diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM10374diaendo-10374Research ArticleОбзорыReviewИсходы по сердечной недостаточности у пациентов с сахарным диабетом 2-го типа: данные исследований сердечно-сосудистых исходов противодиабетических препаратовHeart failure outcomes in patients with type 2 diabetes mellitus: findings from the cardiovascular outcome trials of antidiabetes agentsAnkerStefan D.

MD, PhD, Professor, Dept of Cardiology & BCRT

s.anker@cachexia.deBerlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin; Charité UniversitätsmedizinGermany201917012020225467472Copyright © Anker S., 20192019Anker S.Anker S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/10374

Сахарный диабет 2 типа (СД2) — общепризнанный фактор риска сердечно-сосудистых заболеваний (ССЗ), включая сердечную недостаточность (СН). Данные о сердечно-сосудистом риске, ассоциированном с СД2, обусловили появление нормативного требования по проведению исследований сердечно-сосудистых исходов (ИССИ) для новых противодиабетических препаратов. За прошедшие годы несколько ИССИ различных агонистов рецепторов глюкагоноподобного пептида-1 (ГПП-1), ингибиторов дипептидилпептидазы-4 и ингибиторов натрий-глюкозного ко-транспортера-2 опубликовали данные о нейтральном или положительном влиянии на сердечно-сосудистые риски или частоту госпитализации по поводу СН. Однако эти исследования включали лишь небольшую долю пациентов с исходной СН, ограничивая тем самым имеющиеся доказательства. Продолжающиеся исследования, такие как программа EMPEROR и DAPA-HF, на больших популяциях пациентов с хронической СН могли бы расширить область применения этих препаратов за пределы их стандартных терапевтических показаний.

Type 2 diabetes mellitus (T2DM) is a recognised risk factor for several cardiovascular (CV) conditions including heart failure (HF). Findings that reflect CV risk associated with T2DM medications have led to regulatory requirement of conducting CV outcome trials (CVOTs) for new antidiabetes drugs. Over the years, several CVOTs using different glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors have reported neutral or improved CV risks or hospitalisation for HF. However, these studies included only a small proportion of the patients with baseline HF thus limiting the available evidence. Ongoing trials such as EMPEROR programme and DAPA-HF in large patient populations with chronic HF could potentially broaden the use of these drugs beyond their conventional therapeutic indication.

исследования сердечно-сосудистых исходовингибиторы ДПП-4агонисты рецепторов ГПП-1сердечная недостаточностьингибиторы НГЛТ-2сахарный диабет 2-го типаcardiovascular outcome trialsDPP-4 inhibitorsGLP-1 receptor agonistsheart failureSGLT-2 inhibitorstype 2 diabetes mellitusПубликация этой статьи поддержана Novartis Pharma AG, Базель, Швейцария.The publication of this article was supported by Novartis Pharma AG, Basel, Switzerland.ReferencesDavies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669−2701. doi: https://doi.org/10.2337/dci18-0033Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669−2701. doi: https://doi.org/10.2337/dci18-0033Emerging Risk Factors Collaboration; Di Angelantonio E, Kaptoge S, Wormser D, et al. Association of cardiometabolic multimorbidity with mortality. JAMA. 2015;314(1):52−60. doi: https://doi.org/10.1001/jama.2015.7008Emerging Risk Factors Collaboration; Di Angelantonio E, Kaptoge S, Wormser D, et al. Association of cardiometabolic multimorbidity with mortality. JAMA. 2015;314(1):52−60. doi: https://doi.org/10.1001/jama.2015.7008Zhang Y, Hu G, Yuan Z, Chen L. Glycosylated hemoglobin in relationship to cardiovascular outcomes and death in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS One. 2012;7(8):e42551. doi: https://doi.org/10.1371/journal.pone.0042551Zhang Y, Hu G, Yuan Z, Chen L. Glycosylated hemoglobin in relationship to cardiovascular outcomes and death in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS One. 2012;7(8):e42551. doi: https://doi.org/10.1371/journal.pone.0042551Kenny HC, Abel ED. Heart failure in type 2 diabetes mellitus. Circ Res. 2019;124(1):121–141. doi: https://doi.org/10.1161/circresaha.118.311371Kenny HC, Abel ED. Heart failure in type 2 diabetes mellitus. Circ Res. 2019;124(1):121–141. doi: https://doi.org/10.1161/circresaha.118.311371Cefalu WT, Kaul S, Gerstein HC. Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? Reflections from a diabetes care editors’ expert forum. Diabetes Care. 2018;41(1):14−31. doi: https://doi.org/10.2337/dci17-0057Cefalu WT, Kaul S, Gerstein HC. Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? Reflections from a diabetes care editors’ expert forum. Diabetes Care. 2018;41(1):14−31. doi: https://doi.org/10.2337/dci17-0057Guidance for industry — diabetes mellitus — evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER); 2008 [accessed on 31 July 2019]. Available from: https://www.fda.gov/media/71297/downloadGuidance for industry — diabetes mellitus — evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER); 2008 [accessed on 31 July 2019]. Available from: https://www.fda.gov/media/71297/downloadHolman RR, Sourij H, Califf RM. Cardiovascular outcome trials of glucose-lowering drugs or strategies in type 2 diabetes. Lancet. 2014;383(9933):2008–2017. doi: https://doi.org/10.1016/s0140-6736(14)60794-7Holman RR, Sourij H, Califf RM. Cardiovascular outcome trials of glucose-lowering drugs or strategies in type 2 diabetes. Lancet. 2014;383(9933):2008–2017. doi: https://doi.org/10.1016/s0140-6736(14)60794-7Schnell O, Standl E, Catrinoiu D, et al. Report from the 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group. Cardiovasc Diabetol. 2019;18(1):30. doi: https://doi.org/10.1186/s12933-019-0822-4Schnell O, Standl E, Catrinoiu D, et al. Report from the 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group. Cardiovasc Diabetol. 2019;18(1):30. doi: https://doi.org/10.1186/s12933-019-0822-4Home P. Cardiovascular outcome trials of glucose-lowering medications: an update. Diabetologia. 2019;62(3):357−369. doi: https://doi.org/10.1007/s00125-018-4801-1Home P. Cardiovascular outcome trials of glucose-lowering medications: an update. Diabetologia. 2019;62(3):357−369. doi: https://doi.org/10.1007/s00125-018-4801-1Standl E. Heart failure in diabetes: From an increased risk to a treatment target. Diabetes Mellitus. 2018;21(5):399–403. doi: https://doi.org/10.14341/dm9846Standl E. Heart failure in diabetes: From an increased risk to a treatment target. Diabetes Mellitus. 2018;21(5):399–403. doi: https://doi.org/10.14341/dm9846Hinnen D, Kruger DF. Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials. Diabetes Metab Syndr Obes. 2019;12:447−455. doi: https://doi.org/10.2147/DMSO.S188705Hinnen D, Kruger DF. Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials. Diabetes Metab Syndr Obes. 2019;12:447−455. doi: https://doi.org/10.2147/DMSO.S188705Azimova K, San Juan Z, Mukherjee D. Cardiovascular safety profile of currently available diabetic drugs. Ochsner J. 2014;14(4):616–632.Azimova K, San Juan Z, Mukherjee D. Cardiovascular safety profile of currently available diabetic drugs. Ochsner J. 2014;14(4):616–632.Castagno D, Baird-Gunning J, Jhund PS, et al. Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: evidence from a 37,229 patient meta-analysis. Am Heart J. 2011;162(5):938−948.e2. doi: https://doi.org/10.1016/j.ahj.2011.07.030Castagno D, Baird-Gunning J, Jhund PS, et al. Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: evidence from a 37,229 patient meta-analysis. Am Heart J. 2011;162(5):938−948.e2. doi: https://doi.org/10.1016/j.ahj.2011.07.030Packer M, Anker SD, Butler J, et al. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action. JAMA Cardiol. 2017;2(9):1025−1029. doi: https://doi.org/10.1001/jamacardio.2017.2275Packer M, Anker SD, Butler J, et al. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action. JAMA Cardiol. 