Lichtlen P R
Departement für Innere Medizin, Medizinische Hochschule Hannover.
Schweiz Med Wochenschr. 1991 Dec 28;121(51-52):1922-31.
Primary preventive drug treatment of coronary artery disease (CAD) has gained importance in recent years as more efficient lipid lowering drugs and substances with new mechanisms become available, e.g. calcium entry blockers and antioxidants. For lipid lowering drugs, the exact mechanism of action is still not clear; the results of quantitated coronary angiography (QCA) revealing a small but significant increase in luminal size in stenotic areas can be explained both by stabilization of endothelial function (increased EDRF production)--as demonstrated in animal studies--leading to a decrease in basal tone, and by a decrease in plaque volume (so far not evidenced by QCA in man). Calcium entry blockers and antioxidants inhibit the formation of new atherosclerotic lesions, mainly by improving cholesterol excretion from vascular smooth muscle cells and macrophages into the extracellular space, and by suppression of proliferation and differentiation of vascular smooth muscle cells. The ensuing reduction of cardiac events is not yet proven for calcium entry blockers and also needs further confirmation for lipid lowering drugs; the difficulty of studies looking for clinical endpoints (myocardial infarction on sudden coronary death, unstable angina) lies in the very slow anatomical progression of CAD as demonstrated by QCA, demanding large numbers of patients and long intervals to demonstrate statistical significance.
近年来,随着更有效的降脂药物以及具有新作用机制的物质(如钙通道阻滞剂和抗氧化剂)的出现,冠状动脉疾病(CAD)的一级预防性药物治疗变得越发重要。对于降脂药物,其确切作用机制仍不明确;定量冠状动脉造影(QCA)结果显示狭窄区域管腔大小有小幅但显著的增加,这既可以通过内皮功能的稳定(增加内皮舒张因子产生)来解释——正如动物研究所示——从而导致基础张力降低,也可以通过斑块体积减小来解释(目前在人体中QCA尚未证实)。钙通道阻滞剂和抗氧化剂主要通过改善胆固醇从血管平滑肌细胞和巨噬细胞向细胞外空间的排泄,以及抑制血管平滑肌细胞的增殖和分化来抑制新的动脉粥样硬化病变形成。钙通道阻滞剂能否降低心脏事件发生率尚未得到证实,降脂药物也需要进一步确认;寻找临床终点(心肌梗死、心源性猝死、不稳定型心绞痛)的研究难点在于,如QCA所示,CAD的解剖学进展非常缓慢,这需要大量患者和长时间的观察才能显示出统计学意义。