual drugs

Niacin plus statin plus ezetimibe

a Single-drug therapy with marine omega-3 dietary supplement should be evaluated before drug combinations are used.

b Fibrates offer no additional CV risk reduction in patients with elevated VLDL already on a statin in spite of improved VLDL levels (ACCORD lipid trial); selected patients may benefit from adding fibrate to statin.

Modified with permission from Katzung BG, Vanderah TW: Basic & Clinical Pharmacology, 15th ed. New York, NY: McGraw Hill; 2021.

Regulation of plasma lipoprotein levels involves a complex interplay of dietary fat intake, hepatic processing, and utilization in peripheral tissues (Figure 35–1...

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