2017;2(9):1025−1029. doi: https://doi.org/10.1001/jamacardio.2017.2275Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311−322. doi: https://doi.org/10.1056/NEJMoa1603827Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311−322. doi: https://doi.org/10.1056/NEJMoa1603827Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834−1844. doi: https://doi.org/10.1056/NEJMoa1607141Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834−1844. doi: https://doi.org/10.1056/NEJMoa1607141Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247−2257. doi: https://doi.org/10.1056/NEJMoa1509225Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247−2257. doi: https://doi.org/10.1056/NEJMoa1509225Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228−1239. doi: https://doi.org/10.1056/NEJMoa1612917Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228−1239. doi: https://doi.org/10.1056/NEJMoa1612917Green JB, Bethel MA, Armstrong PW, et al. Effect of Sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373(3):232−242. doi: https://doi.org/10.1056/NEJMoa1501352Green JB, Bethel MA, Armstrong PW, et al. Effect of Sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373(3):232−242. doi: https://doi.org/10.1056/NEJMoa1501352Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317−1326. doi: https://doi.org/10.1056/NEJMoa1307684Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317−1326. doi: https://doi.org/10.1056/NEJMoa1307684Zannad F, Cannon CP, Cushman WC, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. 2015;385(9982):2067−2076. doi: https://doi.org/10.1016/S0140-6736(14)62225-XZannad F, Cannon CP, Cushman WC, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. 2015;385(9982):2067−2076. doi: https://doi.org/10.1016/S0140-6736(14)62225-XMcInnes G, Evans M, Del Prato S, et al. Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients. Diabetes Obes Metab. 2015;17(11):1085−1092. doi: https://doi.org/10.1111/dom.12548McInnes G, Evans M, Del Prato S, et al. Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients. Diabetes Obes Metab. 2015;17(11):1085−1092. doi: https://doi.org/10.1111/dom.12548McMurray JJ, Ponikowski P, Bolli GB, et al. Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial. JACC Heart Fail. 2018;6(1):8−17. doi: https://doi.org/10.1016/j.jchf.2017.08.004McMurray JJ, Ponikowski P, Bolli GB, et al. Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial. JACC Heart Fail. 2018;6(1):8−17. doi: https://doi.org/10.1016/j.jchf.2017.08.004Packer M. Heart failure: the most important, preventable, and treatable cardiovascular complication of type 2 diabetes. Diabetes Care. 2018;41(1):11−13. doi: https://doi.org/10.2337/dci17-0052Packer M. Heart failure: the most important, preventable, and treatable cardiovascular complication of type 2 diabetes. Diabetes Care. 2018;41(1):11−13. doi: https://doi.org/10.2337/dci17-0052McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993−1004. doi: https://doi.org/10.1056/NEJMoa1409077McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993−1004. doi: https://doi.org/10.1056/NEJMoa1409077Younk LM, Lamos EM, Davis SN. Cardiovascular effects of anti-diabetes drugs. Expert Opin Drug Saf. 2016;15(9):1239−1257. doi: https://doi.org/10.1080/14740338.2016.1195368Younk LM, Lamos EM, Davis SN. Cardiovascular effects of anti-diabetes drugs. Expert Opin Drug Saf. 2016;15(9):1239−1257. doi: https://doi.org/10.1080/14740338.2016.1195368Drucker DJ. The cardiovascular biology of glucagon-like peptide-1. Cell Metab. 2016;24(1):15−30. doi: https://doi.org/10.1016/j.cmet.2016.06.009Drucker DJ. The cardiovascular biology of glucagon-like peptide-1. Cell Metab. 2016;24(1):15−30. doi: https://doi.org/10.1016/j.cmet.2016.06.009Zweck E, Roden M. GLP-1 receptor agonists and cardiovascular disease: drug-specific or class effects? Lancet Diab Endocinol. 2019;7(2):89–90. doi: https://doi.org/10.1016/s2213-8587(18)30351-6Zweck E, Roden M. GLP-1 receptor agonists and cardiovascular disease: drug-specific or class effects? Lancet Diab Endocinol. 2019;7(2):89–90. doi: https://doi.org/10.1016/s2213-8587(18)30351-6Maack C, Lehrke M, Backs J, et al. Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology. Eur Heart J. 2018;39(48):4243−4254. doi: https://doi.org/10.1093/eurheartj/ehy596Maack C, Lehrke M, Backs J, et al. Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology. Eur Heart J. 2018;39(48):4243−4254. doi: https://doi.org/10.1093/eurheartj/ehy596Anker SD, Butler J. Empagliflozin, calcium, and SGLT1/2 receptor affinity: another piece of the puzzle. ESC Heart Fail. 2018;5(4):549−551. doi: https://doi.org/10.1002/ehf2.12345Anker SD, Butler J. Empagliflozin, calcium, and SGLT1/2 receptor affinity: another piece of the puzzle. ESC Heart Fail. 2018;5(4):549−551. doi: https://doi.org/10.1002/ehf2.12345Sano M. Mechanism by which dipeptidyl peptidase-4 inhibitors increase the risk of heart failure and possible differences in heart failure risk. J Cardiol. 