Association of Sacubitril/Valsartan vs Valsartan With Blood Pressure Changes and Symptomatic Hypotension: the PARAGLIDE-HF Trial.

Autor: Fudim M; Duke Clinical Research Institute, Durham, NC, USA. Electronic address: marat.fudim@duke.edu., Cyr DD; Duke Clinical Research Institute, Durham, NC, USA., Ward JH; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA., Hernandez AF; Duke Clinical Research Institute, Durham, NC, USA., Lepage S; Department of Cardiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada., Morrow DA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Sharma K; Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Claggett BL; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Starling RC; Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA., Velazquez EJ; Department of Internal Medicine, Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, USA., Williamson KM; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA., Desai AS; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Zieroth S; Section of Cardiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada., Solomon SD; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Braunwald E; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Mentz RJ; Duke Clinical Research Institute, Durham, NC, USA.
Jazyk: angličtina
Zdroj: Journal of cardiac failure [J Card Fail] 2024 May 26. Date of Electronic Publication: 2024 May 26.
DOI: 10.1016/j.cardfail.2024.04.030
Abstrakt: Background: In PARAGLIDE-HF, in patients with ejection fraction (EF) > 40%, stabilized after worsening heart failure (WHF), sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared to valsartan alone, despite more symptomatic hypotension (SH). Concern about SH may be limiting the use of sacubitril/valsartan in appropriate patients.
Methods: We characterized patients by the occurrence of SH (investigator-reported) after randomization to either sacubitril/valsartan or valsartan. A key trial inclusion criterion was systolic blood pressure (SBP) ≥ 100 mmHg for the preceding 6 hours and no SH. We also compared outcomes based on baseline SBP stratified by the median blood pressure. The primary endpoint was time-averaged proportional change in NT-proBNP levels from baseline through weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: (1) cardiovascular death; (2) hospitalizations due to HF; (3) urgent HF visits; and (4) change in NT-proBNP levels.
Results: Among 466 randomized patients, 92 (19.7%) experienced SH (sacubitril/valsartan, n = 56 [24.0%]; valsartan, n = 36 [15.5%]; P = 0.020). The median time to the first SH event was similar between treatment arms (18 days vs 15 days, respectively; P = 0.42) as was the proportion of first SH events classified as serious by investigators. Patients who experienced SH with sacubitril/valsartan were more likely to be white (OR 1.87 [95% CI: 0.31, 11.15]), to have a lower baseline SBP (per 10 mmHg increase, OR 0.68 [95% CI: 0.55, 0.85]), or to have a left ventricular ejection fraction (LVEF) of > 60% (OR 2.21 [95% CI: 1.05, 4.65]). Time-averaged change in NT-proBNP levels did not differ between patients with baseline SBP ≥ 128 mmHg vs SBP < 128 mmHg (interaction, P = 0.43). The composite hierarchical outcome for sacubitril/valsartan in patients with baseline SBP ≥ 128 mmHg had a win ratio of 1.34 ([95% CI: 0.91, 1.99]; P = 0.096) vs SBP < 128 mmHg with a win ratio of 1.09 ([95%CI: 0.73, 1.66]; P = 0 .62; interaction P value = 0.42).
Conclusion: Among patients with LVEF > 40% stabilized after WHF, incident SH was more common with sacubitril/valsartan compared with valsartan. SH was associated with lower baseline SBP, being white, and having higher LVEF. Treatment benefits with sacubitril/valsartan may be more pronounced in patients with higher baseline SBP and lower LVEF (≤ 60%). (Funded by Novartis Pharmaceutical Corporation; ClinicalTrials.gov number, NCT03988634.).
Competing Interests: Disclosures MF was supported by the NIH and Doris Duke, received consulting fees from Abbott, Ajax, Alio Health, Alleviant, Artha, Audicor, AxonTherapies, Bayer, Bodyguide, Bodyport, Boston Scientific, Broadview, Cadence, Cardioflow, Cardionomics, Coridea, CVRx, Daxor, Deerfield Catalyst, Edwards LifeSciences, Echosens, EKO, Feldschuh Foundation, Fire1, FutureCardia, Galvani, Gradient, Hatteras, HemodynamiQ, Impulse Dynamics, Intershunt, Medtronic, Merck, NIMedical, NovoNordisk, NucleusRx, NXT Biomedical, Orchestra, Pharmacosmos, PreHealth, Presidio, Procyreon, ReCor, Rockley, SCPharma, Shifamed, Splendo, Summacor, SyMap, Verily, Vironix, Viscardia, and Zoll. DAM is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women's Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc., Janssen Research and Development, LLC, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Roche, Siemens Healthcare Diagnostics, Softcell Medical Limited, and Zora Biosciences and has received consulting fees from Abbott Laboratories, ARCA Biopharma, Inflammatix, Merck, Novartis, and Roche Diagnostics. KS serves as an advisory board member and/or consultant to AstraZeneca, Alleviant, Bayer, Boehringer-Ingelheim, Imbria, Novartis, NovoNordisk, RIVUS, and ViCardia. She receives grant funding from Amgen and American Heart Association. SDS has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, GSK, Ionis, Lilly, MyoKardia, NIH/NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, and Theracos, and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, and Akros. RCS serves on the steering committee for the PARAGLIDE trial, sponsored by Novartis. EJV reports grants from Novartis, Amgen, Phillips, and NHLBI/NIH. SDS has received research grants has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, NIH/NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, Valo. ASD has received research grants (to BWH) from Abbott, Alnylam, AstraZeneca, Bayer, Novartis and personal consulting fees from Abbott, Alnylam, AstraZeneca, Avidity Biopharma, Axon Therapeutics, Bayer, Biofourmis, Cytokinetics, GlaxoSmithKline, Medpace, Merck, New Amsterdam, Novartis, Parexel, Regeneron, River2Renal, Roche, Verily, Veristat. SZ received research grant support, served on advisory boards for or speaker engagements with Abbott, Akcea AstraZeneca, Amgen, Alnylam, Bayer, BMS, Boehringer Ingelheim, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Servier and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer. EB reports grant support to his institution from Novartis for the conduct of the PIONEER-HF trial (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP [N-terminal pro-B type natriuretic peptide] in Patients Stabilized From an Acute HF Episode), for serving on the executive committee of the PARADISE-MI (Prospective ARNI [angiotensin receptor neprilysin inhibitor] vs ACE [angiotensin-converting enzyme] Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) trial and the Steering Committee of the PARAGLIDE-HF trial, and for participation in an advisory board meeting. RJM receives research support and/or honoraria from Novartis, Abbott, AmericanRegent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novo Nordisk, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. JHW, SS and KMW are employees of Novartis. AFH reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Novartis, Somologic, Verily and consulting from Amgen, AstraZeneca, Bayer, Bristol-Myers Squib Boehringer Ingelheim, Boston Scientific, Cytokinetics, Merck, Novartis, and Novo Nordisk. All other authors have nothing to disclose.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: