The Hospitalization Burden and Post-Hospitalization Mortality Risk in HeartFailure With Preserved EjectionFraction: Results From the I-PRESERVE Trial (Irbesartan in HeartFailureand Preserved Ejection Fraction)

Peter E. Carson, Inder S. Anand, Sithu Win, Thomas Rector, Markus Haass, Jose Lopez-Sendon, Alan Miller, John R. Teerlink, Michel White, Robert S. McKelvie, Michel Komajda, Michael R. Zile, John J. McMurray, Barry Massie

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Objectives: The aim of this study was to investigate prognosis in patients with heart failure (HF) with preserved ejection fraction and the causes of hospitalization and post-hospitalization mortality. Background: Although hospitalizations in patients with HF with preserved ejection fraction are common, there are limited data from clinical trials on the causes of admission and the influence of hospitalizations on subsequent mortalityrisk. Methods: Patients (n= 4,128) with New York Heart Association functional class II to IV HF and left ventricular ejection fractions >45% were enrolled in I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction). A blinded events committee adjudicated cardiovascular hospitalizations and all deaths using predefined and standardized definitions. The risk for death after HF, any-cause, or non-HF hospitalization was assessed using time-dependent Cox proportional hazard models. Results: A total of 2,278 patients had 5,863 hospitalizations during the 49 months of follow-up, of which 3,585 (61%) were recurrent hospitalizations. For any-cause hospitalizations, 26.5% of patients died during follow-up, with an incident mortality rate of 11.1 deaths per 100 patient-years (PYs) and an adjusted hazard ratio of 5.32 (95% confidence interval: 4.21 to 6.23). Overall, 53.6% of hospitalizations were classified as cardiovascular and 43.7% as noncardiovascular, with 2.7% not classifiable. HF was the largest single cause of initial (17.6%) and overall (21.1%) hospitalizations, although, after HF hospitalization, a substantially higher proportion of readmissions were due to primary HF causes (40%). HF hospitalization occurred in 685 patients, with 41% deaths during follow-up, an incident mortality rate of 19.3 deaths per 100 PYs. The adjusted hazard ratio was 2.93 (95% confidence interval: 2.40 to 3.57) relative to patients who were not hospitalized for HF and was greater in those with longer durations of hospitalization. There were 1,593 patients with only non-HF hospitalizations, 21% of whom died during follow-up, with an incident mortality rate of 8.7 deaths per 100 PYs and an adjusted hazard ratio of 4.25 (95% confidence interval: 3.27 to 5.32). The risk for death was highest in the first 30days and declined over time for all hospitalization categories. Patients not hospitalized for HF or for any cause had observed incident mortality rates of 3.8 and 1.3 deaths per 100 PYs, respectively. Conclusions: In I-PRESERVE, HFpEF patients hospitalized for any reason, and especially for HF, were at high risk for subsequent death, particularly early. The findings support the need for careful attention in the post-discharge time period including attention to comorbid conditions. Among those hospitalized for HF, the high mortality rate and increased proportion of readmissions due to HF (highest during the first 30 days), suggest that this group would be an appropriate target for investigation of new interventions.

Original languageEnglish (US)
Pages (from-to)429-441
Number of pages13
JournalJACC: Heart Failure
Issue number6
StatePublished - Jun 1 2015

Bibliographical note

Funding Information:
Bristol-Myers Squibb sponsored the I-PRESERVE trial. The views expressed herein do not necessarily represent the views of the U.S. Department of Veterans Affairs or the U.S. government. Dr. Rector was supported by resources and facilities of the Minneapolis Veterans Affairs Health Care System . Drs. Carson, Anand, Haass, Lopez-Sendon, Miller, Teerlink, White, McKelvie, Komajda, Zile, McMurray, and Massie were consultants to Bristol-Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2015 American College of Cardiology Foundation.


  • Heart failure
  • Hospitalizations
  • Preserved ejection fraction
  • Prognosis


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