EFFICACY AND SAFETY OF EXTENDED-RELEASE ISOSORBIDE-MONONITRATE FOR STABLE EFFORT ANGINA-PECTORIS
EFFICACY AND SAFETY OF EXTENDED-RELEASE ISOSORBIDE-MONONITRATE FOR STABLE EFFORT ANGINA-PECTORIS
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DOI：
10.1016/0002-9149(93)90292-k
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发表时间：
1993-12-01
影响因子：
2.8
通讯作者：
CASARETO, R
中科院分区：
文献类型：
--
作者：
CHRYSANT, SG;GLASSER, SP;CASARETO, R
评价单硝酸异山梨酯缓释片治疗稳定型劳力型心绞痛的疗效和安全性。在一项双盲研究中，313例稳定型心绞痛患者随机接受安慰剂或缓释单硝酸异山梨酯：30、60、120或240 mg，每日早晨一次。在第1、7、14、28和42天早晨给药前即刻和给药后4和12小时，使用标准布鲁斯跑步机方案进行系列运动试验。初始给药后，与安慰剂组相比，所有接受单硝酸异山梨酯缓释剂的组在给药后4和12小时的平均总运动时间显著增加（p < 0.01），约为30至50秒。在第42天，接受120或240 mg单硝酸异山梨酯缓释剂的患者在给药后4小时总运动时间较基线的平均变化超过安慰剂约50至60秒（p < 0.01），在给药后12小时超过30至35秒（p小于或等于0.05）。在给药后24小时，对缓释单硝酸异山梨酯和安慰剂的反应之间没有检测到显著差异（即，在下一次给药前）。因此，在给药间隔结束时，既没有显著的活动，也没有明显的努力诱导的心绞痛反弹（零时效应）。短暂性头痛是最常见的不良反应。缓释单硝酸异山梨酯（120和240 mg，每日一次口服给药）在长期治疗期间显著延长了给药后4和12小时至发生中度用力诱导型心绞痛的运动时间，而没有发生硝酸盐耐受性。该药物耐受性良好，未观察到努力诱导的心绞痛的零时反弹。
The efficacy and safety of extended-release isosorbide mononitrate tablets were evaluated in patients with stable effort angina. In a double-blind study, 313 patients with stable effort-induced angina were randomized to receive placebo or extended-release isosorbide mononitrate: 30, 60, 120 or 240 mg once daily in the morning. Serial exercise testing was performed using the standard Bruce treadmill protocol on days 1, 7, 14, 28 and 42 immediately before morning drug administration and 4 and 12 hours after administration. After initial dosing, all groups that received extended-release isosorbide mononitrate had significant (p < 0.01) increases in mean total exercise time of approximately 30 to 50 seconds in relation to placebo 4 and 12 hours after administration. On day 42, mean changes from baseline in total exercise time of patients who received 120 or 240 mg of extended-release isosorbide mononitrate exceeded placebo by approximately 50 to 60 seconds 4 hours after dosing (p < 0.01), and by 30 to 35 seconds 12 hours after dosing (p less-than-or-equal-to 0.05). No significant difference was detected between responses to extended-release isosorbide mononitrate and placebo 24 hours after administration (i.e., immediately before the next dose). Thus, there was neither significant activity nor demonstrable rebound of effort-induced angina (zero-hour effect) at the end of the dosing interval. Transient headache was the most prevalent adverse experience. Extended-release isosorbide mononitrate (120 and 240 mg administered orally once daily) significantly prolonged exercise time to development of moderate effort-induced angina 4 and 12 hours after dosing during long-term therapy, without development of nitrate tolerance. The drug was well tolerated, and no zero-hour rebound of effort-induced angina was observed.