Relationship between heart rate and mortality and morbidity in the irbesartan patients with heart failure and preserved systolic function trial (I-Preserve)

Eur J Heart Fail. 2014 Jul;16(7):778-87. doi: 10.1002/ejhf.85. Epub 2014 May 23.

Abstract

Background: Higher heart rate is associated with poorer outcomes in patients with heart failure and reduced ejection fraction (HF-REF). Less is known about the association between heart rate and outcomes in patients with heart failure and preserved ejection fraction (HF-PEF). Therefore, we examined the relationship between heart rate and outcomes in the irbesartan in patients with heart failure and preserved systolic function trial (I-Preserve) in patients with an ejection fraction >45% aged >60 years.

Methods and results: Heart rate was analysed as both a categorical (tertiles) and continuous variable. Patients in sinus rhythm (n = 3271) and atrial fibrillation (n = 696) were analysed separately. The outcomes examined were the primary endpoint of the trial (all-cause death or cardiovascular hospitalization), the composite of cardiovascular death or heart failure hospitalization (and its components) and all-cause death alone. Higher heart rate was associated with a significantly higher risk of all outcomes studied for patients in sinus rhythm, even after adjustment for other prognostic variables, including N-terminal pro-B-type natriuretic peptide. Each standard deviation (12.4 bpm) increase in heart rate was associated with an increase in risk of 13% for cardiovascular death or heart failure hospitalization (P = 0.002). No relationship between heart rate and outcomes was observed for patients in atrial fibrillation. Beta-blocker treatment did not reduce the heart rate-risk relationship.

Conclusions: In patients with heart failure and preserved ejection fraction, heart rate is in sinus rhythm an independent predictor of adverse clinical outcomes and might be a therapeutic target in this syndrome. Clinical Trial Registration - URL http://www.clinicaltrials.gov. Unique identifier: NCT 0095238.

Trial registration: ClinicalTrials.gov NCT00095238.

Keywords: Heart failure; Heart rate; Irbesartan; Morbidity; Mortality.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Atrial Fibrillation / mortality
  • Atrial Fibrillation / physiopathology*
  • Biphenyl Compounds / therapeutic use
  • Female
  • Heart Failure / drug therapy
  • Heart Failure / mortality
  • Heart Failure / physiopathology*
  • Heart Rate / physiology*
  • Hospitalization / statistics & numerical data*
  • Humans
  • Irbesartan
  • Male
  • Middle Aged
  • Prognosis
  • Stroke Volume
  • Tetrazoles / therapeutic use
  • Ventricular Dysfunction, Left / drug therapy
  • Ventricular Dysfunction, Left / mortality
  • Ventricular Dysfunction, Left / physiopathology*

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin II Type 1 Receptor Blockers
  • Biphenyl Compounds
  • Tetrazoles
  • Irbesartan

Associated data

  • ClinicalTrials.gov/NCT00095238