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1969年Wilson等注意到在双盲试验中用安慰剂代替心得平(Oxprenolol)使18例病人中6例心绞痛严重恶化。二年前已有报告提示突然撤去心得安后发生心肌梗死,并认为这与心得安的突然停用有因果关系;后来以此解释在类似情况下出现的急性严重心肌缺血事故。但这一因果关系难以证实,因为心得安常用于治疗冠心病人的心绞痛,而这类病人特别容易发生这种急性合并症。Miller等已确定此反跳现象的发生率:对20名稳定型心绞痛及证实有冠心病的门诊病人进行双盲交叉研究,以比较心得安与安慰剂的作用。在心得安治疗期(160~320毫克/天)无一例心绞痛加重,也无一例需入院或死亡。此试验设计包括初步剂量摸索期末及12周的交叉治疗期后突然停用心得安。结果2例死亡,1例发生室性心动过速,需电击复律治疗,3例于撤去心得安后14天内休息时有严重心绞痛发作。与用安慰剂相比较,这组病例从心绞痛次数,硝酸甘油用量及运动耐量试验等来看,对心得安的反应良好。有4例于撤去心得安后的14天内,
In 1969 Wilson et al. Noted that placebo instead of oxprenolol in double-blind trials severely worsens the angina in 6 of 18 patients. Two years ago reports of sudden withdrawal of prednisolone were reported as a causal link with sudden discontinuation of propranolol and later explained the occurrence of acute severe myocardial ischemia in similar situations. However, this causal relationship is difficult to confirm because of the usual experience of treating angina pectoris in patients with coronary heart disease, which is particularly vulnerable to this acute comorbid condition. Miller et al. Have determined the incidence of this rebound phenomenon: a double-blind crossover study of 20 stable angina and clinically confirmed outpatients with coronary heart disease to compare the effects of propranolol and placebo. There was no angina pectoris during the treatment period (160-320 mg / day), nor was there any need for hospitalization or death. The trial design consisted of a sudden withdrawal of propranolol after the initial dose escalation at the end of the 12-week cross-treatment period. Results Two patients died and one patient had ventricular tachycardia. Electrical shock therapy was required. Three patients had severe angina pectoris at rest within 14 days after withdrawal of propofol. Compared with placebo, this group of patients from the angina number, nitroglycerin consumption and exercise tolerance test point of view, the response to propranolol good. There are 4 cases in the withdrawal of the mind after 14 days,