Sussex B A, Campbell N R, Raju M K, McKay D W
Health Science Centre, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Clin Pharmacol Ther. 1994 Aug;56(2):229-34. doi: 10.1038/clpt.1994.128.
To determine whether the use of a diuretic would maintain the antianginal efficacy of isosorbide dinitrate during 1 week of therapy.
During continuous therapy, organic nitrates have a reduction in antianginal effectiveness and cause fluid retention. The study was a randomized, double-blind, placebo-controlled crossover design examining the effect of 1 week of daily treatment with 50 mg hydrochlorothiazide/5 mg amiloride on the antianginal effectiveness of 30 mg isosorbide dinitrate administered every 6 hours. Exercise stress testing was performed before and 3 hours after administration of isosorbide dinitrate at the start and end of the placebo and diuretic treatment phases.
The time to onset of angina (475 +/- 35 versus 490 +/- 29 seconds, difference not significant) and to moderate angina after administration of isosorbide dinitrate (542 +/- 40 versus 566 +/- 37 seconds, difference not significant) were similar at the start and end of the diuretic phase of the study but were reduced at the end of the placebo phase (471 +/- 40 versus 410 +/- 40 seconds, p < 0.05 and 531 +/- 38 versus 466 +/- 39 seconds, p < 0.05, respectively). Total exercise time and time to onset of angina 3 hours after administration of isosorbide dinitrate were longer (p < 0.005) at the end of the diuretic phase compared with the end of the placebo phase. Patients gained weight during the placebo phase and lost weight during the diuretic phase of the study. The change in weight was inversely correlated to the change in total exercise time (r = -0.53, p < 0.05).
Patients using a diuretic with isosorbide dinitrate maintain an increased anginal threshold and total exercise time compared with placebo. Weight change is inversely related to exercise duration, and this result is consistent with fluid retention restoring cardiac preload during nitrate use. The increased anginal threshold during concurrent isosorbide dinitrate and diuretic use may be attributable to maintenance of the organic nitrate-induced reductions in cardiac preload.
确定在1周的治疗期间使用利尿剂是否能维持硝酸异山梨酯的抗心绞痛疗效。
在持续治疗期间，有机硝酸盐的抗心绞痛效果会降低并导致液体潴留。该研究采用随机、双盲、安慰剂对照交叉设计，考察每日服用50mg氢氯噻嗪/5mg阿米洛利1周对每6小时服用30mg硝酸异山梨酯的抗心绞痛效果的影响。在安慰剂和利尿剂治疗阶段开始和结束时，于服用硝酸异山梨酯前及服用后3小时进行运动应激试验。
在研究的利尿剂阶段开始和结束时，心绞痛发作时间（475±35秒对490±29秒，差异不显著）以及服用硝酸异山梨酯后中度心绞痛发作时间（542±40秒对566±37秒，差异不显著）相似，但在安慰剂阶段结束时缩短（分别为471±40秒对410±40秒，p<0.05；531±38秒对466±39秒，p<0.05）。与安慰剂阶段结束时相比，利尿剂阶段结束时的总运动时间以及服用硝酸异山梨酯后3小时的心绞痛发作时间更长（p<0.005）。在研究的安慰剂阶段患者体重增加，而在利尿剂阶段体重减轻。体重变化与总运动时间变化呈负相关（r=-0.53，p<0.05）。
与安慰剂相比，联用利尿剂和硝酸异山梨酯的患者心绞痛阈值提高，总运动时间增加。体重变化与运动持续时间呈负相关，这一结果与使用硝酸盐期间液体潴留恢复心脏前负荷一致。同时使用硝酸异山梨酯和利尿剂期间心绞痛阈值升高可能归因于有机硝酸盐诱导的心脏前负荷降低得以维持。
