Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China.; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.; Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands.
Am Heart J. 2022 Jan;243:177-186. doi: 10.1016/j.ahj.2021.09.014. Epub 2021 Oct 2.
Stopping renin-angiotensin system inhibitors (RASi) after an episode of hyperkalemia is common but may involve therapeutic compromises, in that the cessation of RASi deprives patients of their beneficial cardiovascular effects.
Observational study from the Stockholm Creatinine Measurements (SCREAM) project including patients initiating RASi in routine care and surviving a first-detected episode of hyperkalemia (potassium >5.0 mmol/L). We used target trial emulation techniques based on cloning, censoring and weighting to compare stopping vs. continuing RASi within 6 months after hyperkalemia. Outcomes were 3-year risks of mortality, major adverse cardiovascular events (MACE, composite of cardiovascular death, myocardial infarction and stroke hospitalization) and recurrent hyperkalemia. Of 5669 new users of RASi who developed hyperkalemia (median age 72 years, 44% women), 1425 (25%) stopped RASi therapy within 6 months. Compared with continuing RASi, stopping therapy was associated with a higher 3-year risk of death (absolute risk difference 10.8%; HR 1.49, 95% CI 1.34-1.64) and MACE (risk difference 4.7%; HR 1.29, 1.14-1.45), but a lower risk of recurrent hyperkalemia (risk difference -9.5%; HR 0.76, 0.69-0.84). Results were consistent for events following potassium of >5.0 or >5.5 mmol/L, after censoring when the treatment decision was changed, across prespecified subgroups, and after adjusting for albuminuria.
These findings suggest that stopping RASi after hyperkalemia may be associated with a lower risk of recurrence of hyperkalemia, but higher risk of death and cardiovascular events.
在发生高钾血症后，停止肾素-血管紧张素系统抑制剂（RASi）的使用较为常见，但可能会带来治疗上的妥协，因为停止 RASi 会使患者失去其有益的心血管作用。
本研究为来自斯德哥尔摩肌酐测量（SCREAM）项目的观察性研究，纳入了在常规治疗中开始使用 RASi 并首次发生高钾血症（血钾>5.0mmol/L）的患者。我们使用基于克隆、删失和加权的目标试验模拟技术，比较了高钾血症后 6 个月内停止和继续使用 RASi 的情况。主要结局为 3 年死亡率、主要不良心血管事件（MACE，心血管死亡、心肌梗死和卒中住院的复合结局）和复发性高钾血症的风险。在 5669 例新使用 RASi 并发生高钾血症的患者中（中位年龄 72 岁，44%为女性），有 1425 例（25%）在 6 个月内停止了 RASi 治疗。与继续使用 RASi 相比，停止治疗与 3 年死亡率（绝对风险差异 10.8%；HR 1.49，95%CI 1.34-1.64）和 MACE（风险差异 4.7%；HR 1.29，1.14-1.45）风险增加有关，但与复发性高钾血症（风险差异-9.5%；HR 0.76，0.69-0.84）风险降低有关。当改变治疗决策时进行删失、在预设亚组内以及在调整白蛋白尿后，结果在血钾>5.0mmol/L 或>5.5mmol/L 后、在所有事件中均一致。
这些发现表明，在高钾血症后停止 RASi 可能与低钾血症的复发风险降低有关，但与死亡和心血管事件的风险增加有关。
