Selective Heart Rate Reduction With Ivabradine and LV Remodelling
Selective Heart Rate Reduction With Ivabradine and LV Remodelling
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; 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, 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/m) 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.
Cardiac remodelling is central to the pathophysiology of heart failure (HF) and is an established prognostic factor in patients with HF. Left ventricular (LV) enlargement has been shown to be associated with an increased risk for adverse cardiac events, while reduced LV ejection fraction (LVEF) is a powerful predictor of cardiovascular outcomes and all-cause mortality. The therapeutic effects of beta-blockade, angiotensin-converting enzyme (ACE) inhibition, and cardiac resynchronization therapy have been linked to their beneficial effects on cardiac remodelling. A recent analysis compared 30 clinical event trials and 88 remodelling trials with the same drug or device therapy and reported that the odds ratio associated with therapy for long-term mortality correlate with the shorter term effect of the therapy on LVEF, end-systolic volume, and end-diastolic volume. It is therefore relevant to evaluate the impact of novel HF therapies on cardiac remodelling.
The heart rate lowering effect of ivabradine, a specific inhibitor of the If current in the sinoatrial node, has been found to be beneficial in patients with HF. The results of the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) showed that treatment with ivabradine superimposed on background therapy for HF was associated with an 18% reduction in risk for the primary composite endpoint of cardiovascular death or hospitalization for worsening HF (P< 0.0001). In this article, we present the results of the prespecified echocardiographic substudy of the SHIFT trial, aiming to evaluate the effects of ivabradine vs. placebo on LV remodelling and function in HF.
Abstract and Introduction
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; 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, 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/m) 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.
Introduction
Cardiac remodelling is central to the pathophysiology of heart failure (HF) and is an established prognostic factor in patients with HF. Left ventricular (LV) enlargement has been shown to be associated with an increased risk for adverse cardiac events, while reduced LV ejection fraction (LVEF) is a powerful predictor of cardiovascular outcomes and all-cause mortality. The therapeutic effects of beta-blockade, angiotensin-converting enzyme (ACE) inhibition, and cardiac resynchronization therapy have been linked to their beneficial effects on cardiac remodelling. A recent analysis compared 30 clinical event trials and 88 remodelling trials with the same drug or device therapy and reported that the odds ratio associated with therapy for long-term mortality correlate with the shorter term effect of the therapy on LVEF, end-systolic volume, and end-diastolic volume. It is therefore relevant to evaluate the impact of novel HF therapies on cardiac remodelling.
The heart rate lowering effect of ivabradine, a specific inhibitor of the If current in the sinoatrial node, has been found to be beneficial in patients with HF. The results of the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) showed that treatment with ivabradine superimposed on background therapy for HF was associated with an 18% reduction in risk for the primary composite endpoint of cardiovascular death or hospitalization for worsening HF (P< 0.0001). In this article, we present the results of the prespecified echocardiographic substudy of the SHIFT trial, aiming to evaluate the effects of ivabradine vs. placebo on LV remodelling and function in HF.
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