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Review
. 2015 Apr 28;65(16):1668-1682.
doi: 10.1016/j.jacc.2015.03.043.

Patient selection in heart failure with preserved ejection fraction clinical trials

Jacob P Kelly  1 , Robert J Mentz  2 , Alexandre Mebazaa  3 , Adriaan A Voors  4 , Javed Butler  5 , Lothar Roessig  6 , Mona Fiuzat  2 , Faiez Zannad  7 , Bertram Pitt  8 , Christopher M O'Connor  2 , Carolyn S P Lam  9
Affiliations
Review

Patient selection in heart failure with preserved ejection fraction clinical trials

Jacob P Kelly et al. J Am Coll Cardiol. .

Abstract

Recent clinical trials in patients with heart failure with preserved ejection fraction (HFpEF) have provided important insights into participant selection strategies. Historically, HFpEF trials have included patients with relatively preserved left ventricular ejection fraction ranging from 40% to 55% and a clinical history of heart failure. Contemporary HFpEF trials have also incorporated inclusion criteria such as hospitalization for HFpEF, altered functional capacity, cardiac structural and functional abnormalities, and abnormalities in neurohormonal status (e.g., elevated natriuretic peptide levels). Careful analyses of the effect of these patient selection criteria on outcomes in prior trials provide valuable lessons for future trial design. We review recent and ongoing HFpEF clinical trials from a patient selection perspective and appraise trial patient selection methodologies in relation to outcomes. This review reflects discussions between clinicians, scientists, trialists, regulators, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum in Paris, France, on December 6, 2013.

Keywords: clinical protocols; methodology; natriuretic peptides; patient selection.

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Conflict of interest statement

Disclosures: All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1
Figure 1. Inclusion Criteria That Alter Event Rates in HFpEF Clinical Trials
Representative inclusion criteria used in past, present, and future clinical trials of patients with HFpEF. HF = heart failure; HFpEF = heart failure with preserved ejection fraction.
Figure 2
Figure 2. Strategies to enrich event rates in HFpEF Clinical Trials
The appropriate use of specific inclusion criteria and targeted thresholds will facilitate the reduction or enrichment of event rates in well-designed clinical trials of patients with HFpEF. EF = ejection fraction; HF = heart failure; NP = natriuretic peptide. ↑= higher; ↓ = lower.
Central Illustration
Central Illustration. Methodological Recommendations to Enhance Clinical Trial Success Through Increased Event Rates
Previous and ongoing clinical trial inclusion criteria and methodological considerations are presented with recommendations to highlight the complexity of clinical trial design with associated recommendations to enhance event rates and future clinical trial success. CPET = cardiopulmonary exercise testing; EF = ejection fraction; HF = heart failure; HFpEF = heart failure with preserved ejection fraction; NP= natriuretic peptide; NT-proBNP = N-terminal pro-B-type natriuretic peptide.
See this image and copyright information in PMC

References

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