PMID- 34861154 OWN - NLM STAT- MEDLINE DCOM- 20220421 LR - 20220421 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 10 IP - 1 DP - 2022 Jan TI - Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial. PG - 35-45 LID - S2213-8587(21)00292-8 [pii] LID - 10.1016/S2213-8587(21)00292-8 [doi] AB - BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as beta blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66.8 years [SD 11.0], 893 [23.9%] women; 1863 [49.9%] in the empagliflozin group, 1867 [50.1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0.75 [95% CI 0.65-0.86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0.85 [0.69-1.06]) and for doses of 50% or more of the target dose (HR 0.67 [0.52-0.88]; p(interaction)=0.18). A similar result was seen for beta blockers at doses of less than 50% of the target dose (HR 0.66 [0.54-0.80]) and for doses of 50% or more of the target dose (HR 0.81 [0.66-1.00]; p(interaction)=0.15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus beta blocker plus MRA (given combination HR 0.73 [0.61-0.88]; not given combination HR 0.76 [0.62-0.94]; p(interaction)=0.77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Toronto, ON, Canada. Electronic address: subodh.verma@unityhealth.to. FAU - Dhingra, Nitish K AU - Dhingra NK AD - Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Toronto, ON, Canada. FAU - Butler, Javed AU - Butler J AD - Department of Medicine, University of Mississippi School of Medicine, Jackson, MS, USA. FAU - Anker, Stefan D AU - Anker SD AD - Department of Cardiology and Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research Partner Site Berlin, Charite Universitatsmedizin, Berlin, Germany. FAU - Ferreira, Joao Pedro AU - Ferreira JP AD - Centre d'Investigations Cliniques Plurithematique 1433, Universite de Lorraine, Institut National de la Sante et de la Recherche Medicale 1116, Centre Hospitalier Regional Universitaire de Nancy, French Clinical Research Infrastructure Network, Investigation Network Initiative- Cardiovascular and Renal Clinical Trialists, Nancy, France; Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. FAU - Filippatos, Gerasimos AU - Filippatos G AD - National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon, Athens, Greece. FAU - Januzzi, James L AU - Januzzi JL AD - Division of Cardiology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA. FAU - Lam, Carolyn S P AU - Lam CSP AD - National Heart Centre Singapore, Duke- National University of Singapore Medical School, Singapore. FAU - Sattar, Naveed AU - Sattar N AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. FAU - Peil, Barbara AU - Peil B AD - Boehringer Ingelheim Pharma, Ingelheim, Germany. FAU - Nordaby, Matias AU - Nordaby M AD - Boehringer Ingelheim International, Ingelheim, Germany. FAU - Brueckmann, Martina AU - Brueckmann M AD - Boehringer Ingelheim International, Ingelheim, Germany; Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. FAU - Pocock, Stuart J AU - Pocock SJ AD - Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK. FAU - Zannad, Faiez AU - Zannad F AD - Centre d'Investigations Cliniques Plurithematique 1433, Universite de Lorraine, Institut National de la Sante et de la Recherche Medicale 1116, Centre Hospitalier Regional Universitaire de Nancy, French Clinical Research Infrastructure Network, Investigation Network Initiative- Cardiovascular and Renal Clinical Trialists, Nancy, France. FAU - Packer, Milton AU - Packer M AD - Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA; Imperial College London, London, UK. CN - EMPEROR-Reduced trial committees and investigators LA - eng SI - ClinicalTrials.gov/NCT03057977 PT - Comment PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211130 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Adrenergic beta-Antagonists) RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - HDC1R2M35U (empagliflozin) SB - IM CON - Lancet Diabetes Endocrinol. 