Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF

. 2020 Sep 15 ; 142 (11) : 1040-1054. [epub] 20200716

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid32673497

Grantová podpora
FS/18/14/33330 British Heart Foundation - United Kingdom
RE/18/6/34217 British Heart Foundation - United Kingdom

BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

2nd Department of Internal Medicine Cardiovascular Medicine General Teaching Hospital and 1st Faculty of Medicine Charles University Prague Czech Republic

5th Department of Internal Medicine Comenius University in Bratislava Slovakia

BHF Cardiovascular Research Centre University of Glasgow UK

Cardiovascular Renal and Metabolism Translational Medicines Unit Early Clinical Development IMED Biotech Unit AstraZeneca Gothenburg Sweden

Clinic of Cardiology National Cardiology Hospital Sofia Bulgaria

Cumming School of Medicine and Libin Cardiovascular Institute University of Calgary AB Canada

Department of Biostatistics and Medical Informatics University of Wisconsin Madison

Department of Cardiology Medanta Gurgaon India

Department of Cardiology Montreal Heart Institute QC Canada

Department of Cardiology University Medical Center and University of Groningen The Netherlands

Department of Cardiology University of Minnesota Minneapolis

Department of Medicine Saarland University Hospital Homburg Saar Germany

Department of Molecular and Clinical Medicine and Cardiology Sahlgrenska Academy Gothenburg Sweden

Department of Myocardial Disease and Heart Failure National Medical Research Center of Cardiology Moscow Russia

Division of Cardiac Surgery St Michael's Hospital University of Toronto ON Canada

Division of Cardiovascular Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA

Late Stage Development Cardiovascular Renal and Metabolism BioPharmaceuticals R and D AstraZeneca Gothenburg Sweden

National University of Cordoba Argentina

Quantitative Clinical Pharmacology IMED Biotech Unit Astra Zeneca Gaithersburg MD

Rigshospitalet Copenhagen University Hospital Denmark

Saint Luke's Mid America Heart Institute University of Missouri Kansas City

Section of Endocrinology Yale University School of Medicine New Haven CT

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Sattar N, McLaren J, Kristensen SL, Preiss D, McMurray JJ. SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms? Diabetologia. 2016; 59:1333–1339. doi: 10.1007/s00125-016-3956-x PubMed PMC

McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, et al. ; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019; 381:1995–2008. doi: 10.1056/NEJMoa1911303 PubMed

McMurray JJV, DeMets DL, Inzucchi SE, Køber L, Kosiborod MN, Langkilde AM, Martinez FA, Bengtsson O, Ponikowski P, Sabatine MS, et al. ; DAPA-HF Committees and Investigators. 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; 21:665–675. doi: 10.1002/ejhf.1432 PubMed PMC

Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, et al. ; Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Investigators and Committees. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004; 110:2618–2626. doi: 10.1161/01.CIR.0000146819.43235.A9 PubMed

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, et al. ; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371:993–1004. doi: 10.1056/NEJMoa1409077 PubMed

Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011; 364:11–21. doi: 10.1056/NEJMoa1009492 PubMed

Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010; 376:875–885. doi: 10.1016/S0140-6736(10)61198-1 PubMed

Maggioni AP, Anker SD, Dahlström U, Filippatos G, Ponikowski P, Zannad F, Amir O, Chioncel O, Leiro MC, Drozdz J, et al. ; Heart Failure Association of the ESC. Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2013; 15:1173–1184. doi: 10.1093/eurjhf/hft134 PubMed

Teng TK, Tromp J, Tay WT, Anand I, Ouwerkerk W, Chopra V, Wander GS, Yap JJ, MacDonald MR, Xu CF, et al. ; ASIAN-HF investigators. Prescribing patterns of evidence-based heart failure pharmacotherapy and outcomes in the ASIAN-HF registry: a cohort study. Lancet Glob Health. 2018; 6:e1008–e1018. doi: 10.1016/S2214-109X(18)30306-1 PubMed

Parén P, Dahlström U, Edner M, Lappas G, Rosengren A, Schaufelberger M. Association of diuretic treatment at hospital discharge in patients with heart failure with all-cause short- and long-term mortality: a propensity score-matched analysis from SwedeHF. Int J Cardiol. 2018; 257:118–124. doi: 10.1016/j.ijcard.2017.09.193 PubMed

