Noordam Raymond, van den Berg Marten E, Niemeijer Maartje N, Aarts Nikkie, Leening Maarten J G, Deckers Jaap W, Hofman Albert, Rijnbeek Peter R, Eijgelsheim Mark, Kors Jan A, Stricker Bruno H, Visser Loes E
From the Departments of *Internal Medicine, †Epidemiology, ‡Medical Informatics, and §Cardiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam: ∥Inspectorate of Health Care; and ¶Apotheek Haagse Ziekenhuizen-HAGA, The Hague, The Netherlands.
J Clin Psychopharmacol. 2015 Jun;35(3):260-5. doi: 10.1097/JCP.0000000000000321.
A prolonged heart rate corrected QT interval (QTc) increases the risk of sudden cardiac death. Some methods of heart rate correction (notably Bazett) overestimate QTc in people with high heart rates. Studies suggest that tricyclic antidepressants (TCAs) can prolong the QTc and increase heart rate. Therefore, we aimed to study whether TCA-induced QTc prolongation is a false-positive observation due to overestimation at high heart rates. For this, we included 12,734 participants from the prospective population-based Rotterdam Study, with a total of 27,068 electrocardiograms (ECGs), of which, 331 during TCA use. Associations between use of TCAs, QTc, and heart rate were studied with linear repeated measurement analyses. QT was corrected for heart rate according to Bazett (QTcBazett), Fridericia (QTcFridericia), or a correction based on regression coefficients obtained from the Rotterdam Study data (QTcStatistical). On ECGs recorded during TCA use, QTcBazett was 6.5 milliseconds (95% confidence interval, 4.0-9.0) longer, and heart rate was 5.8 beats per minute (95% confidence interval, 4.7-6.9) faster than during nonuse. QTcFridericia and QTcStatistical were not statistically significantly longer during TCA use than during nonuse. Furthermore, QTcBazett was similar for ECGs recorded during TCA use and nonuse after statistical adjustment for heart rate. According to our results, TCA use does not seem to be associated with QTc prolongation. Therefore, the current advice of regulatory authorities to restrict the use of these drugs and to do regular checkups of the QTc may need to be revised. Other formulas, like Fridericia's, might be preferred.
心率校正后的QT间期(QTc)延长会增加心源性猝死的风险。一些心率校正方法(尤其是Bazett法)会高估心率较快者的QTc。研究表明,三环类抗抑郁药(TCA)可延长QTc并加快心率。因此,我们旨在研究TCA引起的QTc延长是否是由于高心率时的高估而导致的假阳性观察结果。为此,我们纳入了基于鹿特丹前瞻性人群研究的12734名参与者,共有27068份心电图(ECG),其中331份是在使用TCA期间记录的。通过线性重复测量分析研究了TCA使用、QTc和心率之间的关联。根据Bazett法(QTcBazett)、Fridericia法(QTcFridericia)或基于从鹿特丹研究数据获得的回归系数进行校正(QTcStatistical)来校正心率。在使用TCA期间记录的心电图上,QTcBazett比未使用时延长了6.5毫秒(95%置信区间,4.0 - 9.0),心率比未使用时每分钟快5.8次(95%置信区间,4.7 - 6.9)。使用TCA期间的QTcFridericia和QTcStatistical与未使用时相比,在统计学上没有显著延长。此外,在对心率进行统计调整后,使用TCA期间和未使用时记录的心电图的QTcBazett相似。根据我们的结果,使用TCA似乎与QTc延长无关。因此,监管机构目前关于限制这些药物使用并定期检查QTc的建议可能需要修订。其他公式,如Fridericia公式,可能更可取。