Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Study

Abstract

Aims: We explored the effect of treatment with ivabradine, a pure heart rate-slowing agent, on recurrent hospitalizations for worsening heart failure (HF) in the SHIFT trial.

Methods and results: SHIFT was a double-blind clinical trial in which 6505 patients with moderate-to-severe HF and left ventricular systolic dysfunction, all of whom had been hospitalized for HF during the preceding year, were randomized to ivabradine or to placebo on a background of guideline-recommended HF therapy (including maximized β-blockade). In total, 1186 patients experienced at least one additional HF hospitalization during the study, 472 suffered at least two, and 218 suffered at least 3. Patients with additional HF hospitalizations had more severe disease than those without. Ivabradine was associated with fewer total HF hospitalizations [902 vs. 1211 events with placebo; incidence rate ratio, 0.75, 95% confidence interval (CI), 0.65-0.87, P = 0.0002] during the 22.9-month median follow-up. Ivabradine-treated patients evidenced lower risk for a second or third additional HF hospitalization [hazard ratio (HR): 0.66, 95% CI, 0.55-0.79, P < 0.001 and HR: 0.71, 95% CI, 0.54-0.93, P = 0.012, respectively]. Similar observations were made for all-cause and cardiovascular hospitalizations.

Conclusion: Treatment with ivabradine, on a background of guidelines-based HF therapy, is associated with a substantial reduction in the likelihood of recurrent hospitalizations for worsening HF. This benefit can be expected to improve the quality of life and to substantially reduce health-care costs.

Figure 1

Cumulative incidence of hospitalizations for worsening heart failure (mean number of events per patient) during the study. IRR, incidence rate ratio. CI, confidence interval. *Estimate of rate of hospitalizations over time (corrected for the competing risk of death).

Figure 2

Estimate of treatment effect on recurrence of hospitalizations for worsening heart failure (total-time approach). The approach allows for a cumulative effect in which the second hospitalization includes the effect of the first, and the third hospitalization includes the effects of the first and second. All data adjusted for prognostic factors at the baseline (β-blocker, New York Heart Association class, left ventricular ejection fraction, ischaemic cause of heart failure, age, systolic blood pressure, heart rate, and creatinine clearance).