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AIMS

Ivabradine and sacubitril/valsartan are second-line therapies for patients with heart failure and reduced ejection fraction (HFrEF) based on guideline recommendations. We aimed to evaluate the synergistic effects of these two medications.

METHODS AND RESULTS

Patients' data were extracted from a multicentre database between 2016 and 2018. Patients were classified into (1) Simultaneous group: simultaneous prescription of ivabradine and sacubitril/valsartan within 6 weeks; (2A) Sequential group, ivabradine-first: ivabradine was prescribed first, followed by sacubitril/valsartan; and (2B) Sequential group, sacubitril/valsartan-first: sacubitril/valsartan was prescribed first, followed by ivabradine. A total of 464 patients with HFrEF were enrolled. Cardiovascular death and/or unplanned re-hospitalizations for HF were less frequent (28.6% vs. 44.8%, P = 0.01), and the improvement of left ventricular ejection fraction (LVEF) was significantly greater in patients from the Simultaneous group than those from the Sequential group (∆LVEF 12.8 ± 12.9% vs. 9.3 ± 12.6%, P = 0.007). Among Sequential subgroups, the ivabradine-first treatment decreased heart rate and increased systolic blood pressure (SBP) compared with sacubitril/valsartan-first treatment (∆heart rate -9.1 ± 12.9 b.p.m. vs. 2.6 ± 16.0 b.p.m., P < 0.001; ∆SBP 4.6 ± 16.5 mmHg vs. -4.8 ± 17.2 mmHg, P < 0.001), whereas sacubitril/valsartan-first treatment showed a higher degree of LVEF improvement (∆LVEF 3.6 ± 7.8% vs. 0.7 ± 7.7%, P = 0.002) than ivabradine-first treatment. At the end of follow-up, SBP, LVEF, and left ventricular volume were comparable between two Sequential subgroups.

CONCLUSIONS

Among patients with HFrEF, simultaneous rather than sequential treatment with sacubitril/valsartan and ivabradine was a better strategy to reduce adverse events and achieve left ventricular reverse remodelling. Ivabradine treatment had a more significant benefit on improving haemodynamic stability, whereas sacubitril/valsartan treatment showed a more significant effect on improving LVEF.

目的

根据指南建议，伊伐布雷定和沙库巴曲缬沙坦是射血分数降低的心力衰竭（HFrEF）患者的二线治疗药物。我们旨在评估这两种药物的协同作用。

方法与结果

提取2016年至2018年多中心数据库中的患者数据。患者分为：（1）同时治疗组：在6周内同时开具伊伐布雷定和沙库巴曲缬沙坦；（2A）序贯治疗组，伊伐布雷定优先：先开具伊伐布雷定，随后开具沙库巴曲缬沙坦；（2B）序贯治疗组，沙库巴曲缬沙坦优先：先开具沙库巴曲缬沙坦，随后开具伊伐布雷定。共纳入464例HFrEF患者。心血管死亡和/或因心力衰竭计划外再次住院的情况较少见（28.6%对44.8%，P = 0.01），同时治疗组患者左心室射血分数（LVEF）的改善显著大于序贯治疗组（LVEF变化12.8±12.9%对9.3±12.6%，P = 0.007）。在序贯治疗亚组中，与沙库巴曲缬沙坦优先治疗相比，伊伐布雷定优先治疗降低心率并升高收缩压（SBP）（心率变化-9.1±12.9次/分钟对2.6±16.0次/分钟，P < 0.001；SBP变化4.6±16.5 mmHg对-4.8±17.2 mmHg，P < 0.001），而沙库巴曲缬沙坦优先治疗的LVEF改善程度更高（LVEF变化3.6±7.8%对0.7±7.7%，P = 0.002）。随访结束时，两个序贯治疗亚组之间的SBP、LVEF和左心室容积相当。