Kloner R A, Vetrovec G W, Materson B J, Levenstein M
Heart Institute, Good Samaritan Hospital and the University of Southern California, Los Angeles 90017, USA.
Am J Cardiol. 1998 Jan 15;81(2):163-9. doi: 10.1016/s0002-9149(97)00868-0.
Issues raised recently concerning the safety of calcium channel blockers (CCBs) prompted an analysis of the occurrence of cardiovascular events and death in the Pfizer Inc. hypertension clinical trial databases for amlodipine (Norvasc) and nifedipine in the gastrointestinal therapeutic system (GITS) formulation (Procardia XL). Prospectively defined analyses of data from comparative and noncomparative trials of amlodipine and nifedipine GITS were conducted. Outcome measures included cardiovascular and noncardiovascular deaths, and adverse cardiovascular events including new/worsened angina, myocardial infarction (MI), serious arrhythmia, stroke, congestive heart failure, and bleeding. Among all amlodipine-treated patients (n = 32,920), the incidence rates for all-cause death, MI, and new/worsened angina were 3.0, 3.3, and 1.6/1,000 patient-years of exposure, respectively. Among those in comparative trials alone (n = 4,126), the all-cause death rate was 4.1/1,000 patient-years, which was comparable to that of other non-CCB agents and significantly less than that of other CCBs (23.8/1,000 patient-years, p = 0.015), although the difference in rates represents only 2 deaths. Among all nifedipine-GITS-treated patients (n = 2,645), the rate of all-cause death was 4.1/1,000 patient-years, of MI 6.5/1,000 patient-years, and of new/ worsened angina 5.7/1,000 patient-years. The incidence rates for MI and other cardiac events were low in these hypertension trials, and did not differ among treatment groups in either the amlodipine or nifedipine GITS comparative analyses. In the clinical trial databases analyzed, there is no signal suggesting excessive risk of death or cardiovascular events for hypertensive patients treated with amlodipine or nifedipine GITS.
近期有关钙通道阻滞剂（CCB）安全性的问题，促使人们对辉瑞公司氨氯地平（络活喜）和硝苯地平胃肠道治疗系统（GITS）制剂（拜新同）的高血压临床试验数据库中心血管事件及死亡的发生情况进行分析。对氨氯地平和硝苯地平GITS的对比试验及非对比试验数据进行了前瞻性定义分析。观察指标包括心血管和非心血管死亡，以及不良心血管事件，如新发/加重型心绞痛、心肌梗死（MI）、严重心律失常、中风、充血性心力衰竭和出血。在所有接受氨氯地平治疗的患者（n = 32,920）中，全因死亡、MI和新发/加重型心绞痛的发生率分别为每1000患者年暴露3.0、3.3和1.6例。仅在对比试验中的患者（n = 4,126）中，全因死亡率为每1000患者年4.1例，这与其他非CCB药物相当，且显著低于其他CCB药物（每1000患者年23.8例，p = 0.015），尽管发生率差异仅代表2例死亡。在所有接受硝苯地平GITS治疗的患者（n = 2,645）中，全因死亡率为每1000患者年4.1例，MI为每1000患者年6.5例，新发/加重型心绞痛为每1000患者年5.7例。在这些高血压试验中，MI和其他心脏事件的发生率较低，在氨氯地平或硝苯地平GITS对比分析中，各治疗组之间无差异。在所分析的临床试验数据库中，没有迹象表明接受氨氯地平或硝苯地平GITS治疗的高血压患者存在过高的死亡或心血管事件风险。
