Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction

The TOPCAT Trial

Maja Cikes, Brian Claggett, Amil M. Shah, Akshay S. Desai, Eldrin F. Lewis, Sanjiv J. Shah, Inder S. Anand, Eileen O'Meara, Jean L. Rouleau, Nancy K Sweitzer, James C. Fang, Sanjeev Saksena, Bertram Pitt, Marc A. Pfeffer, Scott D. Solomon

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objectives: This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF. Background: AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes. Methods: A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Results: Seven hundred sixty patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p < 0.0001) and secondary outcomes. Conclusions: AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302)

Original languageEnglish (US)
JournalJACC: Heart Failure
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Atrial Fibrillation
Heart Failure
Spironolactone
Random Allocation
Mineralocorticoid Receptor Antagonists
Electrocardiography
Confidence Intervals
Therapeutics
Mortality
South America
North America
Heart Arrest

Keywords

  • atrial fibrillation
  • echocardiography
  • heart failure outcomes
  • heart failure with preserved ejection fraction
  • spironolactone

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cikes, M., Claggett, B., Shah, A. M., Desai, A. S., Lewis, E. F., Shah, S. J., ... Solomon, S. D. (Accepted/In press). Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial. JACC: Heart Failure. https://doi.org/10.1016/j.jchf.2018.05.005

Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction : The TOPCAT Trial. / Cikes, Maja; Claggett, Brian; Shah, Amil M.; Desai, Akshay S.; Lewis, Eldrin F.; Shah, Sanjiv J.; Anand, Inder S.; O'Meara, Eileen; Rouleau, Jean L.; Sweitzer, Nancy K; Fang, James C.; Saksena, Sanjeev; Pitt, Bertram; Pfeffer, Marc A.; Solomon, Scott D.

In: JACC: Heart Failure, 01.01.2018.

Research output: Contribution to journalArticle

Cikes, M, Claggett, B, Shah, AM, Desai, AS, Lewis, EF, Shah, SJ, Anand, IS, O'Meara, E, Rouleau, JL, Sweitzer, NK, Fang, JC, Saksena, S, Pitt, B, Pfeffer, MA & Solomon, SD 2018, 'Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial', JACC: Heart Failure. https://doi.org/10.1016/j.jchf.2018.05.005
Cikes, Maja ; Claggett, Brian ; Shah, Amil M. ; Desai, Akshay S. ; Lewis, Eldrin F. ; Shah, Sanjiv J. ; Anand, Inder S. ; O'Meara, Eileen ; Rouleau, Jean L. ; Sweitzer, Nancy K ; Fang, James C. ; Saksena, Sanjeev ; Pitt, Bertram ; Pfeffer, Marc A. ; Solomon, Scott D. / Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction : The TOPCAT Trial. In: JACC: Heart Failure. 2018.
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abstract = "Objectives: This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF. Background: AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes. Methods: A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Results: Seven hundred sixty patients (43{\%}) had a history of AF (18{\%}) or AF on ECG at enrollment (25{\%}). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95{\%} confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3{\%} of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95{\%} confidence interval: 1.59 to 3.40; p < 0.0001) and secondary outcomes. Conclusions: AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302)",
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author = "Maja Cikes and Brian Claggett and Shah, {Amil M.} and Desai, {Akshay S.} and Lewis, {Eldrin F.} and Shah, {Sanjiv J.} and Anand, {Inder S.} and Eileen O'Meara and Rouleau, {Jean L.} and Sweitzer, {Nancy K} and Fang, {James C.} and Sanjeev Saksena and Bertram Pitt and Pfeffer, {Marc A.} and Solomon, {Scott D.}",
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T2 - The TOPCAT Trial

AU - Cikes, Maja

AU - Claggett, Brian

AU - Shah, Amil M.

AU - Desai, Akshay S.

AU - Lewis, Eldrin F.

AU - Shah, Sanjiv J.

AU - Anand, Inder S.

AU - O'Meara, Eileen

AU - Rouleau, Jean L.

AU - Sweitzer, Nancy K

AU - Fang, James C.

AU - Saksena, Sanjeev

AU - Pitt, Bertram

AU - Pfeffer, Marc A.

AU - Solomon, Scott D.

PY - 2018/1/1

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N2 - Objectives: This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF. Background: AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes. Methods: A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Results: Seven hundred sixty patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p < 0.0001) and secondary outcomes. Conclusions: AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302)

AB - Objectives: This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF. Background: AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes. Methods: A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Results: Seven hundred sixty patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p < 0.0001) and secondary outcomes. Conclusions: AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302)

KW - atrial fibrillation

KW - echocardiography

KW - heart failure outcomes

KW - heart failure with preserved ejection fraction

KW - spironolactone

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