Nordberg Backelin Charlotte, Fu Michael, Ljungman Charlotta
Department of Molecular and Clinical Medicine/Cardiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
ESC Heart Fail. 2020 Jun;7(3):1049-1055. doi: 10.1002/ehf2.12644. Epub 2020 Feb 6.
Sacubitril/Valsartan (Sac/Val) was proven more effective than enalapril for symptomatic patients with heart failure (HF) with reduced ejection fraction (HFrEF). This study aimed to investigate eligibility, titration, and tolerability for Sac/Val in a real-world clinical setting.
This retrospective cohort study consists of two parts. In Part 1 (eligibility study), all patients discharged from Sahlgrenska University Hospital due to HF were consecutively included during 1 year. Data from the patients' medical records were collected. Patients were adjudicated to be eligible based on European Society of Cardiology (ESC) criteria for angiotensin receptor neprilysin inhibitor (ARNI) with the exception of N-terminal (NT)-proBNP levels. Patients who received <50% of target dose angiotensin-converting enzyme/angiotensin receptor blocker and otherwise fulfilled ESC criteria were adjudicated to be potentially eligible. In Part 2 (tolerability study), all patients receiving Sac/Val during the same period were included. Medical data regarding dose, titration, and adverse effects and events were registered. A total of 1355 patients (mean age 78 ± 13 years) were hospitalized for HF and 619 patients had an EF ≤40%. Twenty percent were eligible for initiation of ARNI, and additionally 8% were potentially eligible. In all 95 patients (mean age 65 ± 12 years) were initiated with Sac/Val, which correlates to 13%. The patients who were initiated were younger (65 years), more often had dilated cardiomyopathy (31%), more often were on guideline-directed medical therapy, and had a higher frequency of cardiac resynchronization therapy and implantable cardioverter-defibrillator compared with the patients who did not receive Sac/Val. Of the initiated patients, 59% reached target dose of Sac/Val, and 15% discontinued due to adverse effects. The most common cause of discontinuation was benign gastrointestinal adverse effects, followed by elevated creatinine, malaise, and vertigo. Female gender [odds ratio (OR) 3.58; 95% CI 1.07-2.00; P = 0.038] and NT-proBNP ≥ median level (OR 0.48; 95% CI 0.26-0.90; P = 0.021) was associated with termination of the medication.
Among HFrEF patients in this real-world cohort, 20% were eligible for ARNI; however, only 13% received the treatment. Sac/Val was well tolerated, but 41% of the patients did not reach target dose. How this affects outcome is not known and needs further investigation.
对于射血分数降低的心力衰竭（HFrEF）症状性患者，已证实沙库巴曲缬沙坦（Sac/Val）比依那普利更有效。本研究旨在调查Sac/Val在真实临床环境中的适用性、滴定情况和耐受性。
这项回顾性队列研究由两部分组成。在第1部分（适用性研究）中，连续纳入了1年内因心力衰竭从萨尔格伦斯卡大学医院出院的所有患者。收集患者病历中的数据。除N末端（NT）-proBNP水平外，根据欧洲心脏病学会（ESC）的血管紧张素受体脑啡肽酶抑制剂（ARNI）标准判定患者是否符合条件。接受目标剂量血管紧张素转换酶/血管紧张素受体阻滞剂不足50%但其他方面符合ESC标准的患者被判定为可能符合条件。在第2部分（耐受性研究）中，纳入了同期接受Sac/Val治疗的所有患者。记录有关剂量、滴定以及不良反应和事件的医疗数据。共有1355例患者（平均年龄78±13岁）因心力衰竭住院，619例患者射血分数（EF）≤40%。20%的患者符合启动ARNI的条件，另外8%可能符合条件。共有95例患者（平均年龄65±12岁）开始使用Sac/Val，占13%。与未接受Sac/Val的患者相比，开始使用该药物的患者更年轻（65岁），扩张型心肌病的发生率更高（31%），更常接受指南指导的药物治疗，心脏再同步治疗和植入式心律转复除颤器的使用频率更高。在开始使用药物的患者中，59%达到了Sac/Val的目标剂量，15%因不良反应停药。最常见的停药原因是良性胃肠道不良反应，其次是肌酐升高、不适和眩晕。女性[比值比（OR）3.58；95%置信区间（CI）1.07 - 2.00；P = 0.038]和NT-proBNP≥中位数水平（OR 0.48；95% CI 0.26 - 0.90；P = 0.021）与停药有关。
在这个真实世界队列中的HFrEF患者中，20%符合ARNI治疗条件；然而，只有13%接受了该治疗。Sac/Val耐受性良好，但41%的患者未达到目标剂量。这对预后有何影响尚不清楚，需要进一步研究。
