Author + information
- Received January 2, 2020
- Revision received January 30, 2020
- Accepted February 3, 2020
- Published online April 6, 2020.
- Senthil Selvaraj, MD, MAa@senthil_selv,
- Brian L. Claggett, PhDb,
- Michael Böhm, MDc,d,
- Stefan D. Anker, MDc,d,
- Muthiah Vaduganathan, MD, MPHb,
- Faiez Zannad, MDe,
- Burkert Pieske, MDc,
- Carolyn S.P. Lam, MB, BS, PhDf,
- Inder S. Anand, MDg,
- Victor C. Shi, MDh,
- Martin P. Lefkowitz, MDh,
- John J.V. McMurray, MDi and
- Scott D. Solomon, MDb,∗ (, )@scottdsolomon
- aDivision of Cardiology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- bDivision of Cardiology, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- cDepartment of Internal Medicine and Cardiology, German Center for Cardiovascular Research partner site Berlin, Berlin, Germany
- dKlinik für Innere Medizin III, Universität des Saarlandes, Homburg, Germany
- eINSERM Centre d'Investigation Clinic 1433 and Universite de Lorraine, Centre Hospitalier Regional et Universitaire, Nancy, France
- fNational Heart Center Singapore and Duke–National University of Singapore, Singapore
- gDepartment of Cardiovascular Medicine, University of Minnesota, Minneapolis, Minnesota
- hNovartis, East Hanover, New Jersey
- iBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
- ↵∗Address for correspondence:
Dr. Scott D. Solomon, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Background Guidelines recommend targeting systolic blood pressure (SBP) <130 mm Hg in heart failure with preserved ejection fraction (HFpEF) with limited data.
Objectives This study sought to determine the optimal achieved SBP and whether the treatment effects of sacubitril/valsartan on outcomes are related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan.
Methods Using 4,795 trial participants, this study related baseline and time-updated mean achieved SBP quartiles (<120, 120 to 129, 130 to 139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total heart failure hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 16-week visit, the study assessed the relationship between SBP change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and N-terminal pro−B-type natriuretic peptide (NT-proBNP). The study analyzed whether the BP-lowering effects of sacubitril/valsartan accounted for its treatment effects.
Results Average age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120 to 129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval: 4.4 to 6.0) compared with valsartan at 4 weeks, which was not modified by baseline SBP. However, sacubitril/valsartan reduced SBP more in women (6.3 mm Hg) than men (4.0 mm Hg) (interaction p = 0.005). Change in SBP was directly associated with change in NT-proBNP (p < 0.001) but not KCCQ-OSS (p = 0.40). The association between sacubitril/valsartan and the primary outcome was not modified by baseline SBP (interaction p = 0.50) and was similar when adjusting for time-updated SBP, regardless of sex.
Conclusions Baseline and mean achieved SBP of 120 to 129 mm Hg identified the lowest risk patients with HFpEF. Baseline SBP did not modify the treatment effect of sacubitril/valsartan, and the BP-lowering effects of sacubitril/valsartan did not account for its effects on outcomes, regardless of sex. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)
- blood pressure
- heart failure hospitalization
- heart failure with preserved ejection fraction
PARAGON-HF was funded by Novartis. Dr. Selvaraj is supported by the National Institutes of Health (Training Grant 5-T32HL007843-23). Dr. Claggett has received consultancy fees from Boehringer Ingelheim, Gilead, AOBiome, Amgen, Novartis, Myokardia, and Corvia. Dr. Böhm is supported by the Deutsche Forschungsgemeinschaft (DFG, TTR 219); and has received support from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Novartis, ReCor, Servier, and Vifor. Dr. Anker has received grants from Vifor International and Abbott Vascular; and has received personal fees from Bayer, Boehringer Ingelheim, Brahms GmbH, Impulse Dynamics, Novartis, Servier, St. Jude Medical, and Vifor International. Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541); and has served on the Advisory Boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Zannad has received fees for serving on a Steering Committee from Janssen, Bayer, Boston Scientific, CVRx, and Boehringer Ingelheim; has received consulting fees from Amgen, Vifor Pharma–Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, and Merck; and has received consulting fees and fees for serving on a Steering Committee from AstraZeneca and serving as founder of cardiorenal and CVCT. Dr. Pieske has received fees for serving on a Steering Committee, for serving on an Advisory Board, and lecture fees from Bayer HealthCare Pharmaceuticals and Merck Sharp & Dohme; has received lecture fees from AstraZeneca; has received fees for serving on an Advisory Board and lecture fees from Bristol-Myers Squibb; has received fees for serving on an Advisory Board from Daiichi-Sankyo; and has received lecture fees and honoraria from Medscape. Dr. Lam has received grant support and fees for serving on an Advisory Board from Boston Scientific and Roche Diagnostics; has received grant support, fees for serving on an Advisory Board, and fees for serving on Steering Committees from Bayer; has received grant support from Medtronic; has received grant support and fees for serving on a Steering Committee from Vifor Pharma; has received fees for serving on an Advisory Board and fees for serving on Steering Committees from AstraZeneca and Novartis; has received fees for serving on an Advisory Board from Amgen, Boehringer Ingelheim, and Abbott Diagnostics; has received consulting fees from Merck and Stealth BioTherapeutics; has received fees for serving on a Steering Committee from Janssen Research and Development; has received lecture fees and consulting fees from Menarini; has received fees for serving on a Scientific Committee from Corvia Medical; has been a consultant for Biofourmis, Darma, Applied Therapeutics, MyoKardia, Cytokinetics, WebMD Global LLC, Radcliffe Group Ltd., and Corpus; serves as co-founder and nonexecutive director of eKo.ai; and holds a pending patent (PCT/SG2016/050217) on a method regarding diagnosis and prognosis of chronic heart failure. Dr. Anand has received fees for serving on a Steering Committee from AstraZeneca, ARCA Biopharma, Amgen, and LivaNova; has received fees for serving as chair of a Data and Safety Monitoring Board from Boston Scientific; has received fees for serving on an End-Point Committee from Boehringer Ingelheim; and has received fees for serving on an Advisory Board from Zensun. Drs. Lefkowitz and Shi hold stock in Novartis. Dr. McMurray has served as an executive committee member and coprincipal investigator of ATMOSPHERE and coprincipal investigator of the PARADIGM-HF and PARAGON-HF trials and his employer, Glasgow University, has been paid by Novartis for his time spent in these roles; has received travel expenses from Novartis, AstraZeneca, Cardiorentis, Amgen, Theracos, Abbvie, GlaxoSmithKline, Vifor-Fresenius, and Kings College Hospital; has been a member of a Steering Committee and Endpoint Committee for Cardiorentis; has been a member of a Steering Committee for Amgen, Oxford University/Bayer, Abbvie, Dal-Cor, GlaxoSmithKline, Vifor-Fresenius, Kidney Research UK (KRUK); has been a member of the Data Safety Monitoring Board for Pfizer and Merck; and has been a member of an Executive Committee for Novartis. Dr. Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol-Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and has consulted for Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya.
- Received January 2, 2020.
- Revision received January 30, 2020.
- Accepted February 3, 2020.
- 2020 American College of Cardiology Foundation
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