Influence of previous heart failure hospitalization on cardiovascular events in patients with reduced and preserved ejection fraction

Abstract

Background: Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between previous HF hospitalization and randomization in the Candesartan in Heart failure: Reduction in Mortality and morbidity (CHARM) trials on clinical outcomes in patients with both reduced and preserved ejection fraction.

Methods and results: CHARM enrolled 7599 patients with New York Heart Association class II to IV HF, of whom 5426 had a history of previous HF hospitalization. Cox proportional hazards regression models were used to assess the association between time from previous HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF during a median of 36.6 months. For patients with HF and reduced or preserved ejection fraction, rates of cardiovascular mortality and HF hospitalization were higher among patients with previous HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for patients with HF and reduced ejection fraction within each category. Event rates for those with HF with preserved ejection fraction and a HF hospitalization in the 6 months before randomization were comparable with the rate in patients with HF and reduced ejection fraction with no previous HF hospitalization.

Conclusions: Rates of cardiovascular death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high-risk population for future clinical trials in HF and reduced ejection fraction and HF with preserved ejection fraction.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT00634400.

Keywords: clinical trials; heart failure; hospitalization; outcomes assessment.

Figure 1

Prior hospitalization for heart failure is associated with increased risk of CV death and HF hospitalization independent of EF.

Figure 2

A. Increasing rates of CV death and HF hospitalization with more recent hospitalization prior to enrollment. B. Mortality rates increase as time between prior hospitalization and enrollment decreases.

Figure 2

A. Increasing rates of CV death and HF hospitalization with more recent hospitalization prior to enrollment. B. Mortality rates increase as time between prior hospitalization and enrollment decreases.

Figure 3

Time to death or second heart failure hospitalization following an in-trial heart failure hospitalization in CHARM in patients stratified by ejection fraction and presence or absence of a HF hospitalization prior to enrollment.