Efficacy of early initiation of ivabradine treatment in patients with acute heart failure: rationale and design of SHIFT-AHF trial

Abstract

Aims: Elevated heart rate (HR) in heart failure (HF) is associated with worse outcomes, particularly in acute HF (AHF). HR reduction with ivabradine reduces cardiovascular events in HF patients with reduced ejection fraction. The present trial aimed to test the hypothesis that the early HR reduction using ivabradine improves clinical outcomes in patients with AHF.

Methods and results: SHIFT-AHF is a prospective, multi-centre, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of ivabradine when adding to standard therapy in AHF patients (SHIFT-AHF). The trial will include 674 AHF patients with left ventricular ejection fraction < 45% and New York Heart Association functional classes III-IV. Participants were enrolled from March 2020 and will be followed up until December 2022. Patients are randomized to treatment with ivabradine or placebo (randomization 1:1). After allocation, the dose of ivabradine is titrated according to HR. Six months' follow-up and three control visits (7, 90, and 180 days after enrolment) are required for every participant. Assessment involves clinical examination, laboratory tests, echocardiography, electrocardiography, heart rhythm, cardiac function, and quality of life. The primary endpoint is a composite of all-cause mortality or re-admission due to worsening HF. Secondary endpoints include the assessments of cardiac remodelling, cardiac functional capacity, and quality of life.

Conclusions: The SHIFT-AHF trial will shed further light on the role of early HR reduction using ivabradine in patients with AHF.

Keywords: Acute heart failure; Ivabradine; Outcomes; Randomized controlled trial.

FIGURE 1

Flow chart of SHIFT‐AHF trial. ACS, acute coronary syndrome; TIA, transient ischaemic attack.

FIGURE 2

Outline of SHIFT‐AHF trial. After the enrolment is complete, patients are randomly allocated to either interventional group or control group. STAHF is given to both groups, while ivabradine or placebo is given on top of STAHF to patients according to allocation. Ivabradine or placebo treatment is started at D0 visit. The starting dose is 5 mg twice daily. Resting heart rate (RHR) of participants should be re‐evaluated after 24 h (D2). If the RHR is more than 70 b.p.m., the dose should be maintained. The dose will be decreased to 2.5 mg twice daily if RHR is <70 b.p.m.. Once the RHR is <60 b.p.m. or the symptoms related with bradycardia appear, ivabradine or placebo should be stopped The third, fourth, and fifth heart rate assessments are arranged at D7 visit, D90 visit, and D180 visit, respectively. AHF, acute heart failure; RHR, resting heart rate; STAHF, standard therapy in acute heart failure.