Heart rate reduction and outcomes in heart failure outpatients

Abstract

Abstract Aim Pharmacologic reduction of heart rate (HR) with beta blockers (BB) and/or ivabradine has been associated with improved survival in patients with heart failure (HF) in sinus rhythm. We analyzed the impact of different HR-reducing drug treatments on outcomes in a cohort of outpatients with heart failure (HF). Methods Consecutive patients with HF and sinus rhythm (SR) referred to a specialized tertiary HF service offering advanced therapy options including assist device and heart transplantation were prospectively enrolled from August 2015 until March 2018. Clinical characteristics were assessed at baseline. We performed Cox regression analyses to examine the effect of the resting HR and the drug regimen (BB in submaximal dose [group 1], BB in maximum tolerated dose [group 2], or BB in maximum tolerated dose plus ivabradine [group 3]) on all-cause mortality and a combined, disease-related endpoint of "death from any cause or heart transplantation". Results Of 278 patients included, 213 (76.6%) were male. Median age was 57.0 years (interquartile range 49.0-66.1). HF was due to non-ischemic origin in 167 patients (60.1%). HFrEF was present in 185 patients (73.7%). There was a decent use of guideline-recommended HF medication (MRA in 82%, RAS blocker [ARNI/ACEI/ARB] in 97%). Most patients received treatment with a BB in submaximal [n = 118, group 1], or maximum tolerated dose [n = 136, group 2]. Patients treated with BB in maximum tolerated dose plus ivabradine [n = 24, group 3] were younger (53.0 vs. 58.0 years) and had a lower left-ventricular ejection fraction on echocardiography (EF, 25 vs. 31%) than those without ivabradine. Over a mean follow-up period of 3.1 years, 30 patients died, and 11 underwent heart transplantation. Upon regression analyses, higher resting HR was associated with an increased risk of death or heart transplantation (hazard ratio HR 1.03 [1.01, 1.06], p = 0.0072, even after adjusting for age and sex. Neither the type of heart rate-reducing therapy (BB with or without ivabradine), nor the dose of BB or ivabradine affected outcome. Conclusion Our prospective study underlines the importance of heart rate reduction in HF with SR but failed to demonstrate a better risk reduction in patients with up-titrated BB doses or on a combination of BB plus ivabradine.Study profileKM-curves for the composite endpoint