Randomized Controlled Trial

. 2024 May 21;149(21):1627-1638.

doi: 10.1161/CIRCULATIONAHA.124.069217. Epub 2024 Apr 6.

Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial

Adrian F Hernandez¹, Jacob A Udell², W Schuyler Jones¹, Stefan D Anker³, Mark C Petrie⁴, Josephine Harrington¹, Michaela Mattheus⁵, Svenja Seide⁵, Isabella Zwiener⁵, Offer Amir⁶, M Cecilia Bahit⁷, Johann Bauersachs⁸, Antoni Bayes-Genis^{9

10}, Yundai Chen¹¹, Vijay K Chopra¹², Gemma A Figtree¹³, Junbo Ge¹⁴, Shaun G Goodman^{15

16}, Nina Gotcheva¹⁷, Shinya Goto¹⁸, Tomasz Gasior^{19

20}, Waheed Jamal¹⁹, James L Januzzi²¹, Myung Ho Jeong²², Yuri Lopatin²³, Renato D Lopes¹, Béla Merkely²⁴, Puja B Parikh²⁵, Alexander Parkhomenko²⁶, Piotr Ponikowski²⁷, Xavier Rossello²⁸, Morten Schou²⁹, Dragan Simic³⁰, Philippe Gabriel Steg³¹, Joanna Szachniewicz³², Peter van der Meer³³, Dragos Vinereanu³⁴, Shelley Zieroth³⁵, Martina Brueckmann^{19

36}, Mikhail Sumin¹⁹, Deepak L Bhatt³⁷, Javed Butler^{38

39}

Affiliations

¹ Duke University Department of Medicine, Division of Cardiology, and Duke Clinical Research Institute, Durham, NC (A.F.H., W.S.J., J.H., R.D.L.).
² Women's College Hospital and Peter Munk Cardiac Centre, Toronto General Hospital, University of Toronto, Canada (J.A.U.).
³ Department of Cardiology (CVK) of German Heart Center Charité, Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany (S.D.A.).
⁴ School of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, UK (M.C.P.).
⁵ Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany (M.M., S.S., I.Z.).
⁶ Heart Institute, Hadassah Medical Center, The Hebrew University of Jerusalem, Israel (O.A.).
⁷ INECO Neurociencias Oroño, Fundación INECO, Rosario, Santa Fe, Argentina (M.C.B.).
⁸ Department of Cardiology and Angiology, Hannover Medical School, Germany (J. Bauersachs).
⁹ Heart Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain (A.B.-G.).
¹⁰ Department of Medicine, Universitat Autònomoa de Barcelona, Spain (A.B.-G.).
¹¹ Department of Cardiology, the First Medical Center of Chinese PLA General Hospital, Beijing, China (Y.C.).
¹² Max Super Speciality Hospital, Saket, New Delhi, India (V.K.C.).
¹³ Faculty of Medicine and Health, University of Sydney, Australia (G.A.F.).
¹⁴ Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai, China (J.G.).
¹⁵ Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.).
¹⁶ Division of Cardiology, Department of Medicine, St Michael's Hospital, Unity Health Toronto and Peter Munk Cardiac Centre, University Health Network, University of Toronto, Canada (S.G.G.).
¹⁷ Department of Cardiology, MHAT "National Cardiology Hospital" EAD, Sofia, Bulgaria (N.G.).
¹⁸ Department of Medicine (Cardiology), Tokai University School of Medicine, Isehara, Japan (S.G.).
¹⁹ Boehringer Ingelheim International GmbH, Ingelheim, Germany (T.G., W.J., M.B., M. Sumin).
²⁰ Collegium Medicum, Faculty of Medicine, WSB University, Dabrowa Gornicza, Poland (T.G.).
²¹ Division of Cardiology, Harvard Medical School and Massachusetts General Hospital, Boston (J.L.J.).
²² Chonnam National University Hospital and Medical School, Gwangju, Republic of Korea (M.H.J.).
²³ Volgograd State Medical University, Russia (Y.L.).
²⁴ Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.).
²⁵ Division of Cardiovascular Medicine, Department of Medicine, State University of New York at Stony Brook (P.B.P.).
²⁶ The Ukrainian Institute of Cardiology na MD Strazhesko, AMS Ukraine, Kyiv (A.P.).
²⁷ Institute of Heart Diseases, Wroclaw Medical University, Poland (P.P.).
²⁸ Hospital Universitari Son Espases, Health Research Institute of the Balearic Islands, University of the Balearic Islands, Palma de Mallorca, Spain (X.R.).
²⁹ Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark (M. Schou).
³⁰ Department of Cardiovascular Diseases, University Clinical Center Belgrade, Serbia (D.S.).
³¹ Université Paris-Cité, FACT (French Alliance for Cardiovascular Trials), INSERM U-1148, AP-HP, Hôpital Bichat, Paris, France (P.G.S.).
³² Jan Mikulicz-Radecki University Clinical Hospital, Wroclaw, Poland (J.S.).
³³ Department of Cardiology, University of Groningen, University Medical Centre Groningen, the Netherlands (P.v.d.M.).
³⁴ University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital, Bucharest, Romania (D.V.).
³⁵ Section of Cardiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada (S.Z.).
³⁶ First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany (M.B.).
³⁷ Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY (D.L.B.).
³⁸ Baylor Scott and White Research Institute, Dallas, TX (J. Butler).
³⁹ Department of Medicine, University of Mississippi, Jackson (J. Butler).

