Abstract
Aims: Patients surviving an acute myocardial infarction (AMI) are at risk of developing symptomatic heart failure (HF) or premature death. We hypothesized that sacubitril/valsartan, effective in the treatment of chronic HF, prevents development of HF and reduces cardiovascular death following high-risk AMI compared to a proven angiotensin-converting enzyme (ACE) inhibitor. This paper describes the study design and baseline characteristics of patients enrolled in the Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial. Methods and results: PARADISE-MI, a multinational (41 countries), double-blind, active-controlled trial, randomized patients within 0.5–7 days of presentation with index AMI to sacubitril/valsartan or ramipril. Transient pulmonary congestion and/or left ventricular ejection fraction (LVEF) ≤40% and at least one additional factor augmenting risk of HF or death (age ≥70 years, estimated glomerular filtration rate <60 mL/min/1.73 m2, diabetes, prior myocardial infarction, atrial fibrillation, LVEF <30%, Killip class ≥III, ST-elevation myocardial infarction without reperfusion) were required for inclusion. PARADISE-MI was event-driven targeting 708 primary endpoints (cardiovascular death, HF hospitalization or outpatient development of HF). Randomization of 5669 patients occurred 4.3 ± 1.8 days from presentation with index AMI. The mean age was 64 ± 12 years, 24% were women. The majority (76%) qualified with ST-segment elevation myocardial infarction; acute percutaneous coronary intervention was performed in 88% and thrombolysis in 6%. LVEF was 37 ± 9% and 58% were in Killip class ≥II. Conclusions: Baseline therapies in PARADISE-MI reflect advances in contemporary evidence-based care. With enrollment complete PARADISE-MI is poised to determine whether sacubitril/valsartan is more effective than a proven ACE inhibitor in preventing development of HF and cardiovascular death following AMI.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | European Journal of Heart Failure |
| Vol/bind | 23 |
| Udgave nummer | 6 |
| Sider (fra-til) | 1040-1048 |
| Antal sider | 9 |
| ISSN | 1388-9842 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:PARADISE‐MI was sponsored by Novartis.
Funding Information:
PARADISE-MI was sponsored by Novartis. Conflict of interest: K.S.J. is supported by the National Institutes of Health (Training Grant 5- T32 HL007604). B.C. has received consultancy fees from Amgen, Boehringer Ingelheim, Gilead, Novartis, AOBiome, and Corvia. M.A.P. has received research grant support (through Brigham and Women's Hospital) from Novartis; consulting fees from AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Corvidia, DalCor, GlaxoSmithKline, NHLBI CONNECTs (Master Protocol Committee), Novartis, Novo Nordisk, Peerbridge and Sanofi; and has equity in DalCor and Peerbridge. C.G. has received consultancy fees and/or research support from Novartis, AbbVie, Inc.
Funding Information:
: K.S.J. is supported by the National Institutes of Health (Training Grant 5‐ T32 HL007604). B.C. has received consultancy fees from Amgen, Boehringer Ingelheim, Gilead, Novartis, AOBiome, and Corvia. M.A.P. has received research grant support (through Brigham and Women's Hospital) from Novartis; consulting fees from AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Corvidia, DalCor, GlaxoSmithKline, NHLBI CONNECTs (Master Protocol Committee), Novartis, Novo Nordisk, Peerbridge and Sanofi; and has equity in DalCor and Peerbridge. C.G. has received consultancy fees and/or research support from Novartis, AbbVie, Inc., American Heart Association, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Boston Scientific Corporation, Bristol‐Myers Squibb, Celecor, Correvio, Daiichi Sankyo Co., Espero, Janssen Pharmaceuticals (Johnson & Johnson), Mayo Clinic, McGraw‐Hill Publishing, Medtronic, NC State University, NIH/NHLBI, Novo Nordisk, Pfizer Inc., Rho, Inc., Roche Diagnostics, Up to Date, WebMD/Medscape. L.K. has received a speaker's honorarium from Novartis, AstraZeneca, Novo and Boehringer. E.F.L. has received funding for research grants from Novartis. A.P.M. has received personal fees for participation in study committees sponsored by Novartis, Bayer and Fresenius. D.M. has received funding from Novartis and serves on the Scientific Advisory Board for MyoKardia, Bristol Myers Squibb. J.J.V.McM. has received payments from Abbott, Hikma, Ionis, Sun Pharmaceuticals, Servier, and his employer, Glasgow University, has received funding for his work on clinical trials, consulting and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, Dal‐Cor, GSK, KBP Biosciences, Novartis, Pfizer, and Theracos. J.L.R. has received consultancy fees from Novartis, AstraZeneca, Aventis, BMS/Myokardia, Abbott, Bayer. S.D.S. has received research grants (through Brigham and Women's Hospital) from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and has consulted for Abbott, Action Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer‐Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi‐Sankyo, Gilead, GSK, Ironwood, Lilly, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi‐Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent. P.G.S. received research grants from Amarin, Bayer, Sanofi, and Servier, and speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Bristol Myers Squibb, Idorsia, Myokardia, Novartis, NovoNordisk, PhaseBio, Pfizer, Regeneron, Sanofi, Servier. P.v.d.M. received consultancy fees and/or grants from Novartis, Corvidia, Servier, Vifor Pharma, AstraZeneca, Pfizer, Pharmacosmos and Ionis. M.W., K.C., W.G., Y.Z., M.L., J.G. and Y.W. are full‐time employees of Novartis. J.C.N. reports personal fees from Amgen, grants from AstraZeneca, Bristol Myers Squibb, CLS Behring, Dalcor, Janssen, NovoNordisk, Vifor, grants and personal fees from Bayer, Novartis, Sanofi, personal fees from Daiichi‐Sankyo, Servier. E.B. has received research grants (through Brigham and Women's Hospital) from AstraZeneca, Daiichi‐Sankyo, Merck, and Novartis; consultancies with Amgen, Boehringer Ingelheim/Lilly, Cardurion, MyoKardia, NovoNordisk, and Verve. All other authors have nothing to disclose. Conflict of interest
Publisher Copyright:
© 2021 European Society of Cardiology