Vardeny O, Claggett B, Kachadourian J, Desai AS, Packer M, Rouleau J, Zile MR, Swedberg K, Lefkowitz M, Shi V, et al. Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial. Eur J Heart Fail. 2019; 21:337–341. doi: 10.1002/ejhf.1402 PubMed PMC

Brunner-La Rocca H-P, Linssen GC, Smeele FJ, van Drimmelen AA, Schaafsma H-J, Westendorp PH, Rademaker PC, van de Kamp HJ, Hoes AW, Brugts JJ. Contemporary drug treatment of chronic heart failure with reduced ejection fraction: the CHECK-HF Registry. JACC Hear Fail. 2019; 7:13–21. doi: 10.1016/j.jchf.2018.10.010 PubMed

DeVore AD, Mi X, Thomas L, Sharma PP, Albert NM, Butler J, Hernandez AF, Patterson JH, Spertus JA, Williams FB, et al. Characteristics and treatments of patients enrolled in the CHAMP-HF Registry compared with patients enrolled in the PARADIGM-HF Trial. J Am Heart Assoc. 2018; 7:e009237 doi: 10.1161/JAHA.118.009237 PubMed PMC

Jankowska EA, Kalicinska E, Drozd M, Kurian B, Banasiak W, Ponikowski P. Comparison of clinical profile and management of outpatients with heart failure with reduced left ventricular ejection fraction treated by general practitioners and cardiologists in contemporary Poland: the results from the DATA-HELP registry. Int J Cardiol. 2014; 176:852–858. doi: 10.1016/j.ijcard.2014.08.005 PubMed

Fudim M, O’Connor CM, Mulder H, Coles A, Bhatt AS, Ambrosy AP, Kraus WE, Piña IL, Whellan DJ, Mentz RJ. Loop diuretic adjustments in patients with chronic heart failure: insights from HF-ACTION. Am Heart J. 2018; 205:133–141. doi: 10.1016/j.ahj.2018.06.017 PubMed PMC

Sha S, Polidori D, Heise T, Natarajan J, Farrell K, Wang SS, Sica D, Rothenberg P, Plum-Mörschel L. Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2014; 16:1087–1095. doi: 10.1111/dom.12322 PubMed

List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009; 32:650–657. doi: 10.2337/dc08-1863 PubMed PMC

Wilcox CS, Shen W, Boulton DW, Leslie BR, Griffen SC. Interaction between the sodium-glucose-linked transporter 2 inhibitor dapagliflozin and the loop diuretic bumetanide in normal human subjects. J Am Heart Assoc. 2018; 7:e007046 doi: 10.1161/JAHA.117.007046 PubMed PMC

Damman K, Ter Maaten JM, Coster JE, Krikken JA, Deursen VM, Krijnen HK, Hofman M, Nieuwland W, Veldhuisen DJ, Voors AA, et al. Clinical importance of urinary sodium excretion in acute heart failure [published online February 22, 2020]. Eur J Heart Fail. doi:10.1002/ejhf.1753. https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.1753 PubMed DOI PMC

Hallow KM, Helmlinger G, Greasley PJ, McMurray JJV, Boulton DW. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obes Metab. 2018; 20:479–487. doi: 10.1111/dom.13126 PubMed

Karg MV, Bosch A, Kannenkeril D, Striepe K, Ott C, Schneider MP, Boemke-Zelch F, Linz P, Nagel AM, Titze J, et al. SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomised controlled trial. Cardiovasc Diabetol. 2018; 17:5 doi: 10.1186/s12933-017-0654-z PubMed PMC

Lambers Heerspink HJ, de Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013; 15:853–862. doi: 10.1111/dom.12127 PubMed PMC

Mazer CD, Hare GMT, Connelly PW, Gilbert RE, Shehata N, Quan A, Teoh H, Leiter LA, Zinman B, Jüni P, et al. Effect of empagliflozin on erythropoietin levels, iron stores, and red blood cell morphology in patients with type 2 diabetes mellitus and coronary artery disease. Circulation. 2020; 141:704–707. doi: 10.1161/CIRCULATIONAHA.119.044235 PubMed

Ghanim H, Abuaysheh S, Hejna J, Green K, Batra M, Makdissi A, Chaudhuri A, Dandona P. Dapagliflozin suppresses hepcidin and increases erythropoiesis. J Clin Endocrinol Metab. 2020; 105:dgaa057 doi: 10.1210/clinem/dgaa057 PubMed

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