Retardation of coronary atherosclerosis: the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and other angiographic trials.
A large number of both primary and secondary preventive trials suggest that treatment of elevated plasma lipids may reduce the frequency of coronary heart disease (CHD) events. Meta-analyses indicate that for every 10% reduction of cholesterol, CHD mortality is lowered by 13% and all-cause mortality by 10%. Experience from several angiographic trials also suggests that coronary atherosclerosis can be retarded, and in some instances limited regression induced, by low-density lipoprotein (LDL)-cholesterol reduction and/or high-density lipoprotein (HDL)-cholesterol elevation. Coronary angiographic studies have shown that although the effects on retardation/regression of altherogenic lesions have been small, with luminal diameter changes of around 0.10 mm, the effects on clinical events were more substantial, with reductions of the order of 50%. There is also evidence that it is the mild and moderate lesions that are of particular concern with respect to the occurrence of clinical coronary events. The progression of atherosclerosis and the occurrence of coronary events are probably not exclusively dependent on a lowering of LDL-cholesterol concentrations. Analyses from the Monitored Atherosclerosis Regression Study (MARS), the Cholesterol Lowering Atherosclerotic Study (CLAS), and the Programs on the Surgical Control of the Hyperlipidaemias (POSCH) indicate that triglyceride-rich lipoproteins may also be of importance for the progression of mild/moderate lesions in subjects treated with cholesterol-lowering regimens. Recently, the results of the 5-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) demonstrated that bezafibrate significantly retarded the progression of coronary atheroma and coronary events in young male survivors of myocardial infarction, as assessed by changes in minimum lumen diameter. This positive outcome is most likely due to the beneficial treatment effects on the levels of serum triglycerides (-31%), plasma fibrinogen (-12%), and HDL cholesterol (+9%). The results of the BECAIT on progression of coronary atherosclerosis are comparable with those of two recent angiographic trials with HMG-CoA reductase inhibitors, the Multicenter Anti-Atheroma Study (MAAS), and the Regression Growth Evaluation Statin Study (REGRESS), despite different lipid and metabolic effects. BECAIT is the first controlled angiographic study to show that a fibrate can significantly retard the progression of coronary atherosclerosis. The exact mechanisms by which this occurs remain to be elucidated. However, the results of BECAIT illustrate the importance of factors other than LDL cholesterol in the progression of coronary atherosclerosis.
de Faire
U
U
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Ericsson
C G
CG
Grip
L
L
Nilsson
J
J
Svane
B
B
Hamsten
A
A
D001629:Bezafibrate / Q000627:therapeutic use*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D014280:Triglycerides; D001629:Bezafibrate