Designing Future Clinical Trials in Heart Failure With Preserved Ejection Fraction: Lessons From TOPCAT

Ravi B. Patel; Sanjiv J. Shah; Gregg C. Fonarow; Javed Butler; Muthiah Vaduganathan

doi:10.1007/s11897-017-0336-x

Designing Future Clinical Trials in Heart Failure With Preserved Ejection Fraction: Lessons From TOPCAT

Ravi B. Patel, Sanjiv J. Shah, Gregg C. Fonarow, Javed Butler, Muthiah Vaduganathan^*

^*Corresponding author for this work

Medicine, Cardiology Division

Research output: Contribution to journal › Review article › peer-review

13 Scopus citations

Abstract

Purpose of Review: Spironolactone did not demonstrate benefit with respect to the primary composite endpoint in the global TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial in patients with chronic heart failure with preserved ejection fraction (HFpEF). We identify key lessons from the TOPCAT experience that can be applied to future HFpEF trials. Recent Findings: Subsequent analyses of TOPCAT have revealed marked regional heterogeneity in patient profiles, event rates, drug adherence, and treatment effects. Significant regional variation may impact the success of global HFpEF trials. Given potential benefits in the Americas subgroup in TOPCAT, mineralocorticoid receptor antagonists can be considered in appropriately selected patients with HFpEF to reduce risk of heart failure hospitalization. A planned registry-based trial should provide additional evidence regarding the role of spironolactone in HFpEF. Summary: The overall design, execution, and study oversight of TOPCAT have provided key insights into the conduct of future HFpEF trials.

Original language	English (US)
Pages (from-to)	217-222
Number of pages	6
Journal	Current heart failure reports
Volume	14
Issue number	4
DOIs	https://doi.org/10.1007/s11897-017-0336-x
State	Published - Aug 1 2017

Keywords

Clinical trials
Heart failure with preserved ejection fraction
International variation
Mineralocorticoid receptor antagonists
Spironolactone
Study design

ASJC Scopus subject areas

Emergency Medicine
Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1007/s11897-017-0336-x

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@article{af8c616e8a7c43cdb6171ab864b0a2a6,

title = "Designing Future Clinical Trials in Heart Failure With Preserved Ejection Fraction: Lessons From TOPCAT",

abstract = "Purpose of Review: Spironolactone did not demonstrate benefit with respect to the primary composite endpoint in the global TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial in patients with chronic heart failure with preserved ejection fraction (HFpEF). We identify key lessons from the TOPCAT experience that can be applied to future HFpEF trials. Recent Findings: Subsequent analyses of TOPCAT have revealed marked regional heterogeneity in patient profiles, event rates, drug adherence, and treatment effects. Significant regional variation may impact the success of global HFpEF trials. Given potential benefits in the Americas subgroup in TOPCAT, mineralocorticoid receptor antagonists can be considered in appropriately selected patients with HFpEF to reduce risk of heart failure hospitalization. A planned registry-based trial should provide additional evidence regarding the role of spironolactone in HFpEF. Summary: The overall design, execution, and study oversight of TOPCAT have provided key insights into the conduct of future HFpEF trials.",

keywords = "Clinical trials, Heart failure with preserved ejection fraction, International variation, Mineralocorticoid receptor antagonists, Spironolactone, Study design",

author = "Patel, {Ravi B.} and Shah, {Sanjiv J.} and Fonarow, {Gregg C.} and Javed Butler and Muthiah Vaduganathan",

