Novel agents in the treatment of atherosclerosis

A recent Biochemical Society Colloquium 'Novel Approaches to the Treatment of Atherosclerosis' discussed some of the potential alternatives to the current lipid-lowering strategies used to influence coronary heart disease morbidity and mortality. Advances in understanding of the conventional low density lipoprotein cholesterol-lowering agents, particulary the fibrates and the statins, from recent experimental and clinical studies, suggest new directions in lipoprotein research. Increased insight into other important determinants of atherosclerosis also indicates the likely requirement for a variety of therapeutic approaches to address plaque stabilisation and rupture. The contributions of oxidised LDL variants and Lipoprotein(a) as risk factors in atherogenesis are assuming increasing importance. Other research has emphasised the many roles of macrophage colony stimulating factor and the opportunities for intervention on smooth muscle cell proliferation. In addition to the difficulties inherent in comparing the virtues of the different categories of novel anti-atherosclerosis agent, other research challenges include development of appropriate animal models and the optimisation of less invasive methods for the measurement of coronary atherosclerosis progression and regression. Other clinical and regulatory issues relate to the choice of surrogate endpoints and the value of shorter studies in high-risk patient populations and of pharmacoeconomic research. While drug development in this area may remain relatively arduous, there are some exciting opportunities in prospect. Because the selection of patients to receive hypocholesterolaemic therapy continues to attract controversy, there is great interest in the direct approaches to influencing atherosclerosis and, hence, addressing the presently unmet medical needs. 1994