Department of Cardiology and Internal Medicine, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK.
Royal Free Hospital, Royal Free London NHS Foundation Trust, Camden, UK.
Clin Toxicol (Phila). 2021 Mar;59(3):208-214. doi: 10.1080/15563650.2020.1788054. Epub 2020 Jul 1.
The neurocognitive benefits of donepezil are well recognised, but the potential side effects on cardiac conduction remain unclear.
To investigate whether long-term donepezil therapy is associated with electrocardiographic (ECG) changes and in particular to assess its effects on the QT interval.
We conducted a single centre retrospective analysis of patients admitted to our trust on donepezil therapy over a 12-month period. An admission resting 12-lead ECG was obtained and compared to their ECG prior to commencement of donepezil therapy to assess for any significant difference in ECG parameters.
We identified 59 patients suitable for analysis. PR (177.0 ± 29.0 ms vs. 186.1 ± 34.2 ms, = 0.04), QRS (101.7 ± 20.3 ms vs. 104.7 ± 22.3 ms, = 0.04) and QT (393.3 ± 35.6 ms vs. 411.9 ± 44.6 ms, = 0.002) interval prolongation were all associated with donepezil use. The increase in QT intervals remained significant on correction for heart rate; resulting in 8 (13.6%) patients developing high arrhythmogenic risk based on assessment using QT nomogram plots. Concomitant use of tricyclic antidepressants was associated with significant QT prolongation (QTcB: = 0.344, = 0.008, QTcFred: = 0.382, = 0.003, QTcFram: = 0.379, = 0.003, QTcH: = 0.352, = 0.006), while the use of rate-limiting calcium channel blockers was associated with significant PR prolongation ( = 0.314, = 0.030), and beta-blockers with a reduction in heart rate ( = 0.256, = 0.050).
Our results clearly demonstrate that long-term use of donepezil is associated with prolongation of the QT interval. We suggest ECG evaluation should take place before and after donepezil initiation, and clinicians should be even more vigilant in those prescribed tricyclic antidepressants.
多奈哌齐的神经认知益处已得到广泛认可，但它对心脏传导的潜在副作用仍不清楚。
研究长期多奈哌齐治疗是否与心电图（ECG）变化相关，特别是评估其对 QT 间期的影响。
我们对在我们信托中心接受多奈哌齐治疗的患者进行了为期 12 个月的单中心回顾性分析。获得入院静息 12 导联心电图，并与开始多奈哌齐治疗前的心电图进行比较，以评估心电图参数是否有任何显著差异。
我们确定了 59 名适合分析的患者。PR 间期（177.0±29.0ms 比 186.1±34.2ms， = 0.04）、QRS 间期（101.7±20.3ms 比 104.7±22.3ms， = 0.04）和 QT 间期（393.3±35.6ms 比 411.9±44.6ms， = 0.002）延长均与多奈哌齐的使用有关。在对心率进行校正后，QT 间期的延长仍然具有统计学意义；结果导致 8 名（13.6%）患者根据 QT 诺谟图评估出现高心律失常风险。三环类抗抑郁药的同时使用与显著的 QT 间期延长相关（QTcB： = 0.344， = 0.008，QTcFred： = 0.382， = 0.003，QTcFram： = 0.379， = 0.003，QTcH： = 0.352， = 0.006），而限速钙通道阻滞剂的使用与 PR 间期延长相关（ = 0.314， = 0.030），β受体阻滞剂与心率降低相关（ = 0.256， = 0.050）。
我们的结果清楚地表明，长期使用多奈哌齐与 QT 间期延长有关。我们建议在开始多奈哌齐治疗前后进行心电图评估，并且对于开处方三环类抗抑郁药的患者，临床医生应该更加警惕。
