Can ivabradine reduce NT-proBNP and improve outcomes in systolic heart failure?

Article p. 501 Ivabradine selectively reduces heart rate (HR) by inhibiting If of the sinus node. The BEAUTIFUL trial has shown that ivabradine is ‘beneficial’ in patients who suffered from coronary artery disease (CAD) with systolic heart failure (HF) (ejection fraction [EF] 32%) without evidence of overt HF. Added to standard therapy ivabradine did not significantly the primary composite endpoint (admission to hospital for new onset or worsening HF, admission to hospital for acute myocardial infarction or cardiovascular death); however, in a subgroup of patients with baseline HR > 70 bpm (mean 79 bpm) ivabradine significantly decreased (–36%) the risk for fatal and non-fatal acute myocardial infarction, and (–30%) the risk of coronary revascularization [1]. In the SHIFT trial patients with systolic HF (EF 70 bpm, and who received optimized background therapy according to guideline recommendations were treated with ivabradine or placebo. A higher HR ≥ 75 bpm at entry, there was a significant reduction in the cardiovascular death and all-cause mortality endpoints [2]. Patients on ivabradine with an HR reduction (11 bpm) had an 18% decrease of composite endpoint; this result was primarily driven by a reduction (–26%) in hospital admissions for worsening HF [3, 4]. In patients with HF, due to ischemic etiology with left ventricular diastolic dysfunction and preserved systolic function ivabradine is poorly effective [5]. Importantly, in the SIGNIFY trial, in patients who had stable CAD (Canadian Cardiovascular Society [CCS] class ≥ 2) without clinical HF, and who were treated with guideline-recommended medical therapy, the addiction of ivabradine did not improve the outcome; furthermore, adverse events occurred statistically (p < 0.001 for all class comparisons) more frequently with ivabradine than with placebo [6]. Adverse events led to studydrug withdrawal in 13.2% of the ivabradine-group and in 7.4% of the placebo group (p < 0.001) [2]. Ivabradine significantly increased the frequency of symptomatic bradycardia, atrial fibrillation and phosphenes.