Abstract
Aims: Recent guidelines have advocated for stricter systolic blood pressure (SBP) control in heart failure with preserved ejection fraction (HFpEF), though data regarding the optimal SBP in HFpEF are sparse. Methods and results: We analysed participants from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study with available baseline and 8-week visit SBP data (n = 1645). We related baseline SBP to several efficacy and safety outcomes. To determine whether blood pressure lowering was responsible for the potential beneficial effects of spironolactone observed in the Americas, we assessed the randomized treatment adjusting for baseline and change in 8-week SBP. The average age was 71.7 ± 9.7 years, 50% were women, and 79% were White. Patients in the lowest baseline SBP quartile were less often female, more often White, had lower body mass index, lower baseline diastolic blood pressure and pulse pressure, and more often had atrial fibrillation. After multivariable adjustment, there was no relationship observed between baseline SBP quartiles and any outcome. Spironolactone reduced SBP by 4.4 ± 0.6 mmHg compared with placebo (and consistently across baseline SBP quartiles). There was minimal change in the treatment effect for all outcomes after adjusting for baseline SBP and 8-week change in SBP. Conclusion: No relationship was observed between baseline SBP quartiles and outcomes in TOPCAT. The anti-hypertensive effects of spironolactone did not account for the potential benefit in cardiovascular outcomes in the Americas.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 483-490 |
| Number of pages | 8 |
| Journal | European Journal of Heart Failure |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2018 |
Keywords
- Blood pressure
- Heart failure hospitalization
- Heart failure with preserved ejection fraction
- Spironolactone
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
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Systolic blood pressure and cardiovascular outcomes in heart failure with preserved ejection fraction : an analysis of the TOPCAT trial. / Selvaraj, Senthil; Claggett, Brian; Shah, Sanjiv J.; Anand, Inder; Rouleau, Jean L.; Desai, Akshay S.; Lewis, Eldrin F.; Pitt, Bertram; Sweitzer, Nancy K.; Pfeffer, Marc A.; Solomon, Scott D.
In: European Journal of Heart Failure, Vol. 20, No. 3, 03.2018, p. 483-490.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Systolic blood pressure and cardiovascular outcomes in heart failure with preserved ejection fraction
T2 - an analysis of the TOPCAT trial
AU - Selvaraj, Senthil
AU - Claggett, Brian
AU - Shah, Sanjiv J.
AU - Anand, Inder
AU - Rouleau, Jean L.
AU - Desai, Akshay S.
AU - Lewis, Eldrin F.
AU - Pitt, Bertram
AU - Sweitzer, Nancy K.
AU - Pfeffer, Marc A.
AU - Solomon, Scott D.
N1 - Funding Information: Sponsor: National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, USA (N01 HC45207). ClinicalTrials.gov identifier: NCT00094302 (http://www.clinicaltrials.gov/ct2/show/NCT00094302). Conflict of interest: J.L.R. is a consultant for Novartis, Bayer and AstraZeneca. M.A.P. has received consulting fees from Aas-trom, Abbott Vascular, Amgen, Cerenis, Concert, Daiichi Sankyo, Fibrogen, Genzyme, GlaxoSmithKline, Hamilton Health Sciences, Medtronic, Merck, Novo Nordisk, Roche, Salix, Sanderling, Sanofi-Aventis, Serono, Servier, and Teva, as well as research grants from New England Research Institute via subcontract from the National Institutes of Health, Amgen, Celladon, Novartis, and Sanofi-Aventis. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin–angiotensin system in selected survivors of myocardial infarction with Novartis Pharmaceuticals Funding Information: This work was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, contract HHSN268200425207C. The content of this article does not necessarily represent the views of the National Heart, Lung, and Blood Institute or of the Department of Health and Human Services. Sponsor: National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, USA (N01 HC45207). ClinicalTrials.gov identifier: NCT00094302 (http://www.clinicaltrials.gov/ct2/show/NCT00094302). Conflict of interest: J.L.R. is a consultant for Novartis, Bayer and AstraZeneca. M.A.P. has received consulting fees