2022 Jan;10(1):3-5. PMID: 34861151 MH - Adrenergic beta-Antagonists/pharmacology/therapeutic use MH - Aged MH - Angiotensin Receptor Antagonists/therapeutic use MH - Angiotensin-Converting Enzyme Inhibitors/therapeutic use MH - Benzhydryl Compounds MH - Double-Blind Method MH - Female MH - Glucosides MH - *Heart Failure/drug therapy MH - Humans MH - *Hypotension/drug therapy MH - Male MH - Stroke Volume/drug effects COIS- Declaration of interests SV holds a tier 1 Canada Research Chair in cardiovascular surgery; and reports receiving research grants and honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, PhaseBio, and Pfizer; and receiving honoraria from Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group. He is a member of the scientific excellence committee of the EMPEROR-Reduced trial and served as a national lead investigator of the DAPA-HF and EMPEROR-Reduced trials. He is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organisation. JB reports consulting fees from Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave, and Vifor. SDA has received grants from Vifor; personal fees from Vifor, Bayer, Boehringer Ingelheim, Novartis, Servier, Impulse Dynamics, Cardiac Dimensions, and Thermo Fisher Scientific; and grants and personal fees from Abbott Vascular. JPF reports consulting fees from Boehringer Ingelheim. GF reports honoraria for lectures for Medtronic, Vifor, Servier, Novartis, Bayer, Amgen, and Boehringer Ingelheim, and committee member contributions in trials sponsored by Boehringer Ingelheim. JLJ reports grant support, consulting income, and participation in clinical endpoint committees and data safety monitoring boards from Janssen; participation in clinical endpoint committees and data safety monitoring boards from Boehringer Ingelheim; grant support from Novartis, Innolife, Applied Therapeutics, and Siemens Diagnostics; and consultancy fees from Novartis, Roche Diagnostics, and Abbott Diagnostics. CSPL reports research grants from Bayer, Boston Scientific, Roche Diagnostic, Medtronic, Vifor Pharma, and AstraZeneca; consulting fees from Merck, Bayer, Boston Scientific, Roche Diagnostic, Vifor Pharma, AstraZeneca, Novartis, Amgen, Janssen Research and Development, Menarini, Boehringer Ingelheim, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, Novo Nordisk, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, Cytokinetics, WebMD Global, Radcliffe Group, and Corpus; and serves as co-founder and non-executive director of eKo.ai. NS reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novo Nordisk, Pfizer, and Sanofi; and grant income from Boehringer Ingelheim. BP, MN, and MB are employees of Boehringer Ingelheim. SJP reports personal fees from Boehringer Ingelheim. FZ reports personal fees from Boehringer Ingelheim, Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer, and Cellprothera; and other support from cardiovascular clinical trialists and Cardiorenal. MP reports personal fees from AbbVie, Actavis, Amgen, Amarin, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Casana, CSL Behring, Cytokinetics, Johnson & Johnson, Lilly, Moderna, Novartis, ParatusRx, Pfizer, Relypsa, Salamandra, Synthetic Biologics, and Theravance. NKD declares no competing interests. FIR - Packer, M IR - Packer M FIR - Anker, S IR - Anker S FIR - Butler, J IR - Butler J FIR - Filippatos, G IR - Filippatos G FIR - Pocock, S IR - Pocock S FIR - Zannad, F IR - Zannad F FIR - Ferreira, J P IR - Ferreira JP FIR - Brueckmann, M IR - Brueckmann M FIR - George, J IR - George J FIR - Jamal, W IR - Jamal W FIR - Welty, F K IR - Welty FK FIR - Palmer, M IR - Palmer M FIR - Clayton, T IR - Clayton T FIR - Parhofer, K G IR - Parhofer KG FIR - Pedersen, T R IR - Pedersen TR FIR - Greenberg, B IR - Greenberg B FIR - Konstam, M A IR - Konstam MA FIR - Lees, K R IR - Lees KR FIR - Carson, P IR - Carson P FIR - Doehner, W IR - Doehner W FIR - Miller, A IR - Miller A FIR - Haas, M IR - Haas M FIR - Pehrson, S IR - Pehrson S FIR - Komajda, M IR - Komajda M FIR - Anand, I IR - Anand I FIR - Teerlink, J IR - Teerlink