Cardiovascular Diseases Unit, Cardio Thoracic and Vascular Department, Le Scotte Hospital University of Siena, Viale Bracci, Siena 53100, Italy.
Cardiovascular Diseases Unit, Cardio Thoracic and Vascular Department, Le Scotte Hospital University of Siena, Siena, Italy.
Ther Adv Cardiovasc Dis. 2024 Jan-Dec;18:17539447241285136. doi: 10.1177/17539447241285136.
Sacubitril/valsartan (S/V) is a cornerstone treatment for heart failure (HF). Beneficial effects on hospitalization rates, mortality, and left ventricular remodeling have been observed in patients with heart failure and reduced ejection fraction (HFrEF). Despite the positive results, the influence of S/V on renal function during long-term follow-up has received little attention.
We investigated the long-term effects of S/V therapy on renal function in a large cohort of patients with HFrEF. Additionally, we examined the effects of the drug in patients with chronic kidney disease (CKD) compared to those with preserved renal function and identified primary risk characteristics.
We studied 776 outpatients with HFrEF and left ventricular ejection fraction (LVEF) <40% from an observational registry of the Italian Society of Cardiology, all receiving optimized standard-of-care therapy with S/V. The patients were included in a multicentric open-label registry from 11 Italian academic hospitals. Kidney function was evaluated at baseline, after 6 months of S/V, and at 4 years. Patients were followed-up through periodic clinical visits.
During a 48-month follow-up period, 591 patients remained stable and 185 patients (24%) experienced adverse events (85 deaths and 126 hospitalizations). S/V therapy marginally affects renal function during the follow-up period (estimated glomerular filtration rate (eGFR) at baseline 72.01 vs eGFR at follow-up 70.38 ml/min/m, = 0.01; and creatinine was 1.06 at baseline vs 1.10 at follow-up, < 0.04). Among patients who maintained preserved renal function, 35% were in Dose 3 and 10% dropped out of S/V therapy ( < 0.006). Univariate analysis showed that Drop-out of S/V (HR 2.73 [2.01, 3.71], < 0.001), history of previous HF hospitalization (HR 1.75 [1.30, 2.36], < 0.001), advanced NYHA class (HR 2.14 [1.60, 2.86], < 0.001), NT-proBNP values >1000 pg/ml (HR 1.95[1.38, 2.77], < 0.001), furosemide dose >50 mg (HR 2.04 [1.48, 2.82], < 0.001), and creatinine values >1.5 mg/dl occurred during follow-up (HR 1.74 [1.24, 2.43], < 0.001) were linked to increased risk. At multivariable analysis, increased doses of loop diuretics, advanced NYHA class, creatinine >1.5 mg/dl, and atrial fibrillation were independent predictors of adverse events.
Long-term S/V therapy is associated with improved outcomes and renal protection in patients with HFrEF. This effect is more pronounced in patients who tolerate escalating doses. The positive effects of the drug are maintained in both CKD and preserved renal function. Future research may study the safety and underlying causes of current protection.
沙库巴曲缬沙坦（S/V）是心力衰竭（HF）的基石治疗方法。在射血分数降低的心力衰竭（HFrEF）患者中，观察到 S/V 治疗可降低住院率、死亡率和左心室重构。尽管有积极的结果，但 S/V 在长期随访期间对肾功能的影响却很少受到关注。
我们研究了 S/V 治疗对 HFrEF 患者肾功能的长期影响。此外，我们还比较了 S/V 在慢性肾脏病（CKD）患者和肾功能正常患者中的作用，并确定了主要的风险特征。
我们研究了意大利心脏病学会观察性登记处的 776 名 HFrEF 门诊患者，所有患者的左心室射血分数（LVEF）<40%，均接受 S/V 优化的标准治疗。患者来自意大利 11 家学术医院的多中心开放标签登记处。在基线、S/V 治疗 6 个月和 4 年后评估肾功能。通过定期临床访视对患者进行随访。
在 48 个月的随访期间，591 名患者病情稳定，185 名患者（24%）发生不良事件（85 例死亡，126 例住院）。S/V 治疗在随访期间对肾功能有轻微影响（基线时估计肾小球滤过率[eGFR]为 72.01 ml/min/m，随访时为 70.38 ml/min/m， = 0.01；肌酐基线时为 1.06，随访时为 1.10， < 0.04）。在肾功能正常的患者中，35%的患者使用了 3 剂量，10%的患者停止使用 S/V 治疗（ < 0.006）。单因素分析显示，S/V 停药（HR 2.73 [2.01, 3.71]， < 0.001）、既往心力衰竭住院史（HR 1.75 [1.30, 2.36]， < 0.001）、晚期 NYHA 分级（HR 2.14 [1.60, 2.86]， < 0.001）、NT-proBNP 值>1000 pg/ml（HR 1.95[1.38, 2.77]， < 0.001）、呋塞米剂量>50 mg（HR 2.04 [1.48, 2.82]， < 0.001）和随访期间肌酐值>1.5 mg/dl（HR 1.74 [1.24, 2.43]， < 0.001）与风险增加有关。多因素分析显示，递增剂量的袢利尿剂、晚期 NYHA 分级、肌酐值>1.5 mg/dl 和心房颤动是不良事件的独立预测因素。
长期 S/V 治疗可改善射血分数降低的心力衰竭患者的预后和肾功能保护。在能耐受递增剂量的患者中，这种作用更为明显。该药的积极作用在 CKD 和肾功能正常的患者中均能维持。未来的研究可能会研究目前保护作用的安全性和潜在原因。
