Lipicky R J
Division of Cardio-Renal Drug Products, U.S. Food and Drug Administration, Rockville, Maryland 20857.
Am J Cardiol. 1993 Aug 26;72(6):53B-54B. doi: 10.1016/0002-9149(93)90042-b.
Insufficient evidence exists to suggest that prolongation of the QT interval corrected for heart rate (QTc) is necessarily beneficial. In all but life-threatening situations, QTc prolongation resulting from pharmacologic agents must be considered a risk. Because dose-response relations for torsades de pointes cannot be established and because prolongation of the QTc interval is thought to precede the development of torsades, it is reasonable to assume that the QTc prolongation itself constitutes the marker of risk. An assessment of the relation between the dose of a given drug and its effect on the QTc interval will aid in making the judgment that the potential benefit outweighs the risk. Ideally, a drug should demonstrate as wide a safety margin as possible, as reflected in a large separation between the ED50 value associated with therapeutic benefit and that associated with QTc prolongation.
现有证据不足表明校正心率后的QT间期（QTc）延长必然有益。除危及生命的情况外，药物导致的QTc延长必须被视为一种风险。由于无法建立尖端扭转型室速的剂量反应关系，且认为QTc间期延长先于尖端扭转型室速的发生，因此有理由认为QTc延长本身就是风险标志。评估特定药物剂量与其对QTc间期的影响之间的关系，将有助于判断潜在益处是否大于风险。理想情况下，药物应显示出尽可能宽的安全范围，这体现在与治疗益处相关的ED50值和与QTc延长相关的ED50值之间有很大差距。
