Théroux P, Baird M, Juneau M, Warnica W, Klinke P, Kostuk W, Pflugfelder P, Lavallée E, Chin C, Dempsey E
Canadian Multicenter Diltiazem Study Group, Montreal.
Circulation. 1991 Jul;84(1):15-22. doi: 10.1161/01.cir.84.1.15.
Silent myocardial ischemia is an adverse prognostic marker in patients with coronary disease; however, controlled data on the effect of treatment are sparse and contradictory, and the relations among the occurrence of ST segment depression, drug efficacy, and heart rate are unclear.
Sixty patients with stable coronary artery disease, a positive treadmill exercise test and asymptomatic ST segment depression on ambulatory electrocardiographic recording were assessed in a multicenter, double-blind, placebo-controlled, cross-over trial. Treadmill exercise tests and 72-hour electrocardiographic recordings were obtained at the end of two 2-week treatment periods with sustained-release diltiazem 180 mg b.i.d. or equivalent placebo. Episodes of asymptomatic ST depression decreased by 50% or more in 70% of the patients from a median number of 4.5 (range, 0-19) to 1.5 (range, 0-13) (p = 0.0001); their cumulative duration also decreased from 78.5 (range, 0-60) to 24.5 (range, 0-411) minutes (p = 0.001). No circadian variation was found in the efficacy of diltiazem. The occurrence of ischemic type ST segment depression was modulated by changes in heart rate rather than by absolute heart rate. Diltiazem also improved exercise test end points but to a lesser extent. Time to ST segment depression increased to 341 +/- 148 from 296 +/- 154 seconds (p = 0.005). Although less frequent with diltiazem administration (45 versus 54 patients, p less than 0.03), exercise-induced ST depression was more often asymptomatic (98% versus 72% of patients, p less than 0.0001).
Diltiazem reduces the frequency and severity of ischemic type ST depression in patients with stable coronary artery disease.
无症状性心肌缺血是冠心病患者不良的预后指标;然而,关于治疗效果的对照数据稀少且相互矛盾,ST段压低的发生、药物疗效和心率之间的关系尚不清楚。
在一项多中心、双盲、安慰剂对照、交叉试验中,对60例稳定型冠心病患者进行评估,这些患者平板运动试验阳性且动态心电图记录显示无症状性ST段压低。在两个为期2周的治疗期结束时,分别给予缓释地尔硫䓬180mg,每日两次或等效安慰剂,然后进行平板运动试验和72小时心电图记录。70%的患者无症状性ST段压低发作次数减少了50%或更多,从中位数4.5次(范围0 - 19次)降至1.5次(范围0 - 13次)(p = 0.0001);其累积持续时间也从78.5分钟(范围0 - 60分钟)降至24.5分钟(范围0 - 411分钟)(p = 0.001)。未发现地尔硫䓬疗效存在昼夜变化。缺血型ST段压低的发生受心率变化而非绝对心率的调节。地尔硫䓬还改善了运动试验终点,但程度较小。ST段压低出现的时间从296±154秒增加到341±148秒(p = 0.005)。虽然使用地尔硫䓬时运动诱发的ST段压低较少见(45例对54例患者,p < 0.03),但更常为无症状性(98%对72%的患者,p < 0.0001)。
地尔硫䓬可降低稳定型冠心病患者缺血型ST段压低的频率和严重程度。