PMID- 32297449 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 2055-5822 (Electronic) IS - 2055-5822 (Linking) VI - 7 IP - 3 DP - 2020 Jun TI - Angiotensin receptor neprilysin inhibition versus individualized RAAS blockade: design and rationale of the PARALLAX trial. PG - 856-864 LID - 10.1002/ehf2.12694 [doi] AB - AIMS: Although the effect of the angiotensin receptor blocker neprilysin inhibitor (ARNI) sacubitril/valsartan on heart failure (HF) hospitalizations and cardiovascular death has been evaluated, its effects on functional capacity in patients with HF and ejection fraction (EF) >40% has yet to be determined. In addition, no prior studies have compared sacubitril/valsartan with angiotensin-converting enzyme inhibitor therapy. We sought to compare the effect of ARNI to background-medication-based individualized comparators (BMICs) on N-terminal pro-B-type natriuretic peptide (NT-proBNP), functional capacity [6 min walk distance (6MWD)], symptoms, and quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ)] in patients with HF and EF >40% in a randomized clinical trial. METHODS: PARALLAX is a prospective, randomized, controlled, double-blind multicentre clinical trial in patients with chronic symptomatic HF with EF >40%, New York Heart Association (NYHA) class II-IV symptoms, elevated natriuretic peptides, and evidence of structural heart disease. Eligible patients are randomized to sacubitril/valsartan vs. BMIC for cardiovascular and related co-morbidities. BMIC includes (i) enalapril, (ii) valsartan, and (iii) placebo depending on the type of medical therapy prior to enrolment. The primary endpoints are the change in plasma NT-proBNP concentration from baseline to 12 weeks and the change from baseline in 6MWD distance at 24 weeks. The secondary endpoints assess quality of life and symptom burden. CONCLUSIONS: PARALLAX will determine if sacubitril/valsartan compared with standard medical therapy for co-morbidities improves NT-proBNP levels, exercise capacity, quality of life, and symptom burden in HF patients with EF >40%. CI - (c) 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. FAU - Wachter, Rolf AU - Wachter R AUID- ORCID: 0000-0003-2231-2200 AD - Clinic and Policlinic for Cardiology, University Hospital Leipzig, Leipzig, Germany. AD - Clinic for Cardiology and Pneumology, University Medical Center Gottingen and DZHK (German Center for Cardiovascular Research), partner site Gottingen, Gottingen, Germany. FAU - Shah, Sanjiv J AU - Shah SJ AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. FAU - Cowie, Martin R AU - Cowie MR AD - Faculty of Medicine, National Heart & Lung Institute, Imperial College, London, UK. FAU - Szecsody, Peter AU - Szecsody P AD - Novartis, Basel, Switzerland. FAU - Shi, Victor AU - Shi V AD - Novartis, East Hanover EastHanover NJ, USA. FAU - Ibram, Ghionul AU - Ibram G AD - Novartis, East Hanover EastHanover NJ, USA. FAU - Zhao, Ziqiang AU - Zhao Z AD - Novartis, Shanghai, China. FAU - Gong, Jianjian AU - Gong J AD - Novartis, East Hanover EastHanover NJ, USA. FAU - Klebs, Sven AU - Klebs S AD - Novartis Pharma GmbH, Nuremberg, Germany. FAU - Pieske, Burkert AU - Pieske B AD - Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charite University Medicine Berlin, Berlin, Germany. AD - Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany. AD - DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany. AD - Clinical Research Unit Cardiology, Berlin Institute of Health, Berlin, Germany. LA - eng GR - R01 HL107577/HL/NHLBI NIH HHS/United States GR - R01 HL127028/HL/NHLBI NIH HHS/United States GR - R01 HL140731/HL/NHLBI NIH HHS/United States GR - R01 HL149423/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200415 PL - England TA - ESC Heart Fail JT - ESC heart failure JID - 101669191 RN - 0 (Angiotensins) RN - 0 (Receptors, Angiotensin) RN - EC 3.4.24.11 (Neprilysin) SB - IM MH - *Angiotensins MH - Humans MH - *Neprilysin MH - Prospective Studies MH - Quality of Life MH - Receptors, Angiotensin MH - Renin-Angiotensin System MH - Stroke Volume PMC - PMC7261527 OTO - NOTNLM OT - Functional capacity OT - Heart failure with mid-range ejection fraction OT - Heart failure with preserved ejection fraction OT - Neprilysin inhibition OT - Quality of life OT - Randomized controlled trial COIS- The PARALLAX trial is sponsored by Novartis. R.W. received grants from the Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF), Boehringer Ingelheim, German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and the European Union; personal fees and/or investigator fees from Bayer, Berlin Chemie, Boehringer Ingelheim, Medtronic, Novartis, Servier, Bristol-Myers Squibb, Pfizer, Sanofi and CVRx, Boston Scientific, Gilead, Johnson & Johnson. S.J.S. is supported by grants from the National Institutes of Health (NIH; R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423); the American Heart Association (AHA; #16SFRN28780016 and #15CVGPSD27260148); and Actelion, AstraZeneca, Corvia, and Novartis and has served as a consultant/advisory board/steering committee member for Abbott, Actelion, AstraZeneca, Amgen, Bayer, Boehringer-Ingelheim, Cardiora, Coridea, CVRx, Eisai, Ionis, Ironwood, Merck, MyoKardia, Novartis, Pfizer, Sanofi, Tenax, and United Therapeutics. B.P. is the Principal Investigator of PARALLAX and received personal and institutional honoraria from Novartis for steering committee, advisory board, and speaker activities. BP also received steering committee and/or speaker fees from Bayer Healthcare, Merck, Daiichi-Sankyo, Servier, BMS, and AstraZeneca. MRC received grants from Medtronic, Boston Scientific, Abbott, Bayer and ResMed during the conduct of the study and has served as a consultant/advisor/steering committee member for Novartis, Servier, Bayer, Boston Scientific, Abbott, ResMed, AstraZeneca, NovoNordisk, Neurotronik, and FIRE1 Foundry. EDAT- 2020/04/17 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/04/15 CRDT- 2020/04/17 06:00 PHST- 2020/01/08 00:00 [received] PHST- 2020/03/09 00:00 [revised] PHST- 2020/03/12 00:00 [accepted] PHST- 2020/04/17 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/04/17 06:00 [entrez] PHST- 2020/04/15 00:00 [pmc-release] AID - EHF212694 [pii] AID - 10.1002/ehf2.12694 [doi] PST - ppublish SO - ESC Heart Fail. 2020 Jun;7(3):856-864. doi: 10.1002/ehf2.12694. Epub 2020 Apr 15.