PMID: 38581389
PMCID: PMC11115458
DOI: 10.1161/CIRCULATIONAHA.124.069217

Randomized Controlled Trial

Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial

Adrian F Hernandez et al. Circulation. 2024.

. 2024 May 21;149(21):1627-1638.

doi: 10.1161/CIRCULATIONAHA.124.069217. Epub 2024 Apr 6.

Authors

Affiliations

¹ Duke University Department of Medicine, Division of Cardiology, and Duke Clinical Research Institute, Durham, NC (A.F.H., W.S.J., J.H., R.D.L.).
² Women's College Hospital and Peter Munk Cardiac Centre, Toronto General Hospital, University of Toronto, Canada (J.A.U.).
³ Department of Cardiology (CVK) of German Heart Center Charité, Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany (S.D.A.).
⁴ School of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, UK (M.C.P.).
⁵ Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany (M.M., S.S., I.Z.).
⁶ Heart Institute, Hadassah Medical Center, The Hebrew University of Jerusalem, Israel (O.A.).
⁷ INECO Neurociencias Oroño, Fundación INECO, Rosario, Santa Fe, Argentina (M.C.B.).
⁸ Department of Cardiology and Angiology, Hannover Medical School, Germany (J. Bauersachs).
⁹ Heart Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain (A.B.-G.).
¹⁰ Department of Medicine, Universitat Autònomoa de Barcelona, Spain (A.B.-G.).
¹¹ Department of Cardiology, the First Medical Center of Chinese PLA General Hospital, Beijing, China (Y.C.).
¹² Max Super Speciality Hospital, Saket, New Delhi, India (V.K.C.).
¹³ Faculty of Medicine and Health, University of Sydney, Australia (G.A.F.).
¹⁴ Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai, China (J.G.).
¹⁵ Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.).
¹⁶ Division of Cardiology, Department of Medicine, St Michael's Hospital, Unity Health Toronto and Peter Munk Cardiac Centre, University Health Network, University of Toronto, Canada (S.G.G.).
¹⁷ Department of Cardiology, MHAT "National Cardiology Hospital" EAD, Sofia, Bulgaria (N.G.).
¹⁸ Department of Medicine (Cardiology), Tokai University School of Medicine, Isehara, Japan (S.G.).
¹⁹ Boehringer Ingelheim International GmbH, Ingelheim, Germany (T.G., W.J., M.B., M. Sumin).
²⁰ Collegium Medicum, Faculty of Medicine, WSB University, Dabrowa Gornicza, Poland (T.G.).
²¹ Division of Cardiology, Harvard Medical School and Massachusetts General Hospital, Boston (J.L.J.).
²² Chonnam National University Hospital and Medical School, Gwangju, Republic of Korea (M.H.J.).
²³ Volgograd State Medical University, Russia (Y.L.).
²⁴ Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.).
²⁵ Division of Cardiovascular Medicine, Department of Medicine, State University of New York at Stony Brook (P.B.P.).
²⁶ The Ukrainian Institute of Cardiology na MD Strazhesko, AMS Ukraine, Kyiv (A.P.).
²⁷ Institute of Heart Diseases, Wroclaw Medical University, Poland (P.P.).
²⁸ Hospital Universitari Son Espases, Health Research Institute of the Balearic Islands, University of the Balearic Islands, Palma de Mallorca, Spain (X.R.).
²⁹ Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark (M. Schou).
³⁰ Department of Cardiovascular Diseases, University Clinical Center Belgrade, Serbia (D.S.).
³¹ Université Paris-Cité, FACT (French Alliance for Cardiovascular Trials), INSERM U-1148, AP-HP, Hôpital Bichat, Paris, France (P.G.S.).
³² Jan Mikulicz-Radecki University Clinical Hospital, Wroclaw, Poland (J.S.).
³³ Department of Cardiology, University of Groningen, University Medical Centre Groningen, the Netherlands (P.v.d.M.).
³⁴ University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital, Bucharest, Romania (D.V.).
³⁵ Section of Cardiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada (S.Z.).
³⁶ First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany (M.B.).
³⁷ Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY (D.L.B.).
³⁸ Baylor Scott and White Research Institute, Dallas, TX (J. Butler).
³⁹ Department of Medicine, University of Mississippi, Jackson (J. Butler).

