Implications of Using Different Definitions on Outcomes in Worsening Heart Failure

Abstract

Background: In-hospital worsening heart failure (WHF) is an important event that has inconsistent definitions used across trials. We used data from 2 acute heart failure (HF) trials from the National Institutes of Health HF Network, DOSE (Diuretic Optimization Strategies Evaluation) and ROSE (Renal Optimization Strategies), to understand event rates associated with different WHF definitions.

Methods and results: We pooled data from 668 patients in DOSE and ROSE and assessed the relationship between WHF and the composite end point of rehospitalization, emergency room visits for HF, and mortality through 60 days. We also assessed for a differential relationship between the timing of WHF development and outcomes. The overall incidence of WHF was 14.6% (24.1% in DOSE, 6.3% in ROSE, and 5.0% in DOSE using the ROSE definition). WHF was associated with an increase in the composite end point (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.11-2.42; P=0.01). However, the association between WHF and outcomes was significantly stronger in ROSE than in DOSE (HR, 2.67; 95% CI, 1.45-4.91; P<0.01 and HR, 1.28; 95% CI, 0.79-2.08; P=0.31, respectively). Development of WHF between baseline to 24 hours compared with 24 to 48 hours or 48 to 72 hours demonstrated a trend toward improved outcomes (HR, 0.49; 95% CI, 0.21-1.17; P=0.11 and HR, 0.45; 95% CI, 0.20-1.04; P=0.06, respectively).

Conclusions: A WHF definition that excluded the intensification of diuretics resulted in a lower event rate but a stronger association with outcomes. These data support the need for continued efforts to standardize WHF definitions in clinical trials.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00577135 (DOSE) and NCT01132846 (ROSE).

Keywords: diuretics; heart failure; hospitalization; outcome assessment (health care).

© 2016 American Heart Association, Inc.

Figures

Figure 1

Flow chart of patients in ROSE and DOSE who were analyzed in this analysis. 668 patients were available for analysis with 22 total patients excluded. 4 patients were excluded because of duplicate participation and 18 patients were excluded because there was no ascertainment of WHF.

Figure 2

Forrest Plot of the pooled and individual ROSE and DOSE clinic trials demonstrating the Hazard Ratio of developing WHF compared with no development of WHF with outcomes of 60 Day death, HF Rehospitalization and ER visit for HF.

Figure 3

Forrest Plot of the pooled and individual ROSE and DOSE clinic trials demonstrating the Hazard Ratio of developing WHF between baseline and 24–72 hours with outcomes of 60 Day death, HF Rehospitalization and ER visit for HF.