from Aastrom, Abbott Vascular, Amgen, Cerenis, Concert, Daiichi Sankyo, Fibrogen, Genzyme, GlaxoSmithKline, Hamilton Health Sciences, Medtronic, Merck, Novo Nordisk, Roche, Salix, Sanderling, Sanofi-Aventis, Serono, Servier, and Teva, as well as research grants from New England Research Institute via subcontract from the National Institutes of Health, Amgen, Celladon, Novartis, and Sanofi-Aventis. The Brigham and Women's Hospital has patents for the use of inhibitors of the renin?angiotensin system in selected survivors of myocardial infarction with Novartis Pharmaceuticals on which M.A.P. is a coinventor. M.A.P. share of the licensing agreement is irrevocably transferred to charity. A.S.D. has received consulting fees from Novartis, Boston Scientific, Reata, Cardiomems, 5 am Ventures, Intel Corp, Coverys, and Relypsa, as well as research grants from AtCor Medical to support the Vascular Stiffness Ancillary Study to the TOPCAT trial, for which he is listed as principal investigator. E.F.L. has received research grants from the National Heart, Lung, and Blood Institute, Novartis, and Sanofi-Aventis. S.J.S. has received research grants from the American Heart Association, National Institutes of Health, Actelion, AstraZeneca, Corvia, and Novartis, and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Eisai, Gilead, Ironwood, Merck, MyoKardia, Novartis, Pfizer, Sanofi, and United Therapeutics. N.K.S. has received research grants from the National Institutes of Health. B.P. received consulting fees from Amorcyte, AstraZeneca, Aurasense, Bayer, BG Medicine, Gambro, Johnson & Johnson, Mesoblast, Novartis, Pfizer, Relypsa, and Takeda; received research grant support from Forest Laboratories; and holds stock in Aurasense, Relypsa, BG Medicine, and Aurasense. B.P. also reports a pending patent related to site-specific delivery of eplerenone to the myocardium. S.D.S. received consulting fees from Novartis and Bayer and research grants from the National Heart, Lung, and Blood Institute. The other authors report no conflicts. Funding Information: The design of the TOPCAT study has been described in detail previously.10 Briefly, TOPCAT was a multi-centre, international, randomized, double blinded, placebo-controlled trial of spironolactone in adults with HFpEF recruited from over 270 clinical sites. The trial was funded by the National Heart, Lung, and Blood Institute as a contract with the Brigham and Women’s Hospital (Clinical Coordinating Center) and the New England Research Institute (Data Coordinating Center). Enrollment began in August 2006 and ended in January 2012, and the primary results of the trial were published in April 201411 (mean follow-up was 3.5 years). The primary aim of the TOPCAT study was to determine whether treatment with spironolactone, compared with placebo, could produce a clinically meaningful reduction in the composite outcome of cardiovascular mortality, aborted cardiac arrest, or HF hospitalization in adults with symptomatic HF and documented LV ejection fraction (LVEF) ≥45%. All study participants provided written informed consent. Funding Information: on which M.A.P. is a coinventor. M.A.P. share of the licensing agreement is irrevocably transferred to charity. A.S.D. has received consulting fees from Novartis, Boston Scientific, Reata, Car-diomems, 5 am Ventures, Intel Corp, Coverys, and Relypsa, as well as research grants from AtCor Medical to support the Vascular Stiffness Ancillary Study to the TOPCAT trial, for which he is listed as principal investigator. E.F.L. has received research grants from the National Heart, Lung, and Blood Institute, Novartis, and Sanofi-Aventis. S.J.S. has received research grants from the American Heart Association, National Institutes of Health, Acte-lion, AstraZeneca, Corvia, and Novartis, and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Car-diora, Eisai, Gilead, Ironwood, Merck, MyoKardia, Novartis, Pfizer, Sanofi, and United Therapeutics. N.K.S. has received research grants from the National Institutes of Health. B.P. received consulting fees from Amorcyte, AstraZeneca, Aurasense, Bayer, BG Medicine, Gambro, Johnson & Johnson, Mesoblast, Novartis, Pfizer, Relypsa, and Takeda; received research grant support from Forest Laboratories; and holds