Worsening Heart Failure Following Admission for Acute Heart Failure A Pooled Analysis of the PROTECT and RELAX-AHF Studies

Beth A. Davison, Marco Metra, Gad Cotter, Barry M. Massie, John G. F. Cleland, Howard C. Dittrich, Christopher Edwards*, Gerasimos Filippatos, Michael M. Givertz, Barry Greenberg, Piotr Ponikowski, Adriaan A. Voors, Christopher M. O'Connor, John R. Teerlink, PROTECT & RELAX-AHF Executive Comm

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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OBJECTIVES These studies conducted analyses to examine patient characteristics and outcomes associated with worsening heart failure (WHF).

BACKGROUND WHF during an admission for acute heart failure (AHF) represents treatment failure and is a potential therapeutic target for clinical trials of AHF.

METHODS Individual patient data from the PROTECT (Placebo-Controlled Randomized Study of the Selective A(1) Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Relaxin in Acute Heart Failure) phase II and III studies were pooled for analysis.

RESULTS Of 3,691 patients, death or WHF through day 5 occurred in 12.4%, ranging from 9.5% to 14.5% among studies. A multivariable model provided modest discrimination between patients who did or did not develop WHF (C-index = 0.68). After multivariable adjustment, WHF was associated with a mean increase in length of stay of 5.2 days (95% confidence interval [CI]: 4.6 to 5.8 days) and increased risks of 60-day HF or renal failure readmission or cardiovascular death (hazard ratio [HR]: 1.64, 95% CI: 1.34 to 2.01) and 180-day mortality (HR: 1.93, 95% CI: 1.55 to 2.41) (all p <0.001). The risk of mortality was higher in patients whose WHF required intravenous inotropes or mechanical therapy (HR: 3.03, 95% CI: 2.11 to 4.36) compared with patients whose WHF was treated with intravenous loop diuretic alone (HR: 1.80, 95% CI: 1.36 to 2.36) (both p <0.001). WHF was associated with larger increases in markers of renal and hepatic dysfunction during the first days of admission, but remained significantly associated with adverse outcomes after adjustment for these changes.

CONCLUSIONS WHF during the first 5 days of admission for AHF occurred in approximately 10% to 15% of patients and was associated with longer length of stay and higher risk for readmission and death. (C) 2015 by the American College of Cardiology Foundation.

Original languageEnglish
Pages (from-to)395-403
Number of pages9
JournalJACC. Heart failure
Issue number5
Publication statusPublished - May-2015


  • acute heart failure
  • heart failure readmission
  • mortality
  • prognosis
  • renal function
  • worsening heart failure

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