Laboratory surrogates for anti-atherosclerotic drug development

Anti-atherosclerotic drug development includes the need for biochemical surrogate markers, because clinical parameters of efficacy are of very limited use early in the development process. Surrogate biochemical markers may provide a basis in Phase II for dose selections for Phase III trials. They may also help to improve selection of the most suitable population for entry to clinical endpoint trials. There is still a great deal of confusion as to the epidemiologic relation of biochemical markers and risk of coronary artery disease and whether altering these markers results in clinical benefit. The primary biochemical surrogate currently used and well accepted by regulatory agencies is low-density lipoprotein (LDL) cholesterol. Apolipoprotein B (apo B) is not as well accepted but, based on clinical trials, may be a better surrogate, because it simultaneously evaluates other atherogenic lipoproteins. Other potential surrogates include various lipid and lipoprotein subpopulations, apolipoproteins, procoagulants, fibrinolytics, inflammatory proteins, adhesion molecules, and lesion lytic enzymes. All of these parameters are involved in either the causation or propagation of the atherothrombotic process.