TARGETED PREVENTION OF CORONARY-ARTERY DISEASE - PHARMACOLOGICAL CONSIDERATIONS IN MULTIMODALITY TREATMENT

Treatment of hypercholesterolemia with HMG-CoA-reductase inhibitors ha s revolutionized medical intervention towards the prevention of corona ry artery disease. There is a wide spectrum of patients with diverse u nderlying clinical conditions that may benefit from treatment using th ese agents. These include patients with multiple risk factors, individ uals following major vascular events, and those with special condition s that are associated with accelerated atherosclerosis. The latter inc lude patients with severe, dominantly inherited hypercholesterolemia, patients with major organ dysfunction such as chronic renal failure, a nd individuals after transplantation. Multimodality intervention inclu des behavior modification and mechanical as well as pharmacological tr eatment. It is aimed at several important targets: cholesterol reducti on, control of hypertension and diabetes, improvement of myocardial co ntractility, reduction of infarct size, and control of hemostasis. Mos t of these patients require multiple drugs, which may interact at the pharmacodynamic (efficacy and safety) as well as pharmacokinetic level s. These potential interactions should be considered while planning an d implementing preventive measures for an individual as well as for th e community. The beneficial effects and the potential hazardous intera ctions between HMG-CoA reductase inhibitors and other medications are presented and discussed using two models: heterozygous familial hyperc holesterolemia and major organ transplantation. Although there is a pa rtial overlap in the medications used for the treatment of these two c onditions, some of them differ. The interaction between HMG-CoA reduct ase inhibitors and other cholesterol-lowering agents, mainly fibrates, is discussed in the first model summarizing data from controlled clin ical trials. The interaction with cyclosporin A is presented using the second model. A potential benefit of fluvastatin, as compared with ot her currently available HMG-CoA reductase inhibitors, which may be rel ated to its relatively short plasma half-life and low systemic exposur e, is discussed.