Göbel E J, Hautvast R W, van Gilst W H, Spanjaard J N, Hillege H L, DeJongste M J, Molhoek G P, Lie K I
Department of Cardiology, University Hospital Groningen,The Netherlands.
Lancet. 1995;346(8991-8992):1653-7. doi: 10.1016/s0140-6736(95)92837-5.
The effect of dihydropyridines in patients with unstable angina is discouraging. To find out the effect of the non-dihydropyridine-like calcium-channel blocker diltiazem, a randomised, double-blind trial was conducted comparing diltiazem with glyceryl trinitrate, both given intravenously, in 129 patients with unstable angina. The endpoints were refractory angina or myocardial infarction, individually and as a composite endpoint. Refractory angina alone or together with myocardial infarction occurred significantly less commonly in the diltiazem group. While patients were on the trial drugs the numbers with refractory angina were 6 (10%) in the diltiazem group versus 17 (28%) in the glyceryl trinitrate group (relative risk 0.36, p = 0.02), and the numbers with refractory angina and myocardial infarction were 9 (15%) versus 23 (38%) (relative risk 0.40, p = 0.007). Over 48 h the number were: refractory angina 8 (13%) versus 18 (30%), relative risk 0.45, p = 0.03, and refractory angina and myocardial infarction 12 (20.0%) versus 25 (41%), relative risk 0.49, p = 0.02. Patients in the diltiazem group had better (p < 0.05) event-free survival while taking the drugs. Heart-rate pressure product was reduced significantly only by diltiazem (p < 0.05). The incidence of bradyarrhythmias did not differ significantly. Atrioventricular conduction disturbances occurred in 5 (8%) patients in the diltiazem group but were not seen in the glyceryl trinitrate group (p = 0.03). These disturbances could be reversed by decreasing the dose of the drug or withdrawing it. No temporary pacemakers were required. Headache requiring an analgesic or dose adjustment occurred significantly less in the diltiazem group: 3 (5%) versus 15 (25%), relative risk 0.20 (p < 0.004). These results indicate that intravenous diltiazem, compared with intravenous glyceryl trinitrate, significantly reduces ischaemic events and can be used safely in patients with unstable angina.
二氢吡啶类药物对不稳定型心绞痛患者的疗效令人沮丧。为了探究非二氢吡啶类钙通道阻滞剂地尔硫䓬的疗效，对129例不稳定型心绞痛患者进行了一项随机双盲试验，比较静脉注射地尔硫䓬和硝酸甘油的效果。终点指标为难治性心绞痛或心肌梗死，包括单独发生的情况以及作为复合终点。单独或合并心肌梗死的难治性心绞痛在地尔硫䓬组中发生的频率显著更低。在患者服用试验药物期间，地尔硫䓬组中难治性心绞痛患者有6例（10%），而硝酸甘油组有17例（28%）（相对风险0.36，p = 0.02）；难治性心绞痛合并心肌梗死的患者分别为9例（15%）和23例（38%）（相对风险0.40，p = 0.007）。在48小时内，数据如下：难治性心绞痛患者分别为8例（13%）和18例（30%），相对风险0.45，p = 0.03；难治性心绞痛合并心肌梗死的患者分别为12例（20.0%）和25例（41%），相对风险0.49，p = 0.02。地尔硫䓬组患者在服药期间无事件生存率更高（p < 0.05）。仅地尔硫䓬能显著降低心率血压乘积（p < 0.05）。缓慢性心律失常的发生率无显著差异。地尔硫䓬组有5例（8%）患者发生房室传导障碍，而硝酸甘油组未观察到（p = 0.03）。这些障碍可通过减少药物剂量或停药得以逆转。无需临时起搏器。地尔硫䓬组中需要使用镇痛药或调整剂量的头痛发生率显著更低：3例（5%）对比15例（25%），相对风险0.20（p < 0.004）。这些结果表明，与静脉注射硝酸甘油相比，静脉注射地尔硫䓬可显著减少缺血事件，且可安全用于不稳定型心绞痛患者。
