Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction.
| Autor: | Butt JH; British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark., Dewan P; British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom., Jhund PS; British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom., Anand IS; Department of Medicine, VA Medical Center, Minneapolis, Minnesota, USA; University of Minnesota Medical Center, University of Minnesota, Minneapolis, Minnesota, USA., Atar D; Department of Cardiology, Oslo University Hospital Ulleval, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Ge J; Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China., Desai AS; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA., Echeverria LE; Heart Failure Unit and Cardiac Transplant Program, Fundación Cardiovascular de Colombia, Floridablanca, Santander, Colombia., Køber L; Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark., Lam CSP; National Heart Centre Singapore and Duke-National University of Singapore, Singapore., Maggioni AP; Associazione Nazionale Medici Cardiologi Ospedalieri, Florence, Italy., Martinez F; Universidad Nacional of Córdoba, Córdoba, Argentina., Packer M; Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas, USA., Rouleau JL; Institut de Cardiologie de Montréal, Université de Montréal, Montréal, Québec, Canada., Sim D; Department of Cardiology, National Heart Centre Singapore, Singapore., Van Veldhuisen DJ; Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands., Vrtovec B; University Medical Centre, Ljubljana, Slovenia., Zannad F; Inserm CIC 1433 and Université de Lorraine, Centre Hospitalier Régional Universitaire, Nancy, France., Zile MR; Medical University of South Carolina, Charleston, South Carolina, USA; Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina, USA., Gong J; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Lefkowitz MP; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Rizkala AR; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Solomon SD; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA., McMurray JJV; British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. Electronic address: john.mcmurray@glasgow.ac.uk. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of the American College of Cardiology [J Am Coll Cardiol] 2022 Sep 20; Vol. 80 (12), pp. 1130-1143. Date of Electronic Publication: 2022 Aug 29. |
| DOI: | 10.1016/j.jacc.2022.06.037 |
| Abstrakt: | Background: Frailty is an increasingly common problem, and frail patients are less likely to receive new pharmacologic therapies because the risk-benefit profile is perceived to be less favorable than in nonfrail patients. Objectives: This study investigated the efficacy of sacubitril/valsartan according to frailty status in 4,796 patients with heart failure with preserved ejection fraction randomized in the PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial. Methods: Frailty was measured by using the Rockwood cumulative deficit approach. The primary endpoint was total heart failure hospitalizations or cardiovascular death. Results: A frailty index (FI) was calculable in 4,795 patients. In total, 45.2% had class 1 frailty (FI ≤0.210, not frail), 43.5% had class 2 frailty (FI 0.211-0.310, more frail), and 11.4% had class 3 frailty (FI ≥0.311, most frail). There was a graded relationship between FI class and the primary endpoint, with a significantly higher risk associated with greater frailty (class 1: reference; class 2 rate ratio: 2.19 [95% CI: 1.85-2.60]; class 3 rate ratio: 3.29 [95% CI: 2.65-4.09]). The effect of sacubitril/valsartan vs valsartan on the primary endpoint from lowest to highest FI class (as a rate ratio) was: 0.98 [95% CI: 0.76-1.27], 0.92 [95% CI: 0.76-1.12], and 0.69 [95% CI: 0.51-0.95]), respectively (P Conclusions: Frailty was common in heart failure with preserved ejection fraction and associated with worse outcomes. Compared with valsartan, sacubitril/valsartan seemed to show a greater reduction in the primary endpoint with increasing frailty, although this was not significant when FI was examined as a categorical variable. (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711). Competing Interests: Funding Support and Author Disclosures The PARAGON-HF trial was funded by Novartis. Dr McMurray is supported by British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217. Dr Butt has received advisory board honoraria from Bayer, outside the submitted work. Dr Jhund has received consulting fees from Novo Nordisk AS, Novartis, AstraZeneca, and Boehringer Ingelheim. Dr Anand has received consulting fees from Amgen, ARCA Biopharma, AstraZeneca, Boston Scientific Corporation, Boehringer Ingelheim, LivaNova, Novartis, and Zensun. Dr. Atar has received honoraria from Actelion, AstraZeneca, Bayer-Healthcare, Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, Merck, and Novartis. Dr Desai has received grants and personal fees from AstraZeneca during the conduct of the study; has received personal fees from Abbott, Biofourmis, Boston Scientific, Boehringer Ingelheim, Corvidia, DalCor Pharma, Relypsa, Regeneron, and Merck; has received grants and personal fees from Alnylam and Novartis; and has received personal fees from Amgen, outside the submitted work. Dr Køber has received compensation from Novartis, Novo Nordisk, and AstraZeneca for consulting. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from AstraZeneca, Bayer, Boston Scientific, and Roche Diagnostics; has served as a consultant or on the advisory board/steering committee/executive committee for Actelion, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, Us2.ai, Janssen Research & Development LLC, Medscape, Merck, Novartis, Novo Nordisk, Radcliffe Group Ltd, Roche Diagnostics, Sanofi, and WebMD Global LLC; and serves as the cofounder and non-executive director of Us2.ai. Dr Maggioni has received fees for serving on a study committee from Bayer and Fresenius. Dr. Martinez has received personal fees from Novartis. Dr Packer has received consulting fees from AbbVie, Akcea, Actavis, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Daiichi-Sankyo, Gilead, Johnson & Johnson, Novo Nordisk, Pfizer, Relypsa, Sanofi, Synthetic Biologics, and Theravance. Dr Rouleau has received grants and consulting fees from Novartis; and has received consulting fees from Abbott, AstraZeneca, MyoKardia, and Sanofi. Dr Veldhuisen has received fees for serving on a steering committee and travel support from ARCA biopharma and Corvia Medical. Dr Zannad has received personal fees from Novartis, Janssen, Bayer, Boston Scientific, Amgen, CVRx, Boehringer Ingelheim, Cardiorenal, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, and CardioVascular Clinical Trialists (CVCT). Dr Zile has received research funding from Novartis; and has been a consultant for Novartis, Abbott, Boston Scientific, CVRx, EBR, Endotronics, Ironwood, Merck, Medtronic, and Myokardia V Wave. Dr Gong is an employee of Novartis. Dr Lefkowitz is an employee of Novartis. Dr Rizkala is an employee of and owns stock in Novartis. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellPro-Thera, Moderna, American Regent, and Sarepta. Dr McMurray has received payments through Glasgow University from work on clinical trials, consulting and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Cytokinetics, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; has received personal lecture fees from the Corpus, Abbott, Hikma, Sun Pharmaceuticals, Medscape/Heart.Org, Radcliffe Cardiology, Servier Director, and Global Clinical Trial Partners (GCTP). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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