J FIR - Rabinstein, A IR - Rabinstein A FIR - Steiner, T IR - Steiner T FIR - Kamel, H IR - Kamel H FIR - Tsivgoulis, G IR - Tsivgoulis G FIR - Lewis, J IR - Lewis J FIR - Freston, J IR - Freston J FIR - Kaplowitz, N IR - Kaplowitz N FIR - Mann, J IR - Mann J FIR - Petrie, J IR - Petrie J FIR - Perrone, S IR - Perrone S FIR - Nicholls, S IR - Nicholls S FIR - Janssens, S IR - Janssens S FIR - Bocchi, E IR - Bocchi E FIR - Giannetti, N IR - Giannetti N FIR - Verma, S IR - Verma S FIR - Zhang, J IR - Zhang J FIR - Spinar, J IR - Spinar J FIR - Seronde, M-F IR - Seronde MF FIR - Boehm, M IR - Boehm M FIR - Merkely, B IR - Merkely B FIR - Chopra, V IR - Chopra V FIR - Senni, M IR - Senni M FIR - Taddi, S IR - Taddi S FIR - Tsutsui, H IR - Tsutsui H FIR - Choi, D-J IR - Choi DJ FIR - Chuquiure, E IR - Chuquiure E FIR - La Rocca, Hpb IR - La Rocca H FIR - Ponikowski, P IR - Ponikowski P FIR - Juanatey, Jrg IR - Juanatey J FIR - Squire, I IR - Squire I FIR - Januzzi, J IR - Januzzi J FIR - Pina, I IR - Pina I FIR - Bernstein, R IR - Bernstein R FIR - Cheung, A IR - Cheung A FIR - Green, J IR - Green J FIR - Januzzi, J IR - Januzzi J FIR - Kaul, S IR - Kaul S FIR - Lam, C IR - Lam C FIR - Lip, G IR - Lip G FIR - Marx, N IR - Marx N FIR - McCullough, P IR - McCullough P FIR - Mehta, C IR - Mehta C FIR - Ponikowski, P IR - Ponikowski P FIR - Rosenstock, J IR - Rosenstock J FIR - Sattar, N IR - Sattar N FIR - Scirica, B IR - Scirica B FIR - Shah, S IR - Shah S FIR - Tsutsui, H IR - Tsutsui H FIR - Verma, S IR - Verma S FIR - Wanner, C IR - Wanner C FIR - Aizenberg, D IR - Aizenberg D FIR - Cartasegna, L IR - Cartasegna L FIR - Colombo Berra, F IR - Colombo Berra F FIR - Colombo, H IR - Colombo H FIR - Fernandez Moutin, M IR - Fernandez Moutin M FIR - Glenny, J IR - Glenny J FIR - Alvarez Lorio, C IR - Alvarez Lorio C FIR - Anauch, D IR - Anauch D FIR - Campos, R IR - Campos R FIR - Facta, A IR - Facta A FIR - Fernandez, A IR - Fernandez A FIR - Ahuad Guerrero, R IR - Ahuad Guerrero R FIR - Lobo Marquez, L IR - Lobo Marquez L FIR - Leon de la Fuente, R A IR - Leon de la Fuente RA FIR - Mansilla, M IR - Mansilla M FIR - Hominal, M IR - Hominal M FIR - Hasbani, E IR - Hasbani E FIR - Najenson, M IR - Najenson M FIR - Moises Azize, G IR - Moises Azize G FIR - Luquez, H IR - Luquez H FIR - Guzman, L IR - Guzman L FIR - Sessa, H IR - Sessa H FIR - Amuchastegui, M IR - Amuchastegui M FIR - Salomone, O IR - Salomone O FIR - Perna, E IR - Perna E FIR - Piskorz, D IR - Piskorz D FIR - Sicer, M IR - Sicer M FIR - Perez de Arenaza, D IR - Perez de Arenaza D FIR - Zaidman, C IR - Zaidman C FIR - Nani, S IR - Nani S FIR - Poy, C IR - Poy C FIR - Resk, J IR - Resk J FIR - Villarreal, R IR - Villarreal R FIR - Majul, C IR - Majul C FIR - Smith Casabella, T IR - Smith Casabella T FIR - Sassone, S IR - Sassone S FIR - Liberman, A IR - Liberman A FIR - Carnero, G IR - Carnero G FIR - Caccavo, A IR - Caccavo A FIR - Berli, M IR - Berli M FIR - Budassi, N IR - Budassi N FIR - Bono, J IR - Bono J FIR - Alvarisqueta, A IR - Alvarisqueta A FIR - Amerena, J IR - Amerena J FIR - Kostner, K IR - Kostner K FIR - Hamilton, A IR - Hamilton A FIR - Begg, A IR - Begg A FIR - Beltrame, J IR - Beltrame J FIR - Colquhoun, D IR - Colquhoun D FIR - Gordon, G IR - Gordon G FIR - Sverdlov, A IR - Sverdlov A FIR - Vaddadi, G IR - Vaddadi G FIR - Wong, J IR - Wong J FIR - Coller, J IR - Coller J FIR - Prior, D IR - Prior D FIR - Friart, A IR - Friart A FIR - Leone, A IR - Leone A FIR - Janssens, S IR - Janssens S FIR - Vervoort, G IR - Vervoort G FIR - Timmermans, P IR - Timmermans P FIR - Troisfontaines, P IR - Troisfontaines P FIR - Franssen, C IR - Franssen C FIR - Sarens, T IR - Sarens T FIR - Vandekerckhove, H IR - Vandekerckhove H FIR - Van De Borne, P IR - Van De Borne P FIR - Chenot, F IR - Chenot F FIR - De Sutter, J IR - De Sutter J FIR - De Vuyst, E IR - De Vuyst E FIR - Debonnaire, P IR - Debonnaire P FIR - Dupont, M IR - Dupont M FIR - Pereira Dutra, O IR - Pereira Dutra O FIR - Canani, L H IR - Canani LH FIR - Vieira Moreira, MdC IR - Vieira Moreira M FIR - de Souza, W IR - de Souza W FIR - Backes, L M IR - Backes LM FIR - Maia, L IR - Maia L FIR - De Souza Paolino, B IR - De Souza Paolino B FIR - Manenti, E R IR - Manenti ER FIR - Saporito, W IR - Saporito W FIR - Villaca Guimaraes Filho, F IR - Villaca Guimaraes Filho F FIR - Franco Hirakawa, T IR - Franco Hirakawa T FIR - Saliba, L A IR - Saliba LA FIR - Neuenschwander, F C IR - Neuenschwander FC FIR - de Freitas Zerbini, C A IR - de Freitas Zerbini CA FIR - Goncalves, G IR - Goncalves G FIR - Goncalves Mello, Y IR - Goncalves Mello Y FIR - Ascencao de Souza, J IR - Ascencao de Souza J FIR - Beck da Silva Neto, L IR - Beck da Silva Neto L FIR - Bocchi, E A IR - Bocchi EA FIR - Da Silveira, J IR - Da Silveira J FIR - de Moura Xavier Moraes Junior, J B IR - de Moura Xavier Moraes Junior JB FIR - de Souza Neto, J D IR - de Souza Neto JD FIR - Hernandes, M IR - Hernandes M FIR - Finimundi, H C IR - Finimundi HC FIR - Sampaio, C R IR - Sampaio CR FIR - Vasconcellos, E IR - Vasconcellos E FIR - Neves Mancuso, F J IR - Neves Mancuso FJ FIR - Noya Rabelo, M M IR - Noya Rabelo MM FIR - Rodrigues Bacci, M IR - Rodrigues Bacci M FIR - Santos, F IR - Santos F FIR - Vidotti, M IR - Vidotti M FIR - Simoes, M V IR - Simoes MV FIR - Gomes, F L IR - Gomes FL FIR - Vieira Nascimento, C IR - Vieira Nascimento C FIR - Precoma, D IR - Precoma D FIR - Helfenstein Fonseca, F A IR - Helfenstein Fonseca FA FIR - Ribas Fortes, J A IR - Ribas Fortes JA FIR - Leaes, P E IR - Leaes PE FIR - Campos de Albuquerque, D IR - Campos de Albuquerque D FIR - Kerr Saraiva, J F IR - Kerr Saraiva JF FIR - Rassi, S IR - Rassi S FIR - Alves da Costa, F A IR - Alves da Costa FA FIR - Reis, G IR - Reis G FIR - Zieroth, S IR - Zieroth S FIR - Dion, D IR - Dion D FIR - Savard, D IR - Savard D FIR - Bourgeois, R IR - Bourgeois R FIR - Constance, C IR - Constance C FIR - Anderson, K IR - Anderson K FIR - Verma, S IR - Verma S FIR - Leblanc, M-H IR - Leblanc MH FIR - Yung, D IR - Yung D FIR - Swiggum, E IR - Swiggum E FIR - Pliamm, L IR - Pliamm L FIR - Pesant, Y IR - Pesant Y FIR - Tyrrell, B IR - Tyrrell B FIR - Huynh, T IR - Huynh T FIR - Spiegelman, J IR - Spiegelman J FIR - Giannetti, N IR - Giannetti N FIR - Lavoie, J-P IR - Lavoie JP FIR - Hartleib, M IR - Hartleib M FIR - Bhargava, R IR - Bhargava R FIR - Straatman, L IR - Straatman L FIR - Virani, S IR - Virani S FIR - Costa-Vitali, A IR - Costa-Vitali A FIR - Hill, L IR - Hill L FIR - Heffernan, M IR - Heffernan M FIR - Khaykin, Y IR - Khaykin Y FIR - Ricci, J IR - Ricci J FIR - Senaratne, M IR - Senaratne M FIR - Zhai, A IR - Zhai A FIR - Lubelsky, B IR - Lubelsky B FIR - Toma, M IR - Toma M FIR - Yao, L IR - Yao L FIR - McKelvie, R IR - McKelvie R FIR - Noronha, L IR - Noronha L FIR - Babapulle, M IR - Babapulle M FIR - Pandey, A IR - Pandey A FIR - Curnew, G IR - Curnew G FIR - Lavoie, A IR - Lavoie A FIR - Berlingieri, J IR - Berlingieri J FIR - Kouz, S IR - Kouz S FIR - Lonn, E IR - Lonn E FIR - Chehayeb, R IR - Chehayeb R FIR - Zheng, Y IR - Zheng Y FIR - Sun, Y IR - Sun Y FIR - Cui, H IR - Cui H FIR - Fan, Z IR - Fan Z FIR - Han, X IR - Han X FIR - Jiang, X IR - Jiang X FIR - Tang, Q IR - Tang Q FIR - Zhou, J IR - Zhou J FIR - Zheng, Z IR - Zheng Z FIR - Zhang, X IR - Zhang X FIR - Zhang, N IR - Zhang N FIR - Zhang, J IR - Zhang J FIR - Zhang, Y IR - Zhang Y FIR - Shen, A IR - Shen A FIR - Yu, J IR - Yu J FIR - Ye, J IR - Ye J FIR - Yao, Y IR - Yao Y FIR - Yan, J IR - Yan J FIR - Xu, X IR - Xu X FIR - Wang, Z IR - Wang Z FIR - Ma, J IR - Ma J FIR - Li, Y IR - Li Y FIR - Li, S IR - Li S FIR - Lu, S IR - Lu S FIR - Kong, X IR - Kong X FIR - Song, Y IR - Song Y FIR - Yang, G IR - Yang G FIR - Yao, Z IR - Yao Z FIR - Zhang, J IR - Zhang J FIR - Zhang, Y IR - Zhang Y FIR - Pan, Y IR - Pan Y FIR - Guo, X IR - Guo X FIR - Sun, Z IR - Sun Z FIR - Dong, Y IR - Dong Y FIR - Zhu, J IR - Zhu J FIR - Peng, D IR - Peng D FIR - Yuan, Z IR - Yuan Z FIR - Lin, J IR - Lin J FIR - Yin, Y IR - Yin Y FIR - Jerabek, O IR - Jerabek O FIR - Burianova, H IR - Burianova H FIR - Fiala, T IR - Fiala T FIR - Hubac, J IR - Hubac J FIR - Ludka, O IR - Ludka O FIR - Monhart, Z IR - Monhart Z FIR - Vodnansky, P IR - Vodnansky P FIR - Zeman, K IR - Zeman K FIR - Foldyna, D IR - Foldyna D FIR - Krupicka, J IR - Krupicka J FIR - Podpera, I IR - Podpera I FIR - Busak, L IR - Busak L FIR - Radvan, M IR - Radvan M FIR - Vomacka, Z IR - Vomacka Z FIR - Prosecky, R IR - Prosecky R FIR - Cifkova, R IR - Cifkova R FIR - Durdil, V IR - Durdil V FIR - Vesely, J IR - Vesely J FIR - Vaclavik, J IR - Vaclavik J FIR - Cervinka, P IR - Cervinka P FIR - Linhart, A IR - Linhart A FIR - Brabec, T IR - Brabec T FIR - Miklik, R IR - Miklik R FIR - Bourhaial, H IR - Bourhaial H FIR - Olbrich, H-G IR - Olbrich HG FIR - Genth-Zotz, S IR - Genth-Zotz S FIR - Kemala, E IR - Kemala E FIR - Lemke, B IR - Lemke B FIR - Bohm, M IR - Bohm M FIR - Schellong, S IR - Schellong S FIR - Rieker, W IR - Rieker W FIR - Heitzer, T IR - Heitzer T FIR - Ince, H IR - Ince H FIR - Faghih, M IR - Faghih M FIR - Birkenfeld, A IR - Birkenfeld A FIR - Begemann, A IR - Begemann A FIR - Ghanem, A IR - Ghanem A FIR - Ujeyl, A IR - Ujeyl A FIR - von Haehling, S IR - von Haehling S FIR - Dorsel, T IR - Dorsel T FIR - Bauersachs, J IR - Bauersachs J FIR - Prull, M IR - Prull M FIR - Weidemann, F IR - Weidemann F FIR - Darius, H IR - Darius H FIR - Nickenig, G IR - Nickenig G FIR - Wilke, A IR - Wilke A FIR - Sauter, J IR - Sauter J FIR - Rauch-Kroehnert, U IR - Rauch-Kroehnert U FIR - Frey, N IR - Frey N FIR - Schulze, C P IR - Schulze CP FIR - Konig, W IR - Konig W FIR - Maier, L IR - Maier L FIR - Menzel, F IR - Menzel F FIR - Proskynitopoulos, N IR - Proskynitopoulos N FIR - Ebert, H-H IR - Ebert HH FIR - Sarnighausen, H-E IR - Sarnighausen HE FIR - Dungen, H-D IR - Dungen HD FIR - Licka, M IR - Licka M FIR - Marx, N IR - Marx N FIR - Stellbrink, C IR - Stellbrink C FIR - Winkelmann, B IR - Winkelmann B FIR - Menck, N IR - Menck N FIR - Lopez-Sendon, J L IR - Lopez-Sendon JL FIR - de la Fuente Galan, L IR - de la Fuente Galan L FIR - Delgado Jimenez, J F IR - Delgado Jimenez JF FIR - Manito Lorite, N IR - Manito Lorite N FIR - Perez de Juan Romero, M IR - Perez de Juan Romero M FIR - Galve Basilio, E IR - Galve Basilio E FIR - Cereto Castro, F IR - Cereto Castro F FIR - Gonzalez Juanatey, J R IR - Gonzalez Juanatey JR FIR - Gomez, J J IR - Gomez JJ FIR - Sanmartin Fernandez, M IR - Sanmartin Fernandez M FIR - Garcia-Moll Marimon, X IR - Garcia-Moll Marimon X FIR - Pascual Figal, D IR - Pascual Figal D FIR - Bover Freire, R IR - Bover Freire R FIR - Bonnefoy Cudraz, E IR - Bonnefoy Cudraz E FIR - Jobbe Duval, A IR - Jobbe Duval A FIR - Tomasevic, D IR - Tomasevic D FIR - Habib, G IR - Habib G FIR - Isnard, R IR - Isnard R FIR - Picard, F IR - Picard F FIR - Khanoyan, P IR - Khanoyan P FIR - Dubois-Rande, J-L IR - Dubois-Rande JL FIR - Galinier, M IR - Galinier M FIR - Roubille, F IR - Roubille F FIR - Alexandre, J IR - Alexandre J FIR - Babuty, D IR - Babuty D FIR - Delarche, N IR - Delarche N FIR - Seronde, M-F IR - Seronde MF FIR - Berneau, J-B IR - Berneau JB FIR - Girerd, N IR - Girerd N FIR - Saxena, M IR - Saxena M FIR - Rosano, G IR - Rosano G FIR - Yousef, Z IR - Yousef Z FIR - Clifford, C IR - Clifford C FIR - Arden, C IR - Arden C FIR - Bakhai, A IR - Bakhai A FIR - Squire, I IR - Squire I FIR - Boos, C IR - Boos C FIR - Jenkins, G IR - Jenkins G FIR - Travill, C IR - Travill C FIR - Price, D IR - Price D FIR - Koenyves, L IR - Koenyves L FIR - Lakatos, F IR - Lakatos F FIR - Matoltsy, A IR - Matoltsy A FIR - Noori, E IR - Noori E FIR - Zilahi, Z IR - Zilahi Z FIR - Andrassy, P IR - Andrassy P FIR - Kancz, S IR - Kancz S FIR - Simon, G IR - Simon G FIR - Sydo, T IR - Sydo T FIR - Vorobcsuk, A IR - Vorobcsuk A FIR - Merkely, B IR - Merkely B FIR - Kiss, R G IR - Kiss RG FIR - Toth, K IR - Toth K FIR - Szakal, I IR - Szakal I FIR - Nagy, L IR - Nagy L FIR - Barany, T IR - Barany T FIR - Nagy, A IR - Nagy A FIR - Szolnoki, E IR - Szolnoki E FIR - Chopra, V K IR - Chopra VK FIR - Mandal, S IR - Mandal S FIR - Rastogi, V IR - Rastogi V FIR - Shah, B IR - Shah B FIR - Mullasari, A IR - Mullasari A FIR - Shankar, J IR - Shankar J FIR - Mehta, V IR - Mehta V FIR - Oomman, A IR - Oomman A FIR - Kaul, U IR - Kaul U FIR - Komarlu, S IR - Komarlu S FIR - Kahali, D IR - Kahali D FIR - Bhagwat, A IR - Bhagwat A FIR - Vijan, V IR - Vijan V FIR - Ghaisas, N K IR - Ghaisas NK FIR - Mehta, A IR - Mehta A FIR - Kashyap, J IR - Kashyap J FIR - Kothari, Y IR - Kothari Y FIR - TaddeI, S IR - TaddeI S FIR - Scherillo, M IR - Scherillo M FIR - Zaca, V IR - Zaca V FIR - Genovese, S IR - Genovese S FIR - Salvioni, A IR - Salvioni A FIR - Fucili, A IR - Fucili A FIR - Fedele, F IR - Fedele F FIR - Cosmi, F IR - Cosmi F FIR - Volpe, M IR - Volpe M FIR - Senni, M IR - Senni M FIR - Mazzone, C IR - Mazzone C FIR - Esposito, G IR - Esposito G FIR - Doi, M IR - Doi M FIR - Yamamoto, H IR - Yamamoto H FIR - Sakagami, S IR - Sakagami S FIR - Oishi, S IR - Oishi S FIR - Yasaka, Y IR - Yasaka Y FIR - Tsuboi, H IR - Tsuboi H FIR - Fujino, Y IR - Fujino Y FIR - Matsuoka, S IR - Matsuoka S FIR - Watanabe, Y IR - Watanabe Y FIR - Himi, T IR - Himi T FIR - Ide, T IR - Ide T FIR - Ichikawa, M IR - Ichikawa M FIR - Kijima, Y IR - Kijima Y FIR - Koga, T IR - Koga T FIR - Yuda, S IR - Yuda S FIR - Fukui, K IR - Fukui K FIR - Kubota, T IR - Kubota T FIR - Manita, M IR - Manita M FIR - Fujinaga, H IR - Fujinaga H FIR - Matsumura, T IR - Matsumura T FIR - Fukumoto, Y IR - Fukumoto Y FIR - Kato, R IR - Kato R FIR - Kawai, Y IR - Kawai Y FIR - Hiasa, G IR - Hiasa G FIR - Kazatani, Y IR - Kazatani Y FIR - Mori, M IR - Mori M FIR - Ogimoto, A IR - Ogimoto A FIR - Inoko, M IR - Inoko M FIR - Oguri, M IR - Oguri M FIR - Kinoshita, M IR - Kinoshita M FIR - Okuhara, K IR - Okuhara K FIR - Watanabe, N IR - Watanabe N FIR - Ono, Y IR - Ono Y FIR - Otomo, K IR - Otomo K FIR - Sato, Y IR - Sato Y FIR - Matsunaga, T IR - Matsunaga T FIR - Takaishi, A IR - Takaishi A FIR - Miyagi, N IR - Miyagi N FIR - Uehara, H IR - Uehara H FIR - Takaishi, H IR - Takaishi H FIR - Urata, H IR - Urata H FIR - Kataoka, T IR - Kataoka T FIR - Matsubara, H IR - Matsubara H FIR - Matsumoto, T IR - Matsumoto T FIR - Suzuki, T IR - Suzuki T FIR - Takahashi, N IR - Takahashi N FIR - Imamaki, M IR - Imamaki M FIR - Watanabe, N IR - Watanabe N FIR - Yoshitama, T IR - Yoshitama T FIR - Saito, T IR - Saito T FIR - Sekino, H IR - Sekino H FIR - Furutani, Y IR - Furutani Y FIR - Koda, M IR - Koda M FIR - Matsuoka, S IR - Matsuoka S FIR - Shinozaki, T IR - Shinozaki T FIR - Hirabayashi, K IR - Hirabayashi K FIR - Tsunoda, R IR - Tsunoda R FIR - Yonezawa, K IR - Yonezawa K FIR - Hori, H IR - Hori H FIR - Yagi, M IR - Yagi M FIR - Arikawa, M IR - Arikawa M FIR - Hashizume, T IR - Hashizume T FIR - Ishiki, R IR - Ishiki R FIR - Koizumi, T IR - Koizumi T FIR - Nakayama, K IR - Nakayama K FIR - Taguchi, S IR - Taguchi S FIR - Nanasato, M IR - Nanasato M FIR - Yoshida, Y IR - Yoshida Y FIR - Tsujiyama, S IR - Tsujiyama S FIR - Nakamura, T IR - Nakamura T FIR - Oku, K IR - Oku K FIR - Shimizu, M IR - Shimizu M FIR - Suwa, M IR - Suwa M FIR - Momiyama, Y IR - Momiyama Y FIR - Sugiyama, H IR - Sugiyama H FIR - Kobayashi, K IR - Kobayashi K FIR - Inoue, S IR - Inoue S FIR - Kadokami, T IR - Kadokami T FIR - Maeno, K IR - Maeno K FIR - Kawamitsu, K IR - Kawamitsu K FIR - Maruyama, Y IR - Maruyama Y FIR - Nakata, A IR - Nakata A FIR - Shibata, T IR - Shibata T FIR - Wada, A IR - Wada A FIR - Cho, H-J IR - Cho HJ FIR - Na, J O IR - Na JO FIR - Yoo, B-S IR - Yoo BS FIR - Choi, J-O IR - Choi JO FIR - Hong, S K IR - Hong SK FIR - Shin, J-H IR - Shin JH FIR - Cho, M-C IR - Cho MC FIR - Han, S H IR - Han SH FIR - Jeong, J-O IR - Jeong JO FIR - Kim, J-J IR - Kim JJ FIR - Kang, S M IR - Kang SM FIR - Kim, D-S IR - Kim DS FIR - Kim, M H IR - Kim MH FIR - Llamas Esperon, G IR - Llamas Esperon G FIR - Illescas