Thadani U, Maranda C R, Amsterdam E, Spaccavento L, Friedman R G, Chernoff R, Zellner S, Gorwit J, Hinderaker P H
Cardiology Section, University of Oklahoma Health Sciences Center, Oklahoma City 73104.
Ann Intern Med. 1994 Mar 1;120(5):353-9. doi: 10.7326/0003-4819-120-5-199403010-00001.
To determine whether isosorbide-5-mononitrate (IS-5-MN), an active metabolite of isosorbide dinitrate, when given twice daily (in the morning and 7 hours later), prevents development of tolerance and reduction in exercise performance or is associated with a rebound increase in anginal attacks in patients with stable angina pectoris.
Multicenter, placebo-controlled, parallel-group, double-blind, randomized study.
Four university teaching hospitals and five private cardiology outpatient clinics.
116 patients with stable exertional angina who stopped treadmill exercise because of angina pectoris.
After stopping all antianginal drugs with the exception of beta-blockers, patients received single-blind placebo for 1 week followed by either 20 mg of IS-5-MN (n = 60 patients) or placebo (n = 62 patients) twice daily at 0800 hours and 1500 hours for 2 weeks.
Serial symptom-limited exercise tests and patients' diaries recording activity and date, time, and severity of anginal attacks.
Compared with placebo recipients, patients receiving IS-5-MN walked significantly longer at 2, 5, and 7 hours after the 0800-hour dose (P < 0.01) and at 2 and 5 hours after the 1500-hour dose (P < 0.01). Before the morning (0800-hour) dose, exercise duration increased by 0.53 minutes in placebo recipients and by 0.85 minutes in those receiving IS-5-MN therapy (P = 0.10). Neither nocturnal nor early-morning anginal attacks increased during IS-5-MN therapy compared with placebo. Headaches occurred in 19 (32%) patients in the IS-5-MN group and in 9 (15%) patients in the placebo group but necessitated discontinuation of treatment in only 2 (3%) patients in the IS-5-MN group.
Isosorbide-5-mononitrate, 20 mg twice daily given 7 hours apart, was well tolerated and improved exercise performance for 7 hours after the morning dose and for 5 hours after the afternoon dose without evidence of development of pharmacologic tolerance. No rebound increase in anginal attacks was found.
确定硝酸异山梨酯的活性代谢产物5-单硝酸异山梨酯（IS-5-MN）每日两次（早晨及7小时后）给药时，能否预防稳定性心绞痛患者耐受性的产生及运动能力下降，或是否会导致心绞痛发作次数反跳性增加。
多中心、安慰剂对照、平行组、双盲、随机研究。
4所大学教学医院和5所私立心脏病门诊诊所。
116例因心绞痛而停止跑步机运动的稳定性劳力性心绞痛患者。
除β受体阻滞剂外，停用所有抗心绞痛药物后，患者接受单盲安慰剂治疗1周，随后分别于08:00和15:00每日两次给予20 mg IS-5-MN（n = 60例患者）或安慰剂（n = 62例患者），持续2周。
连续进行症状限制运动试验，患者记录活动情况以及心绞痛发作的日期、时间和严重程度。
与接受安慰剂的患者相比，接受IS-5-MN治疗的患者在08:00剂量后的2、5和7小时以及15:00剂量后的2和5小时步行时间显著延长（P < 0.01）。早晨（08:00）剂量前，接受安慰剂的患者运动持续时间增加0.53分钟，接受IS-5-MN治疗的患者增加0.85分钟（P = 0.10）。与安慰剂相比，IS-5-MN治疗期间夜间及清晨心绞痛发作次数均未增加。IS-5-MN组19例（32%）患者出现头痛，安慰剂组9例（15%）患者出现头痛，但IS-5-MN组仅2例（3%）患者因头痛而停药。
5-单硝酸异山梨酯每日两次，每次20 mg，间隔7小时给药，耐受性良好，早晨给药后7小时及下午给药后5小时运动能力得到改善，且无药理学耐受性产生的证据。未发现心绞痛发作次数反跳性增加。
