Effect of Ivabradine on Recurrent Hospitalization for Worsening Heart Failure in Patients With Chronic Systolic Heart Failure: The SHIFT Study

Study Questions:

Does ivabradine reduce admissions for worsening heart failure (HF)?


This was a secondary analysis of the SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) study, which was a double-blind, randomized trial of ivabradine 5 mg twice daily (titrated based on heart rate and tolerability) versus placebo administered to patients with systolic HF (ejection fraction ≤35%). Patients with heart rates <70 bpm or who were not in sinus rhythm were excluded. The endpoint of interest was rehospitalization for HF exacerbation.


Of 6,505 patients randomized, 1,186 (18%) patients had at least one HF hospitalization (hospitalization frequency: once in 714 patients, twice in 254, three times in 218 patients) during a mean 22.9 months of follow-up. Patients with more frequent hospitalizations were older, with lower systolic blood pressure, lower left ventricular ejection fraction, a greater burden of New York Heart Association (NYHA) class III/IV, and more comorbidities (e.g., diabetes, atrial fibrillation). The incidence rate (IR) for HF hospitalization in patients treated with ivabradine (902 hospitalizations) was lower than that of placebo (1,211 hospitalizations, IR ratio 0.75 [0.65-0.87]). The unadjusted risk of having a second (hazard ratio, 0.66 [0.55-0.70]) or third (hazard ratio, 0.71 [0.54-0.93]) HF hospitalization was also lower in ivabradine-treated patients. Patients treated with ivabradine had more days alive and out of the hospital (by 13 days, p = 0.005) than placebo-treated patients.


The authors concluded that patients with systolic HF treated with ivabradine had fewer HF hospitalizations.


Ivabradine inhibits the sinoatrial If current, leading to a dose-dependent slowing of heart rate. It is approved for use in NYHA class II-IV systolic HF in Europe. In this secondary analysis of SHIFT, ivabradine was added to standard evidence-based therapy, leading to a reduction in HF hospitalization that was apparent up to 36 months after drug initiation. It has been quite some time since the HF community has been afforded a new therapy for patient management. While a reduction in HF hospitalization is an important endpoint, we also need to see either a reduction in mortality or no mortality increase over long-term follow-up. The drug appeared to afford no increased events in the primary analysis.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Follow-Up Studies, Chronic Disease, Blood Pressure, Europe, New York, Benzazepines, Heart Diseases, Incidence, Cardiology, Heart Failure, Stroke Volume, Diabetes Mellitus

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