stock in Aurasense, Relypsa, BG Medicine, and Aurasense. B.P. also reports a pending patent related to site-specific delivery of eplerenone to the myocardium. S.D.S. received consulting fees from Novartis and Bayer and research grants from the National Heart, Lung, and Blood Institute. The other authors report no conflicts. Funding Information: This work was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, contract HHSN268200425207C. The content of this article does not necessarily represent the views of the National Heart, Lung, and Blood Institute or of the Department of Health and Human Services. Publisher Copyright: © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology
PY - 2018/3
Y1 - 2018/3
N2 - Aims: Recent guidelines have advocated for stricter systolic blood pressure (SBP) control in heart failure with preserved ejection fraction (HFpEF), though data regarding the optimal SBP in HFpEF are sparse. Methods and results: We analysed participants from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study with available baseline and 8-week visit SBP data (n = 1645). We related baseline SBP to several efficacy and safety outcomes. To determine whether blood pressure lowering was responsible for the potential beneficial effects of spironolactone observed in the Americas, we assessed the randomized treatment adjusting for baseline and change in 8-week SBP. The average age was 71.7 ± 9.7 years, 50% were women, and 79% were White. Patients in the lowest baseline SBP quartile were less often female, more often White, had lower body mass index, lower baseline diastolic blood pressure and pulse pressure, and more often had atrial fibrillation. After multivariable adjustment, there was no relationship observed between baseline SBP quartiles and any outcome. Spironolactone reduced SBP by 4.4 ± 0.6 mmHg compared with placebo (and consistently across baseline SBP quartiles). There was minimal change in the treatment effect for all outcomes after adjusting for baseline SBP and 8-week change in SBP. Conclusion: No relationship was observed between baseline SBP quartiles and outcomes in TOPCAT. The anti-hypertensive effects of spironolactone did not account for the potential benefit in cardiovascular outcomes in the Americas.
AB - Aims: Recent guidelines have advocated for stricter systolic blood pressure (SBP) control in heart failure with preserved ejection fraction (HFpEF), though data regarding the optimal SBP in HFpEF are sparse. Methods and results: We analysed participants from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study with available baseline and 8-week visit SBP data (n = 1645). We related baseline SBP to several efficacy and safety outcomes. To determine whether blood pressure lowering was responsible for the potential beneficial effects of spironolactone observed in the Americas, we assessed the randomized treatment adjusting for baseline and change in 8-week SBP. The average age was 71.7 ± 9.7 years, 50% were women, and 79% were White. Patients in the lowest baseline SBP quartile were less often female, more often White, had lower body mass index, lower baseline diastolic blood pressure and pulse pressure, and more often had atrial fibrillation. After multivariable adjustment, there was no relationship observed between baseline SBP quartiles and any outcome. Spironolactone reduced SBP by 4.4 ± 0.6 mmHg compared with placebo (and consistently across baseline SBP quartiles). There was minimal change in the treatment effect for all outcomes after adjusting for baseline SBP and 8-week change in SBP. Conclusion: No relationship was observed between baseline SBP quartiles and outcomes in TOPCAT. The anti-hypertensive effects of spironolactone did not account for the potential benefit in cardiovascular outcomes in the Americas.
KW - Blood pressure
KW - Heart failure hospitalization
KW - Heart failure with preserved ejection fraction
KW - Spironolactone
UR - http://www.scopus.com/inward/record.url?scp=85034233606&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034233606&partnerID=8YFLogxK
U2 - 10.1002/ejhf.1060
DO - 10.1002/ejhf.1060
M3 - Article
C2 - 29148144
AN - SCOPUS:85034233606
VL - 20
SP - 483
EP - 490
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
SN - 1388-9842
IS - 3
ER -