Clinical InvestigationCongestive Heart FailureCauses of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: Results from efficacy of vasopressin antagonism in heart failure outcome study with tolvaptan (EVEREST) program
Section snippets
Study design and population
The design and results of the EVEREST program has been reported previously.14, 15, 16 The trial was an event-driven, randomized, double-blind, placebo-controlled study designed to evaluate both the short-term and long-term efficacy of tolvaptan (an oral vasopressin V2 receptor blocker) supplemented to standard HF therapy in patients hospitalized with worsened HF. This patient population was enrolled at 359 sites and 20 countries throughout North America, Europe, and South America between
Study population
Of the 4,133 patients randomized in the EVEREST trial observed for a median of 9.9 months, there were 5,239 rehospitalizations and 1,080 deaths. As previously reported, there were no differences in the primary end points between the tolvaptan and placebo groups, and the Kaplan-Meier estimated 1-year mortality rate was 25.5%, and the hospitalization rate was 57.6%.16
Mode of death
Most deaths were CV deaths (86.8% of all deaths). The leading mode of death was for HF (47.2%), followed by SCD (30.0%), non-CV
Discussion
To the best of our knowledge, this is the first study to systematically and prospectively analyze the cause of death and rehospitalization in a population of patients hospitalized for HF and on modern medical therapy. We demonstrated a high rate of both death and rehospitalization. In addition, we found that most patients died of progressive HF and approximately one quarter of sudden and unexpected death. Despite a clinical trial population with relatively few comorbidities, approximately one
Conclusion
Future registries for AHFS should adjudicate events to obtain a more accurate real-world causes of death and rehospitalization. Eventually, clinical trials should be designed to target specific modes of death and rehospitalization to reduce such events. Knowledge of the causes of these events may allow for early initiation of appropriate treatment strategies in the early postdischarge period after a hospitalization for worsened HF.
Disclosures
Dr O'Connor reports having received funding from the National Heart Lung and Blood Institute (NHLBI), Amgen, Astra, Bristol-Meyers Squibb, GlaxoSmithKline, Guidant, Medtronic, Merck, Nitrox LLC, Novartis, Otsuka, Pfizer, ArcaBioPharma, Sanofi-Sythelabo, and MedPace; Dr Miller Reports having received research grants from Otsuka and Pfizer and honoraria from Medtronic, Nitromed, Novartis, Pfizer, Sanofi, and Scios Inc; Dr Blair reports having been a consultant for SigmaTau; Dr Konstam reports the
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Clinicaltrials.gov Identifier: NCT00071331.