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钙拮抗剂在动脉粥样硬化中的初步临床经验。维拉帕米高血压动脉粥样硬化研究组。

Preliminary clinical experience with calcium antagonists in atherosclerosis. Verapamil in Hypertension Atherosclerosis Study Investigators.

作者信息

Magnani B, Dal Palù C, Zanchetti A

机构信息

Institute of Cardiology, University of Bologna, Italy.

出版信息

Drugs. 1992;44 Suppl 1:128-33. doi: 10.2165/00003495-199200441-00024.

Abstract

Animal experiments have shown that the administration of calcium antagonists can prevent or slow the progression of atherosclerosis by inhibiting calcium overload and interfering with lipid metabolism and deposition. These encouraging results have prompted clinical trials to evaluate the effects of calcium antagonists (dihydropyridines and diphenylalkylamines) on atherosclerotic plaque formation. In patients with coronary heart disease, several studies have already shown that calcium antagonists can have a positive effect on plaque evolution, while in hypertensive patients no such study has been published to date. The Verapamil in Hypertension Atherosclerosis Study is an ongoing multicentre randomised double-blind parallel group trial comparing the antihypertensive efficacy of verapamil SR 240 mg/day with that of chlorthalidone 25 mg/day in 1464 patients with essential hypertension aged 40 to 65 years. In a randomised subgroup of patients (n = 550), who will be followed up for 3 years, B-mode ultrasonography is being employed to evaluate the effects of the 2 drugs on carotid wall thickness and carotid plaque development. Ultrasonographic evaluations are performed at baseline, after 3 months, and 1, 2 and 3 years after a standardised protocol to determine intimal-medial thickness in 4 segments of the extracranial carotid tree. The most interesting result to date is the high incidence of carotid alterations, with plaques present in 35% and arterial wall thickening in 31.8% of the 311 asymptomatic hypertensive patients processed so far. A preliminary evaluation of the antihypertensive efficacy of the trial medications after 6 months of double-blind treatment indicates a 63.5% response rate to monotherapy and a 7.8% drop-out rate because of drug inefficacy or intolerance.

摘要

动物实验表明,给予钙拮抗剂可通过抑制钙超载以及干扰脂质代谢和沉积来预防或减缓动脉粥样硬化的进展。这些令人鼓舞的结果促使开展临床试验,以评估钙拮抗剂(二氢吡啶类和二苯基烷基胺类)对动脉粥样硬化斑块形成的影响。在冠心病患者中,多项研究已表明钙拮抗剂可对斑块演变产生积极作用,而在高血压患者中,迄今为止尚未发表此类研究。维拉帕米高血压动脉粥样硬化研究是一项正在进行的多中心随机双盲平行组试验,比较240毫克/天缓释维拉帕米与25毫克/天氯噻酮对1464例40至65岁原发性高血压患者的降压疗效。在一个随机分组的患者亚组(n = 550)中,将对其进行3年随访,采用B型超声检查来评估这两种药物对颈动脉壁厚度和颈动脉斑块发展的影响。超声评估在基线时、3个月后以及按照标准化方案在1年、2年和3年后进行,以确定颅外颈动脉树4个节段的内膜中层厚度。迄今为止最有趣的结果是颈动脉病变的高发生率,在目前已接受检查的311例无症状高血压患者中,35%存在斑块,31.8%存在动脉壁增厚。双盲治疗6个月后对试验药物降压疗效的初步评估表明,单药治疗的有效率为63.5%,因药物无效或不耐受导致的退出率为7.8%。

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