Siscovick D S, Raghunathan T E, Psaty B M, Koepsell T D, Wicklund K G, Lin X, Cobb L, Rautaharju P M, Copass M K, Wagner E H
Department of Medicine, University of Washington, Seattle.
N Engl J Med. 1994 Jun 30;330(26):1852-7. doi: 10.1056/NEJM199406303302603.
The results of trials of the primary prevention of coronary heart disease have suggested that treating hypertension with high doses of thiazide diuretic drugs might increase the risk of sudden death from cardiac causes. In contrast, treatment with low doses of thiazide reduces the risk of coronary heart disease.
To examine the association between thiazide treatment for hypertension and the occurrence of primary cardiac arrest, we conducted a population-based case-control study among enrollees of a health maintenance organization. The case patients were 114 persons with hypertension who had a primary cardiac arrest from 1977 through 1990. The control patients were a stratified random sample of 535 persons with hypertension. The patients' treatment was assessed with the use of a computerized pharmacy data base. Records of their ambulatory care were reviewed to determine other clinical characteristics.
The risk of primary cardiac arrest among patients receiving combined thiazide and potassium-sparing diuretic therapy was lower than that among patients treated with a thiazide without potassium-sparing therapy (odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). As compared with low-dose thiazide therapy (25 mg daily), moderate-dose therapy (50 mg daily) was associated with a moderate increase in risk (odds ratio, 1.7; 95 percent confidence interval, 0.7 to 4.5), and high-dose therapy (100 mg daily) was associated with a larger increase in risk (odds ratio, 3.6; 95 percent confidence interval, 1.2 to 10.8) (P value for trend, 0.02). The addition of a potassium-sparing drug to low-dose thiazide therapy was associated with a reduced risk of cardiac arrest (odds ratio, 0.4; 95 percent confidence interval, 0.1 to 1.5).
Both the dose of thiazide drugs and the addition of potassium-sparing drugs influence the risk of primary cardiac arrest. These results may explain the differences in the effect of antihypertensive therapy on mortality from coronary heart disease in previous clinical trials.
冠心病一级预防试验的结果表明，用高剂量噻嗪类利尿药治疗高血压可能会增加心源性猝死的风险。相比之下，低剂量噻嗪类药物治疗可降低冠心病风险。
为研究噻嗪类药物治疗高血压与原发性心脏骤停发生之间的关联，我们在一家健康维护组织的参保人群中开展了一项基于人群的病例对照研究。病例组为1977年至1990年间发生原发性心脏骤停的114例高血压患者。对照组是从535例高血压患者中分层随机抽取的样本。通过计算机化药房数据库评估患者的治疗情况。查阅他们的门诊护理记录以确定其他临床特征。
接受噻嗪类与保钾利尿药联合治疗的患者发生原发性心脏骤停的风险低于未接受保钾治疗的噻嗪类药物治疗患者（比值比为0.3；95%置信区间为0.1至0.7）。与低剂量噻嗪类药物治疗（每日25毫克）相比，中等剂量治疗（每日50毫克）会使风险适度增加（比值比为1.7；95%置信区间为0.7至4.5），高剂量治疗（每日100毫克）会使风险大幅增加（比值比为3.6；95%置信区间为1.2至10.8）（趋势P值为0.02）。在低剂量噻嗪类药物治疗中加用保钾药物与心脏骤停风险降低相关（比值比为0.4；95%置信区间为0.1至1.5）。
噻嗪类药物的剂量以及保钾药物的添加都会影响原发性心脏骤停的风险。这些结果可能解释了先前临床试验中抗高血压治疗对冠心病死亡率影响的差异。
