Clinical InvestigationCongestive Heart FailureDays alive and out of hospital and the patient journey in patients with heart failure: Insights from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program
Section snippets
Patients: the CHARM program
The design, baseline findings, and primary results of the CHARM program have been reported in detail.10, 11, 12, 13, 14 In summary, the CHARM program consisted of 3 independent but related trials performed concurrently in which 7,599 patients with NYHA class II to IV chronic HF were randomized to candesartan (target dose, 32 mg once daily) or matching placebo added to conventional background treatments. The CHARM program consisted of 3 substudies. Patients with an left ventricular ejection
Days alive and out of hospital
Figure 1 shows the distribution of the number of DAOH for all 7,599 patients in the CHARM program.
The distribution is skewed to the left: patients who die, especially if they die early, have fewer DAOH. The variation in DAOH at the right-hand end of the distribution is largely caused by patients' differing length of potential follow-up from randomization to study closure. Because the 3 component studies in CHARM differed in their patterns of recruitment over time, any analysis of the treatment
Discussion
Many major clinical trials in HF have as primary end point the composite of CV death or HF hospitalization, and CHARM is one such example.13 This approach has 3 problems: it gives equal weight to hospitalization and deaths, whereas the latter is clearly a more important event, it only takes into account each patient's first hospitalization and ignores subsequent ones and it does not take account of the severity (duration) of any hospitalization. In addition, the focus is on HF events and CV
Disclosures
Drs Pfeffer, Swedberg, Granger, McMurray, and Yusuf have received research funding from AstraZeneca. Drs Pocock, Cleland, McMurray, Granger, Swedberg, Pfeffer, and Östergren have consulted or received honorarium from AstraZeneca. Dr Michelson is an employee of AstraZeneca. Mr Ariti reports no conflict of interest.
Funding Sources: The CHARM program was funded by AstraZeneca.
References (15)
- et al.
Key issues in end point selection for heart failure trials: composite end points
J Card Fail
(2005) - et al.
A comparison of the effects of carvedilol and metoprolol on well-being, morbidity, and mortality (the “patient journey”) in patients with heart failure: a report from the Carvedilol Or Metoprolol European Trial (COMET)
J Am Coll Cardiol
(2006) - et al.
Unconventional end points in cardiovascular clinical trials: should we be moving away from morbidity and mortality?
J Card Fail
(2009) - et al.
Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial
Lancet
(2003) - et al.
Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial
Lancet
(2003) - et al.
Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme
Lancet
(2003) - et al.
Candesartan in heart failure–assessment of reduction in mortality and morbidity (CHARM): rationale and design. Charm-Programme Investigators
J Card Fail
(1999)
Cited by (140)
Emergency Surgery, Multimorbidity and Hospital-Free Days: A Retrospective Observational Study
2023, Journal of Surgical ResearchImpact of Moderate Aortic Stenosis in Patients With Heart Failure With Reduced Ejection Fraction
2023, Journal of the American College of CardiologyInstitution-free days after critical illness: A multicenter retrospective study
2023, Journal of Critical CareDays at home after transcatheter or surgical aortic valve replacement in high-risk patients
2023, American Heart Journal
Robert O. Bonow, MD, served as guest editor for this article.
RCT reg no. NCT00634400.
Clinical Trial Registration: http://clinicaltrials.gov/ct2/show/NCT00634400.
- j
For the CHARM Investigators and Committees