2019;73(1):28−32. doi: https://doi.org/10.1016/j.jjcc.2018.07.004Sano M. Mechanism by which dipeptidyl peptidase-4 inhibitors increase the risk of heart failure and possible differences in heart failure risk. J Cardiol. 2019;73(1):28−32. doi: https://doi.org/10.1016/j.jjcc.2018.07.004Kosiborod M, Cavender MA, Fu AZ, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: The CVD-REAL study (comparative effectiveness of cardiovascular outcomes in new users of sodium-glucose cotransporter-2 inhibitors). Circulation. 2017;136(3):249−259. doi: https://doi.org/10.1161/CIRCULATIONAHA.117.029190Kosiborod M, Cavender MA, Fu AZ, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: The CVD-REAL study (comparative effectiveness of cardiovascular outcomes in new users of sodium-glucose cotransporter-2 inhibitors). Circulation. 2017;136(3):249−259. doi: https://doi.org/10.1161/CIRCULATIONAHA.117.029190Kosiborod M, Lam CSP, Kohsaka S, et al.; CVD-REAL Investigators and Study Group. Lower cardiovascular risk associated with SGLT-2i in >400,000 patients: the CVD-REAL 2 study. J Am Coll Cardiol. 2018. doi: https://doi.org/10.1016/j.jacc.2018.03.009Kosiborod M, Lam CSP, Kohsaka S, et al.; CVD-REAL Investigators and Study Group. Lower cardiovascular risk associated with SGLT-2i in >400,000 patients: the CVD-REAL 2 study. J Am Coll Cardiol. 2018. doi: https://doi.org/10.1016/j.jacc.2018.03.009Suissa S. Reduced mortality with sodium-glucose cotransporter-2 inhibitors in observational studies: avoiding immortal time bias. Circulation. 2018;137(14):1432−1434. doi: https://doi.org/10.1161/CIRCULATIONAHA.117.032799Suissa S. Reduced mortality with sodium-glucose cotransporter-2 inhibitors in observational studies: avoiding immortal time bias. Circulation. 2018;137(14):1432−1434. doi: https://doi.org/10.1161/CIRCULATIONAHA.117.032799Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(21):2099. doi: https://doi.org/10.1056/NEJMc1712572Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(21):2099. doi: https://doi.org/10.1056/NEJMc1712572Wiviott SD, Raz I, Sabatine MS. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. Reply. N Engl J Med. 2019;380(19):1881−1882. doi: https://doi.org/10.1056/NEJMc1902837Wiviott SD, Raz I, Sabatine MS. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. Reply. N Engl J Med. 2019;380(19):1881−1882. doi: https://doi.org/10.1056/NEJMc1902837Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117−2128. doi: https://doi.org/10.1056/NEJMoa1504720Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117−2128. doi: https://doi.org/10.1056/NEJMoa1504720Zelniker TA, Wiviot SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31−39. doi: https://doi.org/10.1016/S0140-6736(18)32590-XZelniker TA, Wiviot SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31−39. doi: https://doi.org/10.1016/S0140-6736(18)32590-XGreene SJ, Butler J. Primary prevention of heart failure in patients with type 2 diabetes mellitus. Circulation. 2019;139(2):152−154. doi: https://doi.org/10.1161/CIRCULATIONAHA.118.037599Greene SJ, Butler J. Primary prevention of heart failure in patients with type 2 diabetes mellitus. Circulation. 2019;139(2):152−154. doi: https://doi.org/10.1161/CIRCULATIONAHA.118.037599Seferovic PM, Ponikowski P, Anker SD, et al. Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of The Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019;21(10):1169−1186. doi: https://doi.org/10.1002/ejhf.1531Seferovic PM, Ponikowski P, Anker SD, et al. Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of The Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019;21(10):1169−1186. doi: https://doi.org/10.1002/ejhf.1531Anker SD, Zannad F, Butler J, et al. Design and rationale of the EMPEROR trials of, empagliflozin 10 mg once daily, in patients with chronic heart failure with reduced ejection fraction (EMPEROR-Reduced) or preserved ejection fraction (EMPEROR-Preserved). Diabetologie und Stoffwechsel. 