Ferreira João Pedro, Konstam Marvin, Rossignol Patrick, Kiernan Michael S, Zannad Faiez
UnIC@RISE, Cardiovascular R&D Center, Faculty of Medicine, University of Porto, Porto, Portugal;; Université de Lorraine, Centre d'Investigation Clinique-Plurithématique INSERM CIC-P 1433, and INSERM U1116 CHRU Nancy, F-CRIN INI-CRCT, Nancy France; and.
The CardioVascular Center, Tufts Medical Center, Boston, Massachusetts.
J Card Fail. 2023 Jan;29(1):45-52. doi: 10.1016/j.cardfail.2022.09.008. Epub 2022 Oct 14.
Patients with heart failure (HF) experience frequent alterations of serum potassium. Despite the high risk of events associated with hypokalemia, hyperkalemia is feared by clinicians and often leads to interruption or discontinuation of renin-angiotensin-aldosterone system inhibitors. Data on serum potassium of patients treated with different doses of renin-angiotensin-aldosterone system inhibitors are scarce.
The effects of high-dose vs low-dose losartan on clinical outcomes in patients with heart failure (HEAAL) trial randomized 3834 patients with HFrEF intolerant to angiotensin-converting enzyme inhibitors to losartan 150 mg/d (high dose) vs 50 mg/d (low dose). We studied the associations of serum potassium (baseline and time updated) with study outcomes and the effect of the randomized treatment on serum potassium. Patients with higher baseline potassium were older, had diabetes, poorer renal function, and used mineralocorticoid receptor antagonists more frequently. In time-updated models, hyperkalemia (>5.0 or ≥5.5 mmol/L) was not associated with cardiovascular death or the composite of cardiovascular death or HF hospitalization. Hypokalemia (serum potassium of ≤3.5 mmol/L, in particular) was associated with a higher risk of the composite of cardiovascular death or HF hospitalization (hazard ratio [HR] 1.58, 95% confidence interval [CI] 1.19-2.08), all-cause death (HR 1.68, 95% CI 1.26-2.24), and sudden cardiac death or resuscitated cardiac arrest (HR 1.74, 95% CI 1.11-2.73). High-dose losartan decreased the risk of hypokalemia (HR 0.77, 95% CI 0.63-0.92) and increased the risk of hyperkalemia (HR 1.21, 95% CI 1.05-1.39). High-dose losartan decreased the composite of cardiovascular death or HF hospitalizations consistently across the full spectrum of serum potassium at baseline (interaction P = .85).
In patients with HF with reduced ejection fraction intolerant to angiotensin-converting enzyme inhibitors and treated with either high- or low-dose losartan, incident hypokalemia had a stronger association with poor outcomes than incident hyperkalemia. High-dose losartan reduced the incidence of hypokalemia, and its benefits were maintained across the full spectrum of serum potassium.
心力衰竭（HF）患者血清钾常发生变化。尽管低钾血症相关事件风险很高，但临床医生担心高钾血症，且这常导致肾素 - 血管紧张素 - 醛固酮系统抑制剂中断或停用。关于不同剂量肾素 - 血管紧张素 - 醛固酮系统抑制剂治疗患者血清钾的数据很少。
高剂量与低剂量氯沙坦对心力衰竭患者临床结局的影响（HEAAL）试验将3834例对血管紧张素转换酶抑制剂不耐受的射血分数降低的心力衰竭（HFrEF）患者随机分为氯沙坦150 mg/d（高剂量）组和50 mg/d（低剂量）组。我们研究了血清钾（基线和随时间更新）与研究结局的关联以及随机治疗对血清钾的影响。基线血钾较高的患者年龄更大、患有糖尿病、肾功能较差且更频繁使用盐皮质激素受体拮抗剂。在随时间更新的模型中，高钾血症（>5.0或≥5.5 mmol/L）与心血管死亡或心血管死亡或HF住院的复合结局无关。低钾血症（尤其是血清钾≤3.5 mmol/L）与心血管死亡或HF住院的复合结局（风险比[HR] 1.58，95%置信区间[CI] 1.19 - 2.08）、全因死亡（HR 1.68，95% CI 1.26 - 2.24）以及心源性猝死或心脏复苏后骤停（HR 1.74，95% CI 1.11 - 2.73）风险较高相关。高剂量氯沙坦降低了低钾血症风险（HR 0.77，95% CI 0.63 - 0.92）并增加了高钾血症风险（HR 1.21，95% CI 1.05 - 1.39）。在基线血清钾的整个范围内，高剂量氯沙坦一致降低了心血管死亡或HF住院的复合结局（交互P = 0.85）。
在对血管紧张素转换酶抑制剂不耐受且接受高剂量或低剂量氯沙坦治疗的射血分数降低的心力衰竭患者中，新发低钾血症比新发高钾血症与不良结局的关联更强。高剂量氯沙坦降低了低钾血症的发生率，且其益处贯穿血清钾的整个范围得以维持。
