Schneeweiss A, Reisin L, Marmor A, Caspi A
Cardiovascular Research Foundation, Bad Schwalbach, Germany.
Cardiology. 1994;84 Suppl 1:4-12. doi: 10.1159/000176439.
214 patients with angina pectoris were randomized to placebo or isosorbide-5-mononitrate (ISMN) rapid release 5, 10 or 20 mg b.i.d. at 8 a.m. and 3 p.m. Exercise tests were performed between 8 a.m. and 10 p.m., before and 2 and 7 h after each dose on days 2 and 14 and before and 2 h after the morning dose on days 7 and 21. All doses of ISMN increased exercise duration significantly more than placebo, and this effect lasted throughout most of the day. It was maximal (73 s; 24%) 2 h after the morning dose, slightly attenuated but still significant at 7 h, increased 2 h after the second dose and attenuated but still greater than with placebo at 7 h. The increase was even greater at 3 weeks (99 s; 29%), perhaps due to a training effect. Similar improvement was observed in other exercise parameters. There was no significant dose response. There were 100% more anginal attacks in the placebo than in the 20-mg treatment group. No rebound (assessed by comparing exercise duration before the morning dose between the groups) was observed.
ISMN b.i.d. eccentrically has an antianginal effect throughout most of the day, peaking at 2 h. This effect is sustained during chronic therapy, without tolerance or rebound.
214例心绞痛患者被随机分为安慰剂组或接受5、10或20毫克5-单硝酸异山梨酯（ISMN）速释剂治疗，每日两次，分别于上午8点和下午3点服用。在第2天和第14天，以及第7天和第21天，于上午8点至晚上10点之间，在每次给药前、给药后2小时和7小时进行运动试验，并在上午给药前和给药后2小时进行运动试验。所有剂量的ISMN均使运动持续时间显著增加，且此效应持续一整天的大部分时间。上午给药后2小时效应最大（增加73秒；24%），7小时时略有减弱但仍显著，第二次给药后2小时增加，7小时时减弱但仍大于安慰剂组。3周时增加更为明显（增加99秒；29%），可能是由于训练效应。在其他运动参数方面也观察到类似改善。未观察到显著的剂量反应。安慰剂组的心绞痛发作次数比20毫克治疗组多100%。未观察到反跳现象（通过比较两组上午给药前的运动持续时间进行评估）。
每日两次偏心给药的ISMN在一天的大部分时间都有抗心绞痛作用，在2小时时达到峰值。在长期治疗期间，这种效应持续存在，无耐受性或反跳现象。
