From the Department of Neurology (M.R.C.), Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (S.T.S.), Division of Health Care Delivery Research (L.R.S., P.A.N.), Division of Epilepsy, Department of Neurology (E.L.S.), and Department of Cardiovascular Diseases (M.J.A., P.A.N.), Mayo Clinic, Rochester, MN.
Neurology. 2024 May 14;102(9):e209177. doi: 10.1212/WNL.0000000000209177. Epub 2024 Apr 1.
Levetiracetam is a widely used antiseizure medication. Recent concerns have been raised regarding the potential prolongation of the QT interval by levetiracetam and increased risk of sudden cardiac death. This could have profound implications for patient safety and for prescribing practice. This study assessed the potential association of levetiracetam with cardiac outcomes related to QT interval prolongation. We compared outcomes of patients taking levetiracetam with those taking oxcarbazepine as a comparator medication that has not been associated with prolongation of the QT interval.
The sample included patients who were newly prescribed levetiracetam or oxcarbazepine from January 31, 2010, to December 31, 2019, using administrative claims data from the OptumLabs Data Warehouse (OLDW). The analysis focused on a combined endpoint of sudden cardiac death or ventricular arrythmia, which are both linked to QT interval prolongation. We used a new user design and selected oxcarbazepine as an active comparator with levetiracetam to minimize bias. We used propensity score weighting to balance the levetiracetam and oxcarbazepine cohorts and then performed weighted Cox regressions to evaluate the association of levetiracetam with the combined endpoint.
We identified 104,655 enrollees taking levetiracetam and 39,596 enrollees taking oxcarbazepine. At baseline, enrollees taking levetiracetam were older, more likely to have diagnosed epilepsy, and more likely to have diagnosed comorbidities including hypertension, cerebrovascular disease, and coronary artery disease. In the main analysis, we found no significant difference between levetiracetam and oxcarbazepine in the rate of the combined endpoint for the Cox proportional hazards model (hazard ratio [HR] 0.79, 95% CI 0.42-1.47) or Cox regression with time-varying characteristics (HR 0.78, 95% CI 0.41-1.50).
When compared with oxcarbazepine, levetiracetam does not correlate with increased risk of ventricular arrythmia and sudden cardiac death. Our finding does not support the concern for cardiac risk to indicate restriction of levetiracetam use nor the requirement of cardiac monitoring when using it.
This study provides Class II evidence that sudden cardiac death and ventricular arrythmia are not more frequent in patients older than 17 years newly prescribed levetiracetam, compared with those prescribed oxcarbazepine.
左乙拉西坦是一种广泛使用的抗癫痫药物。最近有人担心左乙拉西坦可能会延长 QT 间期，并增加心脏性猝死的风险。这可能对患者安全和处方实践产生深远影响。本研究评估了左乙拉西坦与 QT 间期延长相关的心脏结局的潜在关联。我们比较了服用左乙拉西坦的患者和服用奥卡西平的患者的结局，奥卡西平是一种与 QT 间期延长无关的对照药物。
本研究使用来自 OptumLabs Data Warehouse (OLDW) 的行政索赔数据，对 2010 年 1 月 31 日至 2019 年 12 月 31 日期间新处方左乙拉西坦或奥卡西平的患者进行了抽样。分析集中在与 QT 间期延长相关的心脏性猝死或室性心律失常的联合终点上。我们使用新用户设计，并选择奥卡西平作为与左乙拉西坦的活性对照，以尽量减少偏倚。我们使用倾向评分加权来平衡左乙拉西坦和奥卡西平队列，然后进行加权 Cox 回归分析，以评估左乙拉西坦与联合终点的关联。
我们确定了 104655 名服用左乙拉西坦的患者和 39596 名服用奥卡西平的患者。在基线时，服用左乙拉西坦的患者年龄较大，更有可能被诊断为癫痫，并且更有可能患有高血压、脑血管疾病和冠状动脉疾病等合并症。在主要分析中，我们在 Cox 比例风险模型（风险比 [HR] 0.79，95%CI 0.42-1.47）或具有时变特征的 Cox 回归中，未发现左乙拉西坦和奥卡西平之间联合终点的发生率有显著差异（HR 0.78，95%CI 0.41-1.50）。
与奥卡西平相比，左乙拉西坦与室性心律失常和心脏性猝死的风险增加无关。我们的发现不支持对心脏风险的担忧，表明不应限制左乙拉西坦的使用，也不需要在使用时进行心脏监测。
本研究提供了 II 级证据，表明与新处方奥卡西平的患者相比，年龄大于 17 岁的新处方左乙拉西坦的患者中，心脏性猝死和室性心律失常并不更常见。
