New approaches to atherosclerosis: an overview.
The mechanisms of action and selected agents for a variety of approaches to the treatment of atherosclerosis have been reviewed. In Table I, each approach is listed according to its primary physiological effect. This is a simplification, of course, and some agents, such as ACAT inhibitors, may have primary effects in all of these categories. As one goes from left to right, the benefit of each physiological effect becomes more speculative. There is no question of the benefit of LDL reduction, but less evidence exists for the clinical benefits of HDL elevation. With regard to direct anti-atherosclerotic effects, most approaches have yet to gather clinical data of any type. Perhaps as a result, the degree of medicinal chemistry effort in each area to date declines as one goes from left to right. This situation is changing rapidly, however. As evidence supporting the HDL hypothesis accumulates and knowledge of how to elevate HDL levels grows, very exciting opportunities for medical advances present themselves. Likewise, the knowledge base for nonlipid intervention is growing and very rapid advances are being achieved with the plaque-imaging techniques needed for evaluating such agents in man. Such results can only lead to greater opportunities for pharmacological intervention. Thus, in the future, much greater research effort will likely be dedicated to HDL elevation and nonlipid approaches. Through these efforts, physicians of the future should be armed with several complementary agents that can reduce the risk of cardiovascular disease in all patient populations.
McCarthy
P A
PA
Medicinal Chemistry Department, Central Research, Pfizer, Inc., Groton, CT 06340.
D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000517:prevention & control*; D002784:Cholesterol / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans
D000924:Anticholesteremic Agents; D002784:Cholesterol