Hyperkalemia after starting renin-angiotensin system inhibitors has been shown to be subsequently associated with a higher risk of cardiovascular and kidney outcomes. However, whether to continue or discontinue the drug after hyperkalemia remains unclear.

Data came from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, which included a run-in period where all participants initiated angiotensin-converting enzyme inhibitor–based therapy (a fixed combination of perindopril and indapamide). The study population was taken as patients with type 2 diabetes with normokalemia (serum potassium of 3.5 to <5.0 mEq/L) at the start of run-in. Potassium was remeasured 3 weeks later when a total of 9694 participants were classified into hyperkalemia (≥5.0 mEq/L), normokalemia, and hypokalemia (<3.5 mEq/L) groups. After run-in, patients were randomized to continuation of the angiotensin-converting enzyme inhibitor–based therapy or placebo; major macrovascular, microvascular, and mortality outcomes were analyzed using Cox regression during the following 4.4 years (median).

During active run-in, 556 (6%) participants experienced hyperkalemia. During follow-up, 1505 participants experienced the primary composite outcome of major macrovascular and microvascular events. Randomized treatment of angiotensin-converting enzyme inhibitor–based therapy significantly decreased the risk of the primary outcome (38.1 versus 42.0 per 1000 person-years; hazard ratio, 0.91; 95% confidence interval, 0.83 to 1.00; P=0.04) compared with placebo. The magnitude of effects did not differ across subgroups defined by short-term changes in serum potassium during run-in (P for heterogeneity =0.66). Similar consistent treatment effects were also observed for all-cause death, cardiovascular death, major coronary events, major cerebrovascular events, and new or worsening nephropathy (P for heterogeneity ≥0.27).

Continuation of angiotensin-converting enzyme inhibitor–based therapy consistently decreased the subsequent risk of clinical outcomes, including cardiovascular and kidney outcomes and death, regardless of short-term changes in serum potassium.

Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), NCT00145925

开始使用肾素-血管紧张素系统抑制剂后的高钾血症已被证明与心血管和肾脏结局的较高风险相关。然而，高钾血症后是否继续用药或停药尚不清楚。

数据来自糖尿病和血管疾病行动：Preterax 和 Diamicron 改良释放控制评估 (ADVANCE) 试验，其中包括一个磨合期，所有参与者均开始基于血管紧张素转换酶抑制剂的治疗（培哚普利和吲达帕胺的固定组合） ）。研究人群为磨合开始时血钾正常（血清钾为 3.5 至 <5.0 mEq/L）的 2 型糖尿病患者。3周后重新测量钾含量，共有9694名参与者被分为高钾血症（≥5.0 mEq/L）、正常钾血症和低钾血症（<3.5 mEq/L）组。磨合后，患者被随机分配继续接受基于血管紧张素转换酶抑制剂的治疗或安慰剂；使用 Cox 回归分析接下来 4.4 年（中位数）的主要大血管、微血管和死亡率结果。

在主动磨合期间，556 名 (6%) 参与者出现了高钾血症。在随访期间，1505 名参与者经历了主要大血管和微血管事件的主要复合结果。与安慰剂相比，基于血管紧张素转换酶抑制剂的随机治疗显着降低了主要结局的风险（每 1000 人年 38.1 对比 42.0；风险比，0.91；95% 置信区间，0.83 至 1.00；P = 0.04 ）。由磨合期间血清钾的短期变化定义的亚组之间的影响程度没有差异（异质性P =0.66）。对于全因死亡、心血管死亡、主要冠脉事件、主要脑血管事件以及新发肾病或肾病恶化，也观察到类似的一致治疗效果（异质性P ≥0.27）。

无论血清钾的短期变化如何，继续以血管紧张素转换酶抑制剂为基础的治疗持续降低随后的临床结果风险，包括心血管和肾脏结果以及死亡。

在糖尿病和血管疾病中的作用：Preterax 和 Diamicron 改良释放控制评估 (ADVANCE)，NCT00145925