Diaz, J IR - Illescas Diaz J FIR - Fajardo Campos, P IR - Fajardo Campos P FIR - Almeida Alvarado, J IR - Almeida Alvarado J FIR - Bazzoni Ruiz, A IR - Bazzoni Ruiz A FIR - Echeverri Rico, J IR - Echeverri Rico J FIR - Lopez Alcocer, I IR - Lopez Alcocer I FIR - Valle Molina, L IR - Valle Molina L FIR - Hernandez Herrera, C IR - Hernandez Herrera C FIR - Calvo Vargas, C IR - Calvo Vargas C FIR - Padilla Padilla, F G IR - Padilla Padilla FG FIR - Rodriguez Briones, I IR - Rodriguez Briones I FIR - Chuquiure Valenzuela, Ejjr IR - Chuquiure Valenzuela E FIR - Aguilera Real, M E IR - Aguilera Real ME FIR - Carrillo Calvillo, J IR - Carrillo Calvillo J FIR - Alpizar Salazar, M IR - Alpizar Salazar M FIR - Cervantes Escarcega, J L IR - Cervantes Escarcega JL FIR - Velasco Sanchez, R IR - Velasco Sanchez R FIR - Al-Windy, N IR - Al-Windy N FIR - van Heerebeek, L IR - van Heerebeek L FIR - Bellersen, L IR - Bellersen L FIR - Brunner-La Rocca, H-P IR - Brunner-La Rocca HP FIR - Post, J IR - Post J FIR - Linssen, Gcm IR - Linssen G FIR - van de Wetering, M IR - van de Wetering M FIR - Peters, R IR - Peters R FIR - van Stralen, R IR - van Stralen R FIR - Groutars, R IR - Groutars R FIR - Smits, P IR - Smits P FIR - Yilmaz, A IR - Yilmaz A FIR - Kok, Wem IR - Kok W FIR - Van der Meer, P IR - Van der Meer P FIR - Dijkmans, P IR - Dijkmans P FIR - Troquay, R IR - Troquay R FIR - van Alem, A P IR - van Alem AP FIR - Van de Wal, R IR - Van de Wal R FIR - Handoko, L IR - Handoko L FIR - Westendorp, Icd IR - Westendorp I FIR - van Bergen, Pfmm IR - van Bergen P FIR - Rensing, Bjwm IR - Rensing B FIR - Hoogslag, P IR - Hoogslag P FIR - Kietselaer, B IR - Kietselaer B FIR - Kragten, J A IR - Kragten JA FIR - den Hartog, F R IR - den Hartog FR FIR - Alings, A IR - Alings A FIR - Danilowicz-Szymanowicz, L IR - Danilowicz-Szymanowicz L FIR - Raczak, G IR - Raczak G FIR - Piesiewicz, W IR - Piesiewicz W FIR - Zmuda, W IR - Zmuda W FIR - Kus, W IR - Kus W FIR - Podolec, P IR - Podolec P FIR - Musial, W IR - Musial W FIR - Drelich, G IR - Drelich G FIR - Kania, G IR - Kania G FIR - Miekus, P IR - Miekus P FIR - Mazur, S IR - Mazur S FIR - Janik, A IR - Janik A FIR - Spyra, J IR - Spyra J FIR - Peruga, J IR - Peruga J FIR - Balsam, P IR - Balsam P FIR - Krakowiak, B IR - Krakowiak B FIR - Szachniewicz, J IR - Szachniewicz J FIR - Ginel, M IR - Ginel M FIR - Grzybowski, J IR - Grzybowski J FIR - Chrustowski, W IR - Chrustowski W FIR - Wojewoda, P IR - Wojewoda P FIR - Kalinka, A IR - Kalinka A FIR - Zurakowski, A IR - Zurakowski A FIR - Koc, R IR - Koc R FIR - Debinski, M IR - Debinski M FIR - Fil, W IR - Fil W FIR - Kujawiak, M IR - Kujawiak M FIR - Forys, J IR - Forys J FIR - Kasprzak, M IR - Kasprzak M FIR - Krol, M IR - Krol M FIR - Michalski, P IR - Michalski P FIR - Mirek-Bryniarska, E IR - Mirek-Bryniarska E FIR - Radwan, K IR - Radwan K FIR - Skonieczny, G IR - Skonieczny G FIR - Stania, K IR - Stania K FIR - Skoczylas, G IR - Skoczylas G FIR - Madej, A IR - Madej A FIR - Jurowiecki, J IR - Jurowiecki J FIR - Firek, B IR - Firek B FIR - Wozakowska-Kaplon, B IR - Wozakowska-Kaplon B FIR - Cymerman, K IR - Cymerman K FIR - Neutel, J IR - Neutel J FIR - Adams, K IR - Adams K FIR - Balfour, P IR - Balfour P FIR - Deswal, A IR - Deswal A FIR - Djamson, A IR - Djamson A FIR - Duncan, P IR - Duncan P FIR - Hong, M IR - Hong M FIR - Murray, C IR - Murray C FIR - Rinde-Hoffman, D IR - Rinde-Hoffman D FIR - Woodhouse, S IR - Woodhouse S FIR - MacNevin, R IR - MacNevin R FIR - Rama, B IR - Rama B FIR - Anderson, K IR - Anderson K FIR - Broome-Webster, C IR - Broome-Webster C FIR - Kindsvater, S IR - Kindsvater S FIR - Abramov, D IR - Abramov D FIR - Barettella, M IR - Barettella M FIR - Pinney, S IR - Pinney S FIR - Herre, J IR - Herre J FIR - Cohen, A IR - Cohen A FIR - Vora, K IR - Vora K FIR - Challappa, K IR - Challappa K FIR - West, S IR - West S FIR - Baum, S IR - Baum S FIR - Cox, J IR - Cox J FIR - Jani, S IR - Jani S FIR - Karim, A IR - Karim A FIR - Akhtar, A IR - Akhtar