Harston W E, Friesinger G C
Am Heart J. 1982 Aug;104(2 Pt 2):504-11. doi: 10.1016/0002-8703(82)90147-8.
Twelve patients with documented coronary arteriosclerosis and severe stable angina pectoris were treated with the beta blocker pindolol, 5 mg four times a day, utilizing a double-blind crossover protocol. Following 4 weeks of baseline observation with no active treatment, pindolol and placebo were given for 4 weeks each. End points evaluated were episodes of angina pectoris/week, number of nitroglycerin tablets used per week, time on treadmill test until onset of angina pectoris, double product of heart rate and blood pressure at onset of angina pectoris, and amount of ST depression during the treadmill exercise test. Episodes of angina pectoris and nitroglycerin consumption were reduced by 18% on placebo and 32% on pindolol (not significant). All of the improvement occurred in the third and fourth weeks of pindolol treatment. Less difference between pindolol and placebo was noted when the placebo period came after the pindolol period, suggesting a carry-over effect of pindolol. With pindolol, treatment exercise tolerance was increased 13% (33 seconds) over baseline levels but only 2% over the levels achieved with placebo treatment (not significant). ST depression with exercise was 6% less when patients were on pindolol than when they were on placebo (not significant). There was a marked decrease in myocardial oxygen demand as measured by the double product of blood pressure and pulse during exercise (23% reduction when on pindolol and no change when on placebo, p less than 0.01). This study shows that there was an important placebo effect when treatment of angina pectoris was evaluated and that pindolol significantly reduced myocardial oxygen demand but evidence of ischemia was not significantly reduced. Possible mechanisms to explain the disparity between reduction in estimated myocardial oxygen demand (double product) and objective improvement in ischemia include coronary spasm and altered regional flow resulting from beta blockade. Alternative explanations may be the relatively small fixed dose of pindolol and the small number of patients studied.
12名有冠状动脉硬化和严重稳定型心绞痛记录的患者,采用双盲交叉方案,接受β受体阻滞剂吲哚洛尔治疗,每天4次,每次5毫克。在无积极治疗的4周基线观察期后,吲哚洛尔和安慰剂各服用4周。评估的终点指标包括每周心绞痛发作次数、每周使用硝酸甘油片的数量、跑步机测试中直至心绞痛发作的时间、心绞痛发作时心率与血压的乘积、跑步机运动测试期间ST段压低的程度。安慰剂组心绞痛发作次数和硝酸甘油消耗量减少了18%,吲哚洛尔组减少了32%(无统计学意义)。所有改善均出现在吲哚洛尔治疗的第三和第四周。当安慰剂期在吲哚洛尔期之后时,吲哚洛尔与安慰剂之间的差异较小,提示吲哚洛尔有残留效应。使用吲哚洛尔时,治疗运动耐量比基线水平提高了13%(33秒),但仅比安慰剂治疗所达到的水平提高了2%(无统计学意义)。患者服用吲哚洛尔时运动时的ST段压低比服用安慰剂时少6%(无统计学意义)。运动期间通过血压与脉搏乘积测量的心肌需氧量显著降低(服用吲哚洛尔时降低23%,服用安慰剂时无变化,P<0.01)。本研究表明,在评估心绞痛治疗时存在重要的安慰剂效应,吲哚洛尔可显著降低心肌需氧量,但缺血证据未显著减少。解释估计的心肌需氧量(乘积)降低与缺血客观改善之间差异的可能机制包括冠状动脉痉挛和β受体阻滞导致的局部血流改变。其他解释可能是吲哚洛尔的固定剂量相对较小以及研究的患者数量较少。