Abstract：
Quadruple therapy is effective for patients with heart failure with reduced ejection fraction, providing significant clinical benefits, including reduced mortality. Clinicians are now in an era focused on how to initiate and titrate quadrable therapy in the early phase of the disease trajectory, including during heart failure hospitalization. However, patients with heart failure with reduced ejection fraction still face a significant \"residual risk\" of mortality and heart failure hospitalization. Despite the effective implementation of quadruple therapy, high mortality and rehospitalization rates persist in heart failure with reduced ejection fraction, and many patients cannot maximize therapy due to side effects such as hypotension and renal dysfunction. In this context, ivabradine, vericiguat, and omecamtiv mecarbil may have adjunct roles in addition to quadruple therapy (note that omecamtiv mecarbil is not currently approved for clinical use). However, the contemporary use of ivabradine and vericiguat is relatively low globally, likely due in part to the under-recognition of the role of these therapies as well as costs. This review offers clinicians a straightforward guide for bedside evaluation of potential candidates for these medications. Quadruple therapy, with strong evidence to reduce mortality, should always be prioritized for implementation. As second-line therapies, ivabradine could be considered for patients who cannot achieve optimal heart rate control (≥ 70 bpm at rest) despite maximally tolerated beta-blocker dosing. Vericiguat could be considered for high-risk patients who have recently experienced worsening heart failure events despite being on quadrable therapy, but they should not have N-terminal pro-B-type natriuretic peptide levels exceeding 8000 pg/mL. In the future, omecamtiv mecarbil may be considered for severe heart failure (New York Heart Association class III to IV, ejection fraction ≤ 30%, and heart failure hospitalization within 6 months) when current quadrable therapy is limited, although this is still hypothesis-generating and requires further investigation before its approval.
摘要：
四联疗法对射血分数降低的心力衰竭患者有效，提供显著的临床益处，包括降低死亡率。临床医生现在正处于一个专注于如何在疾病轨迹的早期阶段启动和滴定象限治疗的时代，包括心力衰竭住院期间。然而,射血分数降低的心力衰竭患者仍面临死亡和心力衰竭住院的显著"残余风险".尽管四联疗法得到了有效的实施，高死亡率和再住院率在射血分数降低的心力衰竭中持续存在，许多患者由于低血压和肾功能不全等副作用而无法最大限度地治疗。在这种情况下，伊伐布雷定,Vericiguat,和omecamtivmecarbil除了四联疗法外，还可能具有辅助作用（请注意，omecamtivmecarbil目前尚未批准用于临床）。然而,伊伐布雷定和维利吉瓜的当代使用量在全球范围内相对较低，可能部分原因是对这些疗法的作用和成本的认识不足。这篇综述为临床医生提供了直接的指导，用于床边评估这些药物的潜在候选药物。四重疗法,有强有力的证据可以降低死亡率，应始终优先执行。作为二线疗法，对于尽管β受体阻滞剂的最大耐受剂量仍无法达到最佳心率控制（静息时≥70bpm）的患者，可以考虑伊伐布雷定。Vericiguat可以考虑用于高风险患者，尽管正在接受正交治疗，但最近经历了恶化的心力衰竭事件，但其N末端B型利钠肽前体水平不应超过8000pg/mL.在未来,omecamtivmecarbil可考虑用于严重心力衰竭（纽约心脏协会III至IV级，射血分数≤30%,和心力衰竭住院在6个月内），当目前的象限治疗是有限的，尽管这仍然是假设产生的，在批准之前需要进一步调查。