note = "Funding Information: Javed Butler has received research support from the NIH and European Union, and has been a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis, Relypsa, ZS Pharma, Medtronic, Merck, and CVRx. Funding Information: Sanjiv J. Shah reports receiving research support from the National Institutes of Health (R01 HL107577, R01 HL127028), the American Heart Association (16SFRN28780016, 15CVGPSD27260148), Actelion, AstraZeneca, Corvia, and Novartis and serving as a consultant for Actelion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiora, Eisai, Gilead, Ironwood, Merck, MyoKardia, Novartis, Sanofi, and United Therapeutics. Funding Information: Gregg C. Fonarow reports significant consulting for Novartis and modest consulting for Amgen, Janssen, Novartis, Medtronic, and St. Jude Medical; Dr. Fonarow holds the Eliot Corday Chair of Cardiovascular Medicine at UCLA and is also supported by the Ahmanson Foundation (Los Angeles, CA). Publisher Copyright: {\textcopyright} 2017, Springer Science+Business Media, LLC.",

year = "2017",

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doi = "10.1007/s11897-017-0336-x",

language = "English (US)",

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journal = "Current Heart Failure Reports",

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T1 - Designing Future Clinical Trials in Heart Failure With Preserved Ejection Fraction

T2 - Lessons From TOPCAT

AU - Patel, Ravi B.

AU - Shah, Sanjiv J.

AU - Fonarow, Gregg C.

AU - Butler, Javed

AU - Vaduganathan, Muthiah

N1 - Funding Information: Javed Butler has received research support from the NIH and European Union, and has been a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis, Relypsa, ZS Pharma, Medtronic, Merck, and CVRx. Funding Information: Sanjiv J. Shah reports receiving research support from the National Institutes of Health (R01 HL107577, R01 HL127028), the American Heart Association (16SFRN28780016, 15CVGPSD27260148), Actelion, AstraZeneca, Corvia, and Novartis and serving as a consultant for Actelion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiora, Eisai, Gilead, Ironwood, Merck, MyoKardia, Novartis, Sanofi, and United Therapeutics. Funding Information: Gregg C. Fonarow reports significant consulting for Novartis and modest consulting for Amgen, Janssen, Novartis, Medtronic, and St. Jude Medical; Dr. Fonarow holds the Eliot Corday Chair of Cardiovascular Medicine at UCLA and is also supported by the Ahmanson Foundation (Los Angeles, CA). Publisher Copyright: © 2017, Springer Science+Business Media, LLC.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Purpose of Review: Spironolactone did not demonstrate benefit with respect to the primary composite endpoint in the global TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial in patients with chronic heart failure with preserved ejection fraction (HFpEF). We identify key lessons from the TOPCAT experience that can be applied to future HFpEF trials. Recent Findings: Subsequent analyses of TOPCAT have revealed marked regional heterogeneity in patient profiles, event rates, drug adherence, and treatment effects. Significant regional variation may impact the success of global HFpEF trials. Given potential benefits in the Americas subgroup in TOPCAT, mineralocorticoid receptor antagonists can be considered in appropriately selected patients with HFpEF to reduce risk of heart failure hospitalization. A planned registry-based trial should provide additional evidence regarding the role of spironolactone in HFpEF. Summary: The overall design, execution, and study oversight of TOPCAT have provided key insights into the conduct of future HFpEF trials.

AB - Purpose of Review: Spironolactone did not demonstrate benefit with respect to the primary composite endpoint in the global TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial in patients with chronic heart failure with preserved ejection fraction (HFpEF). We identify key lessons from the TOPCAT experience that can be applied to future HFpEF trials. Recent Findings: Subsequent analyses of TOPCAT have revealed marked regional heterogeneity in patient profiles, event rates, drug adherence, and treatment effects. Significant regional variation may impact the success of global HFpEF trials. Given potential benefits in the Americas subgroup in TOPCAT, mineralocorticoid receptor antagonists can be considered in appropriately selected patients with HFpEF to reduce risk of heart failure hospitalization. A planned registry-based trial should provide additional evidence regarding the role of spironolactone in HFpEF. Summary: The overall design, execution, and study oversight of TOPCAT have provided key insights into the conduct of future HFpEF trials.

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KW - Mineralocorticoid receptor antagonists

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Designing Future Clinical Trials in Heart Failure With Preserved Ejection Fraction: Lessons From TOPCAT

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