PMID: 38581389
PMCID: PMC11115458
DOI: 10.1161/CIRCULATIONAHA.124.069217

Abstract

Background: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown.

Methods: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes.

Results: Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05).

Conclusions: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674.

Keywords: heart failure; hospitalization; myocardial infarction.

PubMed Disclaimer

Conflict of interest statement

Disclosures Dr Hernandez has served as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Intellia, Intercept, MyoKardia, Novartis, Novo Nordisk, Prolaio, and TikkunLev; and has received research funding from American Regent, Amgen, Bayer, Boehringer Ingelheim, Lilly, Merck, Novartis, Novo Nordisk, and Verily. Dr Bhatt has served on advisory boards for ANGIOWave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; on the board of directors for American Heart Association New York City, ANGIOWave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); has served as a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; has served on data monitoring committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); has received honoraria from American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC accreditation oversight committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor-in-chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest editor; associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); is named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital, which was assigned to Lexicon (neither Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (editor, Braunwald’s Heart Disease); has served as site coinvestigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has served as trustee for American College of Cardiology; and performed unfunded research for FlowCo. Dr Butler has served as a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronic, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Goto reports serving as Associate Editor for Circulation and receipt of a steering committee fee from the Duke Clinical Research Institute for EMPACT-MI. Dr Lopes reports research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi-Aventis; funding for educational activities or lectures from Pfizer, Daiichi Sankyo, and Novo Nordisk; and funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. Dr Amir reports serving as National PI-Steering committee member for the study and participated in paid lectures and advisory board meetings and clinical trials in Dr Amir’s department at Boehringer Ingelheim. Dr Beyes-Genis has lectured or participated in advisory boards for Abbott, AstraZeneca, Bayer, Boehringer-Ingelheim, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, and Vifor. Dr Bahit reports modest honorarium from MSD, Pfizer, Bristol Myers Squibb, CSL Behring, Janssen, Boehringer Ingelheim, and Anthos Therapeutics. Dr Bauersachs received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, Norgine, Edwards, and Roche not related to this article; and research support for Dr Bauersachs’ department from Zoll, CVRx, Abiomed, Norgine, and Roche, not related to this article. Dr Schou reports lecture fees from Novartis, Astra Zeneca, Bohringer, and Novo Nordisk. Dr Steg reports research grants from Amarin and Sanofi; clinical trial participation for Amarin, Amgen, AstraZeneca, Idorsia, Janssen, Novartis, Novo-Nordisk, and Sanofi; consulting or speaking for Amarin, Amgen, and Novo-Nordisk; and serving as senior associate editor at Circulation. Dr Parikh reports serving as a consultant for Medtronic, Inc and receipt of an institutional research grant from Abbott and Edwards Lifesciences. Dr Januzzi reports participation as a trustee of the American College of Cardiology, board member of Imbria Pharmaceuticals, and director at Jana Care; has received research support from Abbott, Applied Therapeutics, Bayer, BBMS, HeartFlow Inc, Innolife, and Roche Diagnostics, and consulting income from Abbott, AstraZeneca, Bayer, Beckman, Boehringer-Ingelheim, Janssen, Medtronic, Novartis, Prevencio, Quidel/Ortho, Roche Diagnostics, and Vascular Dynamics; and participates in clinical end point committees or data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Medtronic, Pfizer, Roche Diagnostics, and Takeda. Dr Goodman reports research grant support (eg, steering committee or data and safety monitoring committee) or speaker or consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and salary support or honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and TIMI Study Group (Brigham Health). Dr van der Meer reports support from the European Research Council (ERC CoG 101045236, DISSECT-HF); the UMCG, which employs Dr van der Meer, received consultancy fees or grants from Novartis, Pharmacosmos, Vifor Pharma, Astra Zeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi Sankyo, Boehringer Ingelheim, and Ionis. Dr Petrie reports research funding from Boehringer Ingelheim, Roche, SQ Innovations, Astra Zeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; and consultancy or trial committee participation from Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, Astra Zeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences. Dr Parkhomenko reports research grants and personal fees from Bayer, Amgen, Astra Zeneca, Boehringer Ingelheim, BMS/Pfizer, and Daiichi-Sankyo. Dr Vinereanu reports research grants and consultancy fees from Boehringer Ingelheim and research grants from Bayer Healthcare, Novartis, and Servier Pharmaceuticals LLC. Dr Zieroth reports research grant support, served on advisory boards for, or had speaker engagements with AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Janssen, Medtronic, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Salubrisbio, 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; nonindustry participation includes Canadian Medical and Surgical KT Group, CCS, CHFS, Charite, EOCI, Liv, Medscape, Ology, PACE-CME, Radcliffe, Reach MD, and Translational Medicine Academy. Dr Jones reports research grants from Bayer, Boehringer Ingelheim, Merck, Novartis, PCORI, and the National Institutes of Health. Drs Seide, Mattheus, Zwiener, Sumin, Gasior, Jamal, and Brueckmann are employees of Boehringer Ingelheim.

