New strategies in the development of anti-atherosclerotic drugs

The results of several recently completed trials of cardiovascular prevention, by the use of hypolipidemic or anti-platelet compounds, have suggested that new strategies be followed for the development of anti-atherosclerotic drugs. The final outcome of preventive studies with hypolipidemic compounds is markedly influenced by the significance of the achieved hypolipidemia, as well as by the side-effects, some of which, i.e. lithogenicity, may be related to the drugs' mechanism of action. Significant differences may, moreover, exist between the findings in animal models and in humans, particularly by clofibrate and related compounds. The evaluation of drugs active on lipoprotein biosynthesis in the gut (metformin), potent enzyme inhibitors (compactin) and with chelating activity (cetaben), is awaited with interest. In the field of drugs affecting platelets, a selective sensitivity for the major compounds in different vascular areas has been observed. Aspirin appears to be mostly effective in cerebro-vascular prevention. Agents affecting the thrombin-platelet coagulation interaction, i.e. GYKI 14,451, may offer an interesting opportunity for testing the importance of this pathway in clinical thrombosis.