Drug therapy and the prevention of atherosclerosis in humans

The results of the World Health Organization Cooperative Trial, the Coronary Drug Project, the Coronary Primary Prevention Trial and the Helsinki Heart Study indicate that clinical expression of coronary artery disease can be delayed with pharmacologic modification of plasma lipoproteins. Change in coronary artery disease can be semiquantitated by repeat arteriograms. Three randomized clinical trials indicate that rate of progression of atherosclerosis, as defined by arteriography, can be reduced, and existing lumen obstruction decreased. Tendon xanthomas occur in hypercholesterolemia, and reduction in xanthoma size with drug therapy suggests an improved atherosclerotic disease state. The clinician has a variety of pharmacologic therapies available. The role of bile acid-binding resins, fibric acid derivatives, hydroxymethylglutaryl coenzyme A reductase inhibitors, nicotinic acid and antioxidants is each unique. Understanding the role of lipoproteins in atherosclerosis will help in selecting the most appropriate therapy for each individual patient. Medications not designed for their lipoprotein effects can significantly alter lipoproteins. Medications, such as nonselective beta blockers, can alter low-density lipoprotein (LDL) subclass distribution with no change in LDL cholesterol content. Such changes may eradicate part of the beneficial cardiovascular effect of beta blockade therapy. In the future, therapeutic choices may depend in part on lipoprotein abnormalities such as lipoprotein (a), apolipoprotein E isoforms, hyperapobetalipoproteinemia, LDL.