2019;14(S01):S66. doi: https://doi.org/10.1055/s-0039-1688298.Anker SD, Zannad F, Butler J, et al. Design and rationale of the EMPEROR trials of, empagliflozin 10 mg once daily, in patients with chronic heart failure with reduced ejection fraction (EMPEROR-Reduced) or preserved ejection fraction (EMPEROR-Preserved). Diabetologie und Stoffwechsel. 2019;14(S01):S66. doi: https://doi.org/10.1055/s-0039-1688298.McMurray JJ, DeMets DL, Inzucchi SE, et al. A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). Eur J Heart Fail. 2019;21(5):665−675. doi: https://doi.org/10.1002/ejhf.1432McMurray JJ, DeMets DL, Inzucchi SE, et al. A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). Eur J Heart Fail. 2019;21(5):665−675. doi: https://doi.org/10.1002/ejhf.1432McMurray JJV, DeMets DL, Inzucchi SE, et al. The Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019;21(11):1402−1411. doi: https://doi.org/10.1002/ejhf.1548McMurray JJV, DeMets DL, Inzucchi SE, et al. The Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019;21(11):1402−1411. doi: https://doi.org/10.1002/ejhf.1548Springer J, Springer JI, Anker SD. Muscle wasting and sarcopenia in heart failure and beyond: update 2017. ESC Heart Fail. 2017;4(4):492−498. doi: https://doi.org/10.1002/ehf2.12237Springer J, Springer JI, Anker SD. Muscle wasting and sarcopenia in heart failure and beyond: update 2017. ESC Heart Fail. 2017;4(4):492−498. doi: https://doi.org/10.1002/ehf2.12237Saitoh M, Dos Santos MR, Emami A, et al. Anorexia, functional capacity, and clinical outcome in patients with chronic heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). ESC Heart Fail. 2017;4(4):448−457. doi: https://doi.org/10.1002/ehf2.12209Saitoh M, Dos Santos MR, Emami A, et al. Anorexia, functional capacity, and clinical outcome in patients with chronic heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). ESC Heart Fail. 2017;4(4):448−457. doi: https://doi.org/10.1002/ehf2.12209Lainscak M, Omersa D, Sedlar N, et al. Heart failure prevalence in the general population: SOBOTA-HF study rationale and design. ESC Heart Fail. 2019;6(5):1077−1084. doi: https://doi.org/10.1002/ehf2.12496Lainscak M, Omersa D, Sedlar N, et al. Heart failure prevalence in the general population: SOBOTA-HF study rationale and design. ESC Heart Fail. 2019;6(5):1077−1084. doi: https://doi.org/10.1002/ehf2.12496Pietrock C, von Haehling S. Sleep-disordered breathing in heart failure: facts and numbers. ESC Heart Fail. 2017;4(3):198−202. doi: https://doi.org/10.1002/ehf2.12193Pietrock C, von Haehling S. Sleep-disordered breathing in heart failure: facts and numbers. ESC Heart Fail. 2017;4(3):198−202. doi: https://doi.org/10.1002/ehf2.12193Kubota Y, Tay WT, Asai K, et al. Chronic obstructive pulmonary disease and β-blocker treatment in Asian patients with heart failure. ESC Heart Fail. 2018;5(2):297−305. doi: https://doi.org/10.1002/ehf2.12228Kubota Y, Tay WT, Asai K, et al. Chronic obstructive pulmonary disease and β-blocker treatment in Asian patients with heart failure. ESC Heart Fail. 2018;5(2):297−305. doi: https://doi.org/10.1002/ehf2.12228Hassanein M, Abdelhamid M, Ibrahim B, et al. Gender differences in Egyptian patients hospitalized with heart failure: insights from the European Society of Cardiology Heart Failure Long-Term Registry. ESC Heart Fail. 2018;5(6):1159−1164. doi: https://doi.org/10.1002/ehf2.12347Hassanein M, Abdelhamid M, Ibrahim B, et al. Gender differences in Egyptian patients hospitalized with heart failure: insights from the European Society of Cardiology Heart Failure Long-Term Registry. ESC Heart Fail. 2018;5(6):1159−1164. doi: https://doi.org/10.1002/ehf2.12347Lam CS, Doehner W, Comin-Colet J; IRON CORE Group. Iron deficiency in chronic heart failure: case-based practical guidance. ESC Heart Fail. 2018;5(5):764−771. doi: https://doi.org/10.1002/ehf2.12333Lam CS, Doehner W, Comin-Colet J; IRON CORE Group. Iron deficiency in chronic heart failure: case-based practical guidance. ESC Heart Fail. 2018;5(5):764−771. doi: https://doi.org/10.1002/ehf2.12333

The authors declare that there are no conflicts of interest present.