Swedberg K. Lancet. 2010 Sep 11;376(9744):875-85.
Chronic heart failure is correlated with high mortality and morbidity. Elevated resting heart rate is a risk factor for adverse consequences. Risk of death, cardiovascular death, or admission to hospital in patients with heart failure is directly related to heart rate, and heart-rate reduction exhibits favorable outcomes. Despite, the use of β-blockers, heart rate still remains elevated, which suggests a further reason to look for new therapeutic strategies. Thus, Swedberg K et al., conducted a study to examine the effect of heart-rate reduction on consequences in heart failure by the selective sinus-node inhibitor Ivabradine.
Patients with symptomatic heart failure and a left-ventricular ejection fraction of 35% or lower, were in sinus rhythm with heart rate 70 beats per min or higher, hospitalisation for heart failure within the previous year, and on stable background treatment including a β-blocker were eligible for participation in this randomised, double-blind, placebo-controlled, parallel-group study. Patients were randomly allocated to Ivabradine titrated to a maximum of 7·5 mg twice daily or matching placebo by computer-induced distribution schedule. Treatment allocation was concealed to patients and investigators.
Composite of cardiovascular death or hospital admission for worsening heart failure constituted the primary outcomes. Analysis was done by intention to treat. 6558 patients were randomly allocated to treatment groups (3268 Ivabradine, 3290 placebo). Data were available for 3241 patients in the Ivabradine group and 3264 patients in the placebo for analysis. Median follow-up was done for 22·9 (IQR 18–28) months.
Ivabradine group showed significant reduction in the primary endpoint event as compared to placebo group [793 (24%) vs. 937 (29%)] (HR 0·82, 95% CI 0·75–0·90, p<0·0001) and in hospital admissions for worsening heart failure (514 [16%] vs 672 [21%]; HR 0·74, 0·66–0·83; p<0·0001). (Figure 1)
Figure 1: Kaplan-Meier cumulative event curves for (A) the primary composite endpoint of cardiovascular death or hospital admission for worsening heart failure, (B) hospital admission for worsening heart failure
Ivabradine exhibited significant reduction in deaths due to heart failure (113 [3%] vs 151 [5%]; HR 0·74, 0·58–0·94, p=0·014) and all cause death (503 [16%] vs 552 [17%]; HR 0·90 (95% CI 0·80–1·02), p=0·092. (Figure 2)
Figure 2: Kaplan-Meier cumulative event curves for (A) death from heart failure and (B) all-cause death
Thus, it was concluded that Ivabradine has an important role in reduction of heart rate for favourable outcomes in heart failure and the study also confirms the significant role of heart rate in the pathophysiology of heart failure.
