University of North Carolina Kidney Center , Division of Nephrology and Hypertension, Department of Medicine, UNC School of Medicine, Chapel Hill, NC, USA.
Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Nephrol Dial Transplant. 2022 Oct 19;37(11):2241-2252. doi: 10.1093/ndt/gfac214.
Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs).
We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus <4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study.
The study included 25 099 patients: 11 107 (44.3%) higher QT-prolonging potential SSRI new users and 13 992 (55.7%) lower QT-prolonging potential SSRI new users. Overall, higher versus lower QT-prolonging potential SSRI use was not associated with SCD [weighted HR 1.03 (95% CI 0.86-1.24)]. However, a greater risk of SCD was associated with higher versus lower QT-prolonging potential SSRI use among patients with baseline potassium gradients ≥4 mEq/l but not among those with gradients <4 mEq/l [weighted HR 2.17 (95% CI 1.16-4.03) versus 0.95 (0.78-1.16)]. Nested case-control analyses yielded analogous results.
The serum-to-dialysate potassium gradient may modify the association between higher versus lower QT-prolonging SSRI use and SCD among people receiving HD. Minimizing the potassium gradient in the setting of QT-prolonging medication use may be warranted.
低钾血症是药物引起 QT 延长的一个危险因素。血液透析（HD）过程中血清与透析液之间的钾梯度增大，可能会增加选择性 5-羟色胺再摄取抑制剂（SSRIs）的致心律失常风险。
我们进行了一项队列研究，使用了美国肾脏数据系统（US Renal Data System）和一家大型透析供应商 2007-2017 年的数据，以检验血清与透析液之间的钾梯度是否会改变 SSRIs 的心脏安全性。我们采用新用户设计，比较了新接受高（西酞普兰、艾司西酞普兰）与低（氟西汀、氟伏沙明、帕罗西汀、舍曲林）QT 延长潜能 SSRIs 治疗的 HD 患者在 1 年内发生心源性猝死（SCD）的风险，总体和按基线钾梯度（≥4 与 <4 mEq/l）分层。我们使用逆概率治疗加权生存模型来估计加权风险比（HRs）和 95%置信区间（CIs），并进行了一项确认性的巢式病例对照研究。
研究纳入了 25099 名患者：11107 名（44.3%）为高 QT 延长潜能 SSRIs 新使用者，13992 名（55.7%）为低 QT 延长潜能 SSRIs 新使用者。总体而言，与低 QT 延长潜能 SSRIs 相比，高 QT 延长潜能 SSRIs 的使用与 SCD 无关[加权 HR 1.03（95%CI 0.86-1.24）]。然而，在基线钾梯度≥4 mEq/l 的患者中，与低 QT 延长潜能 SSRIs 相比，高 QT 延长潜能 SSRIs 的使用与 SCD 风险增加相关，但在基线钾梯度 <4 mEq/l 的患者中则没有这种相关性[加权 HR 2.17（95%CI 1.16-4.03）与 0.95（0.78-1.16）]。巢式病例对照分析得出了类似的结果。
血清与透析液之间的钾梯度可能会改变与接受 HD 的人群中高与低 QT 延长 SSRIs 使用相关的 SCD 风险之间的关联。在使用 QT 延长药物时，应尽量减小钾梯度。
