Elsevier

American Heart Journal

Volume 163, Issue 6, June 2012, Pages 946-953.e1
American Heart Journal

Trial Design
Design and rationale of a retrospective clinical effectiveness study of aldosterone antagonist therapy in patients with heart failure

https://doi.org/10.1016/j.ahj.2012.03.007Get rights and content

Background

Despite demonstrated efficacy in randomized trials, aldosterone antagonist therapy is not used in many eligible patients with heart failure. Questions remain about its clinical effectiveness and safety for patients who are underrepresented in randomized trials and those at risk for hyperkalemia.

Methods

The proposed study will evaluate the effectiveness of aldosterone antagonist therapy in eligible Medicare beneficiaries ≥65 years old hospitalized for heart failure between 2005 and 2008. Data are from the GWTG-HF registry linked with Medicare inpatient and prescription drug event files. We will use inverse probability-weighted estimators to assess differences in mortality, cardiovascular readmission, and readmission for hyperkalemia between patients who receive or do not receive aldosterone antagonist therapy.

Results

The initial data set included 33,652 patients; 5,463 (16.2%) met all inclusion criteria. Compared with patients who did not meet the inclusion criteria, patients in the final cohort were more likely to be younger (77.3 vs 80.3 years) and male (63.8% vs 41.3%) and to have ischemic heart failure (74.2% vs 59.5%) (all P < .001). Mortality rates were 24.7% at 1 year and 50.7% at 3 years; cardiovascular readmission rates were 50.1% at 1 year and 65.2% at 3 years.

Conclusions

The proposed study will evaluate the clinical effectiveness of aldosterone antagonist therapy in Medicare beneficiaries hospitalized for heart failure with reduced ejection fraction, an underrepresented population in clinical trials. By addressing this evidence gap, the study has the potential to inform clinical decision making and improve patient outcomes.

Section snippets

Methods

The proposed study is a retrospective cohort study comparing outcomes of eligible Medicare beneficiaries who receive aldosterone antagonist therapy with outcomes of eligible beneficiaries who do not receive this therapy, overall and by clinically relevant subgroups. The null hypothesis is that receipt of aldosterone antagonist therapy at discharge has no effect on mortality and readmission rates at 1 and 3 years among Medicare beneficiaries aged ≥65 years who were hospitalized for heart

Results

Figure 1 shows the derivation of the study cohort. The initial linked data set included 33,652 patients, from which we excluded 8,899 patients who were not discharged home and 4,192 patients who did not have a documented history of heart failure before the index hospitalization. The restricted data set included 20,656 patients, from which we further excluded 14,722 patients who were not eligible for aldosterone antagonist therapy. After all exclusions, the study cohort included 5,934 patients

Discussion

In establishing priorities for comparative effectiveness research, the Institute of Medicine described the breadth of study designs, including “systematic reviews, database research, observational studies, and randomized trials,” that could be used to assess real-world outcomes.6 The need for openness and transparency in the registration and reporting of clinical trials is widely recognized, yet similar expectations have not been established for the range of nonrandomized study designs used

Disclosures

This study was funded under contract number HHSA29020050032I (Duke University DEcIDE Center) from the Agency for Healthcare Research and Quality, US Department of Health and Human Services, as part of the Developing Evidence to Inform Decisions About Effectiveness (DEcIDE) program. The GWTG-HF program is provided by the American Heart Association and is currently supported by an unrestricted educational grant from Medtronic, Inc. GWTG-HF has been supported previously by GlaxoSmithKline,

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    Philip F. Binkley, MD, MPH served as guest editor for this article.

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