Borhani N O, Mercuri M, Borhani P A, Buckalew V M, Canossa-Terris M, Carr A A, Kappagoda T, Rocco M V, Schnaper H W, Sowers J R, Bond M G
Department of Internal Medicine, School of Medicine, University of California at Davis, USA.
JAMA. 1996 Sep 11;276(10):785-91.
To compare the rate of progression of mean maximum intimal-medial thickness (IMT) in carotid arteries, using quantitative B-mode ultrasound imaging, during antihypertensive therapy with isradipine vs hydrochlorothiazide.
Randomized, double-blind, positive-controlled trial.
Nine medical center clinics.
A total of 883 patients with baseline mean +/- SD systolic and diastolic blood pressure (SBP and DBP, respectively) of 149.7 +/- 16.6 and 96.5 +/- 5.1 mm Hg, age of 58.5 +/- 8.5 years, and maximum IMT of 1.17 +/- 0.20 mm.
Twice daily doses of isradipine (2.5-5.0 mg) or hydrochlorothiazide (12.5-25 mg). MAIN OUTCOME MEASURE (PRIMARY END POINT): Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years.
There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years (P=.68). There was a higher incidence of major vascular events (eg, myocardial infarction, stroke, congestive heart failure, angina, and sudden death) in isradipine (n=25; 5.65%) vs hydrochlorothiazide (n=14; 3.17%) (P=.07), and a significant increase in nonmajor vascular events and procedures (eg, transient ischemic attack, dysrhythmia, aortic valve replacement, and femoral popliteal bypass graft) in isradipine (n=40; 9.05%) vs hydrochlorothiazide (n=23; 5.22%) (P=.02). At 6 months, mean DBP decreased by 13.0 mm Hg in both groups, and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine (P=.002); the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine.
The rate of progression of mean maximum IMT in carotid arteries, the surrogate end point in this study, did not differ between the 2 treatment groups. The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further.
采用定量B型超声成像技术，比较在使用伊拉地平与氢氯噻嗪进行抗高血压治疗期间，颈动脉平均最大内膜中层厚度（IMT）的进展速率。
随机、双盲、阳性对照试验。
9家医疗中心诊所。
总共883例患者，其基线平均收缩压和舒张压（分别为SBP和DBP）为149.7±16.6和96.5±5.1mmHg，年龄为58.5±8.5岁，最大IMT为1.17±0.20mm。
每日两次服用伊拉地平（2.5 - 5.0mg）或氢氯噻嗪（12.5 - 25mg）。主要观察指标（主要终点）：12个颈动脉病灶点在3年内平均最大IMT的进展速率。
在3年期间，伊拉地平与氢氯噻嗪之间平均最大IMT的进展速率没有差异（P = 0.68）。伊拉地平组（n = 25；5.65%）的主要血管事件（如心肌梗死、中风、充血性心力衰竭、心绞痛和猝死）发生率高于氢氯噻嗪组（n = 14；3.17%）（P = 0.07），并且伊拉地平组（n = 40；9.05%）的非主要血管事件和手术（如短暂性脑缺血发作、心律失常、主动脉瓣置换和股腘动脉搭桥术）显著多于氢氯噻嗪组（n = 23；5.22%）（P = 0.02）。6个月时，两组的平均DBP均下降了13.0mmHg，氢氯噻嗪组的平均SBP下降了19.5mmHg，伊拉地平组下降了16.0mmHg（P = 0.002）；两组之间SBP的差异在整个研究过程中持续存在，但无法解释接受伊拉地平治疗的患者血管事件发生率增加的原因。
本研究的替代终点——颈动脉平均最大IMT的进展速率在两个治疗组之间没有差异。与氢氯噻嗪相比，接受伊拉地平治疗的患者血管事件发生率增加令人担忧，应进一步研究。