A FIR - Quintana, O IR - Quintana O FIR - Paukman, L IR - Paukman L FIR - Goldberg, R IR - Goldberg R FIR - Bhatti, Z IR - Bhatti Z FIR - Budoff, M IR - Budoff M FIR - Bush, E IR - Bush E FIR - Potler, A IR - Potler A FIR - Delgado, R IR - Delgado R FIR - Ellis, B IR - Ellis B FIR - Dy, J IR - Dy J FIR - Fialkow, J IR - Fialkow J FIR - Sangrigoli, R IR - Sangrigoli R FIR - Ferdinand, K IR - Ferdinand K FIR - East, C IR - East C FIR - Falkowski, S IR - Falkowski S FIR - Donahoe, S IR - Donahoe S FIR - Ebrahimi, R IR - Ebrahimi R FIR - Kline, G IR - Kline G FIR - Harris, B IR - Harris B FIR - Khouzam, R IR - Khouzam R FIR - Jaffrani, N IR - Jaffrani N FIR - Jarmukli, N IR - Jarmukli N FIR - Kazemi, N IR - Kazemi N FIR - Koren, M IR - Koren M FIR - Friedman, K IR - Friedman K FIR - Herzog, W IR - Herzog W FIR - Greenberg, B IR - Greenberg B FIR - Silva Enciso, J IR - Silva Enciso J FIR - Cheung, D IR - Cheung D FIR - Grover-McKay, M IR - Grover-McKay M FIR - Hauptman, P IR - Hauptman P FIR - Mikhalkova, D IR - Mikhalkova D FIR - Hegde, V IR - Hegde V FIR - Hodsden, J IR - Hodsden J FIR - Khouri, S IR - Khouri S FIR - McGrew, F IR - McGrew F FIR - McCullough, P IR - McCullough P FIR - Littlefield, R IR - Littlefield R FIR - Bradley, P IR - Bradley P FIR - McLaurin, B IR - McLaurin B FIR - Lupovitch, S IR - Lupovitch S FIR - Labin, I IR - Labin I FIR - Rao, V IR - Rao V FIR - Leithe, M IR - Leithe M FIR - Lesko, M IR - Lesko M FIR - Lewis, N IR - Lewis N FIR - Lombardo, D IR - Lombardo D FIR - Mahal, S IR - Mahal S FIR - Malhotra, V IR - Malhotra V FIR - Mehta, V IR - Mehta V FIR - Dauber, I IR - Dauber I FIR - Banerjee, A IR - Banerjee A FIR - Needell, J IR - Needell J FIR - Miller, G IR - Miller G FIR - Paladino, L IR - Paladino L FIR - Munuswamy, K IR - Munuswamy K FIR - Nanna, M IR - Nanna M FIR - McMillan, E IR - McMillan E FIR - Mumma, M IR - Mumma M FIR - Napoli, M IR - Napoli M FIR - Nelson, W IR - Nelson W FIR - O'Brien, T IR - O'Brien T FIR - Adlakha, A IR - Adlakha A FIR - Onwuanyi, A IR - Onwuanyi A FIR - Serota, H IR - Serota H FIR - Schmedtje, J IR - Schmedtje J FIR - Paraschos, A IR - Paraschos A FIR - Potu, R IR - Potu R FIR - Sai-Sudhakar, C IR - Sai-Sudhakar C FIR - Saltzberg, M IR - Saltzberg M FIR - Sauer, A IR - Sauer A FIR - Shah, P IR - Shah P FIR - Skopicki, H IR - Skopicki H FIR - Bui, H IR - Bui H FIR - Carr, K IR - Carr K FIR - Stevens, G IR - Stevens G FIR - Tahirkheli, N IR - Tahirkheli N FIR - Tallaj, J IR - Tallaj J FIR - Yousuf, K IR - Yousuf K FIR - Trichon, B IR - Trichon B FIR - Welker, J IR - Welker J FIR - Tolerico, P IR - Tolerico P FIR - Vest, A IR - Vest A FIR - Vivo, R IR - Vivo R FIR - Wang, X IR - Wang X FIR - Abadier, R IR - Abadier R FIR - Dunlap, S IR - Dunlap S FIR - Weintraub, N IR - Weintraub N FIR - Malik, A IR - Malik A FIR - Kotha, P IR - Kotha P FIR - Zaha, V IR - Zaha V FIR - Kim, G IR - Kim G FIR - Uriel, N IR - Uriel N FIR - Greene, T IR - Greene T FIR - Salacata, A IR - Salacata A FIR - Arora, R IR - Arora R FIR - Gazmuri, R IR - Gazmuri R FIR - Kobayashi, J IR - Kobayashi J FIR - Iteld, B IR - Iteld B FIR - Vijayakrishnan, R IR - Vijayakrishnan R FIR - Dab, R IR - Dab R FIR - Mirza, Z IR - Mirza Z FIR - Marques, V IR - Marques V FIR - Nallasivan, M IR - Nallasivan M FIR - Bensimhon, D IR - Bensimhon D FIR - Peart, B IR - Peart B FIR - Saint-Jacques, H IR - Saint-Jacques H FIR - Barringhaus, K IR - Barringhaus K FIR - Contreras, J IR - Contreras J FIR - Gupta, A IR - Gupta A FIR - Koneru, S IR - Koneru S FIR - Nguyen, V IR - Nguyen V EDAT- 2021/12/04 06:00 MHDA- 2022/04/22 06:00 CRDT- 2021/12/03 20:10 PHST- 2021/08/13 00:00 [received] PHST- 2021/10/19 00:00 [revised] PHST- 2021/10/20 00:00 [accepted] PHST- 2021/12/04 06:00 [pubmed] PHST- 2022/04/22 06:00 [medline] PHST- 2021/12/03 20:10 [entrez] AID - S2213-8587(21)00292-8 [pii] AID - 10.1016/S2213-8587(21)00292-8 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2022 Jan;10(1):35-45. doi: 10.1016/S2213-8587(21)00292-8. Epub 2021 Nov 30.