Koutishenko N, Metelitsa V I
National Research Centre for Preventive Medicine of Russia, Moscow.
Int J Cardiol. 1998 Apr 1;64(2):137-44. doi: 10.1016/s0167-5273(98)00020-5.
We compared the effects of abrupt cessation of nifedipine and isosorbide dinitrate therapy in patients with stable angina pectoris. Eighteen males were studied. Each patient received isosorbide dinitrate and nifedipine continuously for 5 weeks by randomised cross-over technique. Exercise treadmill tests were performed before each treatment period, at the beginning of treatment, 4 weeks after initiation of treatment and on the first and eighth days of drug withdrawal. At the end of treatment the antianginal effect of both agents attenuated (versus acute administration). Abrupt cessation of isosorbide dinitrate caused only a tendency towards decrease in exercise tolerance versus pre-treatment level. Alternatively, abrupt cessation of nifedipine resulted in substantial deterioration in exercise tolerance, which was statistically significant 21 and 24 h after the last dose administration. The number of anginal attacks increased >25% in two patients after cessation of isosorbide dinitrate and in eight patients after cessation of nifedipine. In no patient rest angina episodes appeared after stopping of isosorbide dinitrate, however, after stopping of nifedipine rest angina episodes appeared in three patients. We conclude that withdrawal phenomenon of nifedipine is much more pronounced than that of isosorbide dinitrate and may emerge on the first day of drug cessation. Such a phenomenon may be evident even in patients in whom nifedipine effect have attenuated due to the development of tolerance.
我们比较了硝苯地平与硝酸异山梨酯突然停药对稳定型心绞痛患者的影响。对18名男性患者进行了研究。采用随机交叉技术，让每位患者连续5周服用硝酸异山梨酯和硝苯地平。在每个治疗期之前、治疗开始时、治疗开始后4周以及停药的第1天和第8天进行运动平板试验。治疗结束时，两种药物的抗心绞痛作用均减弱（与急性给药相比）。硝酸异山梨酯突然停药仅使运动耐量有较治疗前水平下降的趋势。相反，硝苯地平突然停药导致运动耐量显著恶化，在最后一剂给药后21小时和24小时具有统计学意义。硝酸异山梨酯停药后，2例患者心绞痛发作次数增加>25%；硝苯地平停药后，8例患者心绞痛发作次数增加>25%。硝酸异山梨酯停药后，无患者出现静息性心绞痛发作；然而，硝苯地平停药后，3例患者出现静息性心绞痛发作。我们得出结论，硝苯地平的撤药现象比硝酸异山梨酯更为明显，且可能在停药第一天就出现。即使在因耐受性发展而硝苯地平作用已减弱的患者中，这种现象也可能很明显。
