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New approaches to atherosclerosis: an overview
1Medicinal Chemistry Department, Central Research, Pfizer, Inc., Groton, CT 06340.
Insights
This review examines atherosclerosis treatments, highlighting LDL reduction as proven and HDL elevation as promising. Future research will focus on HDL and non-lipid interventions for comprehensive cardiovascular disease risk reduction.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Medical Chemistry
Background:
- Atherosclerosis treatment involves various approaches targeting different physiological effects.
- Current strategies include LDL reduction, with growing interest in HDL elevation and non-lipid interventions.
Purpose of the Study:
- To review mechanisms of action and agents for atherosclerosis treatment.
- To assess the speculative benefits and medicinal chemistry efforts for different therapeutic approaches.
Main Methods:
- Review of existing literature on atherosclerosis treatment mechanisms and agents.
- Categorization of approaches based on primary physiological effects.
- Analysis of the current state of clinical data and research effort in each area.
Main Results:
- LDL reduction is a well-established benefit, while HDL elevation shows potential but requires more clinical evidence.
- Direct anti-atherosclerotic effects are largely unproven, with limited clinical data for most novel approaches.
- Medicinal chemistry efforts correlate with the perceived clinical benefit, with declining effort for more speculative approaches.
Conclusions:
- Future research will likely prioritize HDL elevation and non-lipid interventions due to accumulating evidence and technological advancements.
- Developing complementary agents for HDL elevation and non-lipid approaches will enhance cardiovascular disease risk reduction across all patient populations.
- Advances in plaque-imaging techniques will facilitate the evaluation of novel anti-atherosclerotic agents in clinical trials.
Abstract:
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.