Empagliflozin improves kidney outcomes in patients with or without heart failure insights from the Empa-Reg OUTCOME trial

Circulation: Heart Failure

Volumn 12, Issue 6, 2019, Pages

  Butler, Javed ^a   Zannad, Faiez ^b   Fitchett, David ^c   Zinman, Bernard ^d   Koitka Weber, Audrey ^e,f,g   Von Eynatten, Maximilian ^e   Zwiener, Isabella ^e   George, Jyothis ^e   Brueckmann, Martina ^e,h   Cheung, Alfred K ⁱ   Wanner, Christoph ^g  

^a UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

^b Department of Cardiovascular Surgery Institut Lorrain du Coeur et des Vaisseaux   (France)

^c ST MICHAEL'S HOSPITAL   (Canada)

^d MOUNT SINAI HOSPITAL   (Canada)

^e BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^f MONASH UNIVERSITY   (Australia)

^g UNIVERSITY OF WÜRZBURG   (Germany)

^h UNIVERSITY OF HEIDELBERG   (Germany)

ⁱ UNIVERSITY OF UTAH   (United States)

Author keywords

Cardiovascular diseases; Chronic kidney disease; Diabetes mellitus; Heart failure; Sodium glucose transporter 2; Type 2

Indexed keywords

EMPAGLIFLOZIN; ANTIDIABETIC AGENT; BENZHYDRYL DERIVATIVE; GLUCOSIDE;

ACUTE KIDNEY FAILURE; ADULT; ARTICLE; CARDIOVASCULAR MORTALITY; CHRONIC KIDNEY FAILURE; DEHYDRATION; DISEASE EXACERBATION; DRUG SAFETY; DRUG WITHDRAWAL; EDEMA; ESTIMATED GLOMERULAR FILTRATION RATE; FEMALE; GENITAL TRACT INFECTION; HEART FAILURE; HUMAN; HYPERKALEMIA; HYPOTENSION; INCIDENCE; KIDNEY FUNCTION; MACROALBUMINURIA; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; NON INSULIN DEPENDENT DIABETES MELLITUS; POST HOC ANALYSIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK REDUCTION; AGED; ALBUMINURIA; CARDIOVASCULAR DISEASE; COMPLICATION; DRUG EFFECT; GLOMERULUS FILTRATION RATE; KIDNEY; RISK FACTOR;

ADULT; AGED; ALBUMINURIA; BENZHYDRYL COMPOUNDS; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; FEMALE; GLOMERULAR FILTRATION RATE; GLUCOSIDES; HEART FAILURE; HUMANS; HYPOGLYCEMIC AGENTS; KIDNEY; MALE; MIDDLE AGED; RISK FACTORS; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS;

EID: 85067519150     PISSN: 19413289     EISSN: 19413297     Source Type: Journal    
DOI: 10.1161/CIRCHEARTFAILURE.118.005875     Document Type: Article

References (23)

1. Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, Nodari S, Lam CSP, Sato N, Shah AN, Gheorghiade M. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63:1123–1133. doi: 10.1016/j.jacc.2013.11.053
2. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18:891–975. doi: 10.1002/ejhf.592
3. Seferović PM, Petrie MC, Filippatos GS, Anker SD, Rosano G, Bauersachs J, