Starling M R, Crawford M H, O'Rourke R A
Int J Cardiol. 1982;1(3-4):229-37. doi: 10.1016/0167-5273(82)90083-3.
We evaluated a new slow-channel calcium-blocking agent, diltiazem hydrochloride, in 10 patients with documented fixed coronary artery disease who had reproducible angina and greater than or equal to 0.1 mV ST segment depression on ECG treadmill exercise testing after 1 week of single-blind placebo administration. Subsequently, over the next 6 weeks, either diltiazem (30 mg/tablet) or placebo were administered for 1 week each in a randomized double-blind triple crossover design, as one tablet four times a day, two tablets three times a day or two tablets four times a day, for a total diltiazem dose of 120, 180 and 240 mg/day, respectively. Treadmill (electrocardiogram) exercise testing was performed at the end of each week. Only diltiazem at 240 mg/day increased significantly the time to angina pectoris (P less than 0.05), time to ST segment depression (P = 0.01), time to maximal exercise (P less than 0.02), and heart rate at maximal exercise (P less than 0.05) without effecting significantly the maximal rate-pressure product compared to the corresponding placebo values. In addition, using only the diltiazem data, a significant high dose response was observed for time to angina (P less than 0.05), ST segment depression (P less than 0.005), and maximal exercise (P less than 0.025). No adverse reactions were reported during the study. Therefore, we conclude that 240 mg/day of diltiazem improves significantly exercise performance in patients with angina pectoris due to fixed coronary artery disease and adverse effects, rarely, if ever, occur at this dosage.
我们对一种新型慢通道钙阻滞剂盐酸地尔硫䓬进行了评估,研究对象为10例确诊为固定性冠状动脉疾病的患者,这些患者有可重复性心绞痛,且在单盲安慰剂给药1周后,心电图平板运动试验显示ST段压低≥0.1mV。随后,在接下来的6周内,采用随机双盲三交叉设计,给予地尔硫䓬(30mg/片)或安慰剂,每种药物各服用1周,服用方式为每日4次,每次1片;或每日3次,每次2片;或每日4次,每次2片,地尔硫䓬的总剂量分别为每日120mg、180mg和240mg。每周结束时进行平板(心电图)运动试验。与相应的安慰剂值相比,仅每日240mg的地尔硫䓬能显著延长心绞痛发作时间(P<0.05)、ST段压低时间(P = 0.01)、最大运动时间(P<0.02)以及最大运动时的心率(P<0.05),而对最大心率血压乘积无显著影响。此外,仅根据地尔硫䓬的数据,观察到在心绞痛发作时间(P<0.05)、ST段压低时间(P<0.005)和最大运动时间(P<0.025)方面存在显著的高剂量反应。研究期间未报告不良反应。因此,我们得出结论,每日240mg的地尔硫䓬可显著改善因固定性冠状动脉疾病导致心绞痛患者的运动能力,且该剂量极少出现不良反应。