Can antihypertensive drugs reduce atherosclerosis and its clinical complications?

Several classes of antihypertensive drugs, including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, alpha 1-blockers, and a combined calcium antagonist/alpha 1-blocker, have been shown to reduce atherosclerosis in hypercholesterolemic animals. Although the exact mechanism of action of these drugs has not been described, certain findings are of particular interest. All of these drugs have the ability to inhibit cellular growth. ACE inhibitors appear to be antiatherosclerotic in several species including the low density lipoprotein (LDL)-deficient Watanabe heritable hyperlipidemic rabbit, and their effects appear to be mediated through both angiotensin II inhibition and bradykinin enhancement. Calcium antagonists may influence primarily the development of new atherosclerotic lesions and their action may be species specific and, at least in part, dependent on the integrity of the LDL receptor. The action of alpha 1-blockers and of a combined calcium antagonist/alpha 1-blocker in hypercholesterolemic animals is probably related in part to their cholesterol-lowering properties. Whether any of the antihypertensive drugs can affect atherosclerosis in humans remains to be determined. Clinical trials are in progress to examine their effects on the course of coronary heart disease and on surrogate endpoints of atherosclerosis such as those demonstrable by angiography and Doppler-ultrasound techniques. Although the results of trials involving such surrogate markers will be of great interest, the findings will need to be interpreted with caution because they may not necessarily be predictive of either the course of atherosclerosis or its clinical complications.