title: Uptitration of renin-angiotensin system blocker and beta-blocker therapy in patients hospitalized for heart failure with reduced versus preserved left ventricular ejection fractions.
abstract: In ambulatory patients with heart failure (HF) and reduced ejection fraction (rEF), renin-angiotensin system (RAS) and β-blockers at guideline-recommended target dose reduce all-cause mortality and readmissions. Benefits in HF with preserved ejection fraction (pEF), as well as uptitration after a hospitalization, remain uncertain. This study assesses the impact of RAS- and β-blocker uptitrations in patients with HFrEF versus HFpEF during and immediately after a hospital admission. In consecutive patients (209 HFrEF with left ventricular ejection fraction <40% and 108 HFpEF with left ventricular ejection fraction ≥40%), RAS- and β-blocker dose changes were followed during 6 months after an index HF hospitalization. Patients with a RAS- and β-blocker dose increase of ≥10% of the recommended target dose were compared with patients without uptitration. Patients who received uptitration were significantly younger, with a higher heart rate and better renal function, and received spironolactone more often. Both RAS- and β-blocker uptitrations were associated with significant reductions in the composite end-point of all-cause mortality or HF readmissions in HFrEF (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.22 to 0.60 and HR 0.51, 95% CI 0.32 to 0.81, respectively). After correction for age, heart rate, blood pressure, renal function, and spironolactone use, this association remained significant for RAS blockers (HR 0.54, 95% CI 0.31 to 0.93, p = 0.027) but not for β-blockers (HR 0.65, 95% CI 0.39 to 1.09, p = 0.101). No benefit of RAS- or β-blocker uptitration was observed in HFpEF. In conclusion, uptitration of neurohumoral blockers after an HF hospitalization is more frequently performed in younger patients with low co-morbidity burden. RAS-blocker uptitration independently predicts clinical outcome in patients with HFrEF but not in those with HFpEF.
authors.affiliation: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine & Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Frederik H
authors.initials: FH
authors.lastname: Verbrugge
authors.forename: Jürgen
authors.initials: J
authors.lastname: Duchenne
authors.forename: Philippe B
authors.initials: PB
authors.lastname: Bertrand
authors.forename: Matthias
authors.initials: M
authors.lastname: Dupont
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.forename: Wilfried
authors.initials: W
authors.lastname: Mullens
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D058406:Cardiac Resynchronization Therapy; D003131:Combined Modality Therapy; D015897:Comorbidity; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013148:Spironolactone / Q000008:administration & dosage; D013318:Stroke Volume; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D013148:Spironolactone