Effects of selective heart rate reduction with ivabradine on left ventricular remodelling and function: results from the SHIFT echocardiography substudy

Jean-Claude Tardif, Eileen O'Meara, Michel Komajda, Michael Böhm, Jeffrey S Borer, Ian Ford, Luigi Tavazzi, Karl Swedberg, SHIFT Investigators, Jean-Claude Tardif, Eileen O'Meara, Michel Komajda, Michael Böhm, Jeffrey S Borer, Ian Ford, Luigi Tavazzi, Karl Swedberg, SHIFT Investigators

Abstract

Aims: The SHIFT echocardiographic substudy evaluated the effects of ivabradine on left ventricular (LV) remodelling in heart failure (HF).

Methods and results: Eligible patients had chronic HF and systolic dysfunction [LV ejection fraction (LVEF) ≤35%], were in sinus rhythm, and had resting heart rate ≥70 bpm. Patients were randomly allocated to ivabradine or placebo, superimposed on background therapy for HF. Complete echocardiographic data at baseline and 8 months were available for 411 patients (ivabradine 208, placebo 203). Treatment with ivabradine reduced LVESVI (primary substudy endpoint) vs. placebo [-7.0 ± 16.3 vs. -0.9 ± 17.1 mL/m(2); difference (SE), -5.8 (1.6), 95% CI -8.8 to -2.7, P< 0.001]. The reduction in LVESVI was independent of beta-blocker use, HF aetiology, and baseline LVEF. Ivabradine also improved LV end-diastolic volume index (-7.9 ± 18.9 vs. -1.8 ± 19.0 mL/m(2), P= 0.002) and LVEF (+2.4 ± 7.7 vs. -0.1 ± 8.0%, P< 0.001). The incidence of the SHIFT primary composite outcome (cardiovascular mortality or hospitalization for worsening HF) was higher in patients with LVESVI above the median (59 mL/m2) at baseline (HR 1.62, 95% CI 1.03-2.56, P= 0.04). Patients with the largest relative reductions in LVESVI had the lowest event rates.

Conclusion: Ivabradine reverses cardiac remodelling in patients with HF and LV systolic dysfunction.

Figures

Figure 1
Figure 1
Trial profile. FAS, full analysis set.
Figure 2
Figure 2
(A) Relative change in left ventricular end-systolic volume index (LVESVI) and (B) absolute change in left ventricular ejection fraction (LVEF) from baseline to 8 months. The grey and white bars represent percentages of patients reaching echocardiographic criteria for the ivabradine and placebo groups, respectively.
Figure 3
Figure 3
Kaplan–Meier cumulative event curves for the SHIFT primary composite endpoint of cardiovascular death or hospitalization for worsening heart failure in the placebo group split by median left ventricular end-systolic volume index (LVESVI) ≥59 vs. 2.

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