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