Mitrovic V, Miskovic A, Straub M, Beckmann K, Thormann J, Pitschner H
Kerckhoff-Klinik GmbH, Benekestr. 2-8, D-61231 Bad Nauheim.
Z Kardiol. 1999 Oct;88(10):838-49. doi: 10.1007/s003920050360.
Clinical drawbacks of beta-blocker treatment in stable angina have motivated researchers to provide alternative heart rat lowering agents, such as tedisamil which additionally exerts anti-ischemic and antiarrhythmic effects by blockade of cellular repolarizing K(+) currents.
48 patients with stable angina pectoris were investigated (double-blind, randomized, parallel grouped) comparing the hemodynamic, anti-ischemic, metabolic and neurohumoral effects of tedisamil 100 mg b.i.d and atenolol 50 mg b.i.d. after a single dose and over 6 days of treatment. Tedisamil and atenolol produced a decrease in heart rate both at rest (day 1: -13.6 vs -15.4 bpm; p > 0.05; day 6: -14.8 vs -22.2 bpm; resp.; p > 0.05) and exercise (day 1: -9.1 vs -18.3 bpm; p = 0. 001; day 6: -12.0 vs -24.8 bpm, resp.; p = 0.001), while anginal threshold increased. Cardiac output decreased with tedisamil and atenolol at rest (day 1: -1.01 vs -1.19 l/min; p > 0.05; day 6: -0. 86 vs -1.10 l/min, resp.; p > 0.05) and exercise (day 1: -0.82 vs -1. 28 l/min; p > 0.05; day 6: -0.65 vs -2.68 l/min, resp.; p = 0.03), while stroke volume remained unchanged. Right atrial pressure changed during exercise only: It decreased with tedisamil (-1.7 mm Hg) and increased with atenolol (+3.7 mm Hg). Mean pulmonary capillary wedge pressures decreased at rest (-0.5 mm Hg) and exercise (-6.9 mm Hg) in the tedisamil group, but tended to increase with atenolol on day 6 (rest: +1.7; exercise: +3.7 mm Hg) (p = 0.03). Arterial pressure decreased under atenolol treatment only. Exercise-induced plasma norepinephrine levels were reduced by tedisamil (-93 pg/ml) but elevated by atenolol (+172 pg/ml) (p = 0. 001). As compared to atenolol, tedisamil produced a significant prolongation of QT (c) interval (+31 vs -8 ms) (p = 0.002) at initial values of 0.408 +/- 0.018 s with PQ and QRS remaining unaltered.
In the present study, tedisamil (100 mg b.i.d. ) generated favorable hemodynamic, neurohumoral and anti-ischemic effects in patients with stable angina pectoris. The anti-ischemic efficacy of tedisamil, as measured by ST segment depression and angina threshold, is comparable to that of atenolol (50 mg b.i.d.).
β受体阻滞剂治疗稳定型心绞痛存在临床缺陷，促使研究人员寻找替代的心率降低药物，如替地沙米，它还可通过阻断细胞复极化钾离子电流发挥抗缺血和抗心律失常作用。
对48例稳定型心绞痛患者进行了研究（双盲、随机、平行分组），比较了单次给药后及治疗6天期间，替地沙米100mg每日两次和阿替洛尔50mg每日两次的血流动力学、抗缺血、代谢及神经体液效应。替地沙米和阿替洛尔在静息时（第1天：-13.6对-15.4次/分；p>0.05；第6天：-14.8对-22.2次/分；分别为；p>0.05）和运动时（第1天：-9.1对-18.3次/分；p = 0.001；第6天：-12.0对-24.8次/分；分别为；p = 0.001）均使心率降低，同时心绞痛阈值升高。静息时替地沙米和阿替洛尔均使心输出量降低（第1天：-1.01对-1.19升/分；p>0.05；第6天：-0.86对-1.10升/分；分别为；p>0.05），运动时也降低（第1天：-0.82对-1.28升/分；p>0.05；第6天：-0.65对-2.68升/分；分别为；p = 0.03），而每搏输出量保持不变。仅在运动时右心房压发生变化：替地沙米使其降低（-1.7mmHg），阿替洛尔使其升高（+3.7mmHg）。替地沙米组静息时（-0.5mmHg）和运动时（-6.9mmHg）平均肺毛细血管楔压降低，但在第6天阿替洛尔使其有升高趋势（静息时：+1.7；运动时：+3.7mmHg）（p = 0.03）。仅在阿替洛尔治疗时动脉压降低。替地沙米使运动诱导的血浆去甲肾上腺素水平降低（-93pg/ml），而阿替洛尔使其升高（+172pg/ml）（p = 0.001）。与阿替洛尔相比，替地沙米在初始值为0.408±0.018秒时使QT（c）间期显著延长（+31对-8毫秒）（p = 0.002），PQ和QRS保持不变。
在本研究中，替地沙米（100mg每日两次）在稳定型心绞痛患者中产生了良好的血流动力学、神经体液及抗缺血效应。以ST段压低和心绞痛阈值衡量，替地沙米的抗缺血疗效与阿替洛尔（50mg每日两次）相当。
