Makkar R R, Fromm B S, Steinman R T, Meissner M D, Lehmann M H
Department of Internal Medicine, Wayne State University/Harper Hospital, Detroit, Mich.
JAMA. 1993 Dec 1;270(21):2590-7. doi: 10.1001/jama.270.21.2590.
To test the hypothesis that female prevalence is greater than expected among reported cases of torsades de pointes associated with cardiovascular drugs that prolong cardiac repolarization.
A MEDLINE search of the English-language literature for the period of 1980 through 1992, using the terms torsade de pointes, polymorphic ventricular tachycardia, atypical ventricular tachycardia, proarrhythmia, and drug-induced ventricular tachycardia, supplemented by pertinent references (dating back to 1964) from the reviewed articles and by personal communications with researchers involved in this field.
Ninety-three articles were identified describing at least one case of polymorphic ventricular tachycardia (with gender specified) associated with quinidine, procainamide hydrochloride, disopyramide, amiodarone, sotalol hydrochloride, bepridil hydrochloride, or prenylamine. A total of 332 patients were included in the analysis following application of prospectively defined criteria (eg, corrected QT [QTc] interval of 0.45 second or greater while receiving drug).
Clinical and electrocardiographic descriptors were extracted for analysis. Expected female prevalence for torsades de pointes associated with quinidine, procainamide, disopyramide, and aminodarone was conservatively estimated from gender-specific data reported for antiarrhythmic drug prescriptions in 1986, as derived from the National Disease and Therapeutic Index, a large pharmaceutical database; expected female prevalence for torsades de pointes associated with sotalol, bepridil, and prenylamine was assumed to be 50% or less since these agents are prescribed for male-predominant cardiovascular conditions.
Women made up 70% (95% confidence interval, 64% to 75%) of the 332 reported cases of cardiovascular-drug-related torsades de pointes, and a female prevalence exceeding 50% was observed in 20 (83%) of 24 studies having at least four included cases. When analyzed according to various descriptors, women still constituted the majority (range, 51% to 94% of torsades de pointes cases), irrespective of the presence or absence of underlying coronary artery or rheumatic heart disease, left ventricular dysfunction, type of underlying arrhythmia, hypokalemia, hypomagnesemia, bradycardia, concomitant digoxin treatment, or level of QTc at baseline or while receiving drug. When cases of torsades de pointes were analyzed by individual drug, observed female prevalence was always greater than expected, representing a statistically significant difference (P < .05) for all agents except procainamide.
These findings strongly suggest that women are more prone than men to develop torsades de pointes during administration of cardiovascular drugs that prolong cardiac repolarization. The pathophysiological basis for, and therapeutic implications of, this gender disparity should be further investigated.
验证以下假设：在与延长心脏复极的心血管药物相关的尖端扭转型室速报告病例中，女性患病率高于预期。
通过MEDLINE检索1980年至1992年期间的英文文献，使用术语“尖端扭转型室速”“多形性室性心动过速”“非典型室性心动过速”“致心律失常作用”和“药物性室性心动过速”，并辅以综述文章中相关参考文献（可追溯至1964年）以及与该领域研究人员的个人交流。
共识别出93篇文章，描述了至少1例与奎尼丁、盐酸普鲁卡因胺、丙吡胺、胺碘酮、盐酸索他洛尔、盐酸苄普地尔或普尼拉明相关的多形性室性心动过速（明确了性别）。在应用预先确定的标准（如接受药物治疗时校正QT[QTc]间期≥0.45秒）后，共有332例患者纳入分析。
提取临床和心电图描述符进行分析。根据1986年抗心律失常药物处方的性别特异性数据（源自大型制药数据库国家疾病和治疗指数），保守估计与奎尼丁、普鲁卡因胺、丙吡胺和胺碘酮相关的尖端扭转型室速的预期女性患病率；由于索他洛尔、苄普地尔和普尼拉明主要用于治疗以男性为主的心血管疾病，因此假设与它们相关的尖端扭转型室速的预期女性患病率为50%或更低。
在332例报告的与心血管药物相关的尖端扭转型室速病例中，女性占70%（95%置信区间为64%至75%），在至少纳入4例病例的24项研究中的20项（83%）中观察到女性患病率超过50%。根据各种描述符进行分析时，无论是否存在潜在冠状动脉或风湿性心脏病、左心室功能障碍、潜在心律失常类型、低钾血症、低镁血症、心动过缓、同时使用地高辛治疗，或基线或接受药物治疗时的QTc水平如何，女性仍占多数（占尖端扭转型室速病例的51%至94%）。按个体药物分析尖端扭转型室速病例时，观察到的女性患病率总是高于预期，除普鲁卡因胺外，所有药物的差异均具有统计学意义（P<0.05）。
这些发现强烈表明，在使用延长心脏复极的心血管药物期间，女性比男性更容易发生尖端扭转型室速。这种性别差异背后的病理生理基础及其治疗意义应进一步研究。
