Elsevier

American Heart Journal

Volume 162, Issue 5, November 2011, Pages 900-906
American Heart Journal

Clinical Investigation
Congestive Heart Failure
Days 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

https://doi.org/10.1016/j.ahj.2011.08.003Get rights and content

Background

Conventional composite outcomes in heart failure (HF) trials, for example, time to cardiovascular death or first HF hospitalization, have recognized limitations. We propose an alternative outcome, days alive and out of hospital (DAOH), which incorporates mortality and all hospitalizations into a single measure. A refinement, the patient journey, also uses functional status (New York Heart Association [NYHA] class) measured during follow-up. The CHARM program is used to illustrate the methodology.

Methods

CHARM randomized 7,599 patients with symptomatic HF to placebo or candesartan, with median follow-up of 38 months. We related DAOH and percent DAOH (ie, percentage of time spent alive and out of hospital) to treatment using linear regression adjusting for follow-up time.

Results

Mean increase in DAOH for patients on candesartan versus placebo was 24.1 days (95% CI 9.8-38.3 days, P < .001). The corresponding mean increase in percent DAOH was 2.0% (95% CI 0.8%-3.1%, P < .001). These findings were dominated by reduced mortality (23 days) but enhanced by reduced time in hospital (1 day). Percent time spent in hospital because of HF was reduced by 0.10% (95% CI 0.04%-0.14%, P < .001). The patient journey analysis showed that patients in the candesartan group spent more follow-up time in NYHA classes I and II and less in NYHA class IV.

Conclusions

Days alive and out of hospital, especially percent DAOH, provide a valuable tool for summarizing the overall absolute treatment effect on mortality and morbidity. In future HF trials, percent DAOH can provide a useful alternative perspective on the effects of treatment.

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.

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Robert O. Bonow, MD, served as guest editor for this article.

RCT reg no. NCT00634400.

Clinical Trial Registration: http://clinicaltrials.gov/ct2/show/NCT00634400.

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For the CHARM Investigators and Committees

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