Figures

**Figure 1.**
**Time to first adverse event of heart failure or all-cause death and total number of heart failure hospitalizations. A**, Time to first adverse event of heart failure or all-cause death. B, Total number of heart failure hospitalizations. HR indicates hazard ratio; and RR, rate ratio.

**Figure 2.**
**Major heart failure outcomes.** *Number of patients with events for time to first event end points and number of events for total number of events end points. †Number of patients with events per 100 patient-years for time to first event end points and adjusted number of events per 100 patient-years (on the basis of negative binomial regression) for total number of event end points. ‡Hazard ratio (95% CI), P value on the basis of Cox proportional hazards model for time to first event end points, event rate ratio (95% CI) on the basis of negative binomial regression for total number of events end points. HHF indicates hospitalization for heart failure.

**Figure 3.**
**Time-to-event analyses of hospitalization for heart failure by order of event according to the Wei-Lin-Weissfeld model.** HHF indicates hospitalization for heart failure.

**Figure 4.**
**Time to first heart failure hospitalization, according to prespecified subgroups.** *Median time from index myocardial infarction (MI) diagnosis to randomization: 5.0 days. ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; HR, hazard ratio; MRA, mineralocorticoid receptor antagonist; NC, not calculated; NSTEMI, non–ST-segment–elevation myocardial infarction; SBP, systolic blood pressure; STEMI, ST-segment–elevation myocardial infarction; and T2D, type 2 diabetes.

**Figure 5.**
**Total number of heart failure hospitalizations, according to prespecified subgroups.** *Median time from index myocardial infarction (MI) diagnosis to randomization: 5.0 days. ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; MRA, mineralocorticoid receptor antagonist; NC, not calculated; NSTEMI, non–ST-segment–elevation myocardial infarction; SBP, systolic blood pressure; STEMI, ST-segment–elevation myocardial infarction; and T2D, type 2 diabetes.

**Figure 6.**
**Cumulative incidence function for time to first use of heart failure therapies after discharge until 6 months. A**, Diuretics (excluding mineralocorticoid receptor antagonist). B, Angiotensin receptor-neprilysin inhibitor. C, Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or angiotensin receptor-neprilysin inhibitor. D, Mineralocorticoid receptor antagonist. HR indicates hazard ratio.

See this image and copyright information in PMC

References

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Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial

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Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial

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