Division of Cardiology, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.
J Cardiovasc Electrophysiol. 2012 May;23(5):527-33. doi: 10.1111/j.1540-8167.2011.02231.x. Epub 2011 Dec 2.
Methadone is associated with QTc prolongation and sudden death in susceptible patients. We sought to investigate whether there is a gender-based difference in susceptibility to methadone-associated QTc prolongation in heroin-dependent patients receiving a low-dose treatment regimen.
A cross-sectional assessment of dose and gender effects was performed in 283 patients (229 males, 54 females) who received a 12-lead ECG for QTc measurement 59 days (interquartile range: 36-288 days) after methadone treatment. To determine the effects of methadone over time, a subset of 150 participants (126 men, 24 women) who underwent a 12-lead ECG before and 37 days (interquartile range: 32-44 days) after methadone treatment were selected.
In the cross-sectional study, a significant dose-dependent interaction between methadone and QTc (r = 0.201, P = 0.0007) was observed in individuals receiving a median methadone dose of 40 mg/day (interquartile range: 30-60 mg/day). The methadone-QTc correlation was significant in males (r = 0.210, P = 0.0014) but not in females (r = 0.164, P = 0.2363). The longitudinal assessment of methadone's effects over a 6-month period showed that 60.7% of individuals experienced an increase in QTc compared to baseline data. The adjusted QTc significantly increased from 418.5 to 426.9 milliseconds in males (P < 0.0001), compared to an insignificant change in females (437.7 milliseconds vs 441.1 milliseconds, P = 0.468).
Low-dose methadone therapy shows dose-dependent QTc prolongation and is associated with significant QTc lengthening within 6 months of treatment initiation. Men are more susceptible than women to low-dose methadone-associated QTc prolongation.
在易患患者中，美沙酮与 QTc 延长和猝死有关。我们试图研究在接受低剂量治疗方案的海洛因依赖患者中，美沙酮相关 QTc 延长的易感性是否存在性别差异。
对 283 名患者（229 名男性，54 名女性）进行了剂量和性别影响的横断面评估，这些患者在接受美沙酮治疗后 59 天（四分位距：36-288 天）进行了 12 导联心电图以测量 QTc。为了确定美沙酮随时间的影响，选择了 150 名参与者（126 名男性，24 名女性）的亚组，他们在接受美沙酮治疗前和 37 天（四分位距：32-44 天）进行了 12 导联心电图。
在横断面研究中，在接受中位数美沙酮剂量为 40 毫克/天（四分位距：30-60 毫克/天）的个体中，观察到美沙酮和 QTc 之间存在显著的剂量依赖性相互作用（r = 0.201，P = 0.0007）。美沙酮-QTc 相关性在男性中具有统计学意义（r = 0.210，P = 0.0014），但在女性中无统计学意义（r = 0.164，P = 0.2363）。在 6 个月的时间内对美沙酮作用的纵向评估显示，与基线数据相比，60.7%的个体 QTc 增加。与女性相比，男性的校正 QTc 从 418.5 毫秒显著增加到 426.9 毫秒（P < 0.0001），而女性无明显变化（437.7 毫秒与 441.1 毫秒，P = 0.468）。
低剂量美沙酮治疗显示剂量依赖性 QTc 延长，并与治疗开始后 6 个月内 QTc 显著延长相关。男性比女性更容易受到低剂量美沙酮相关 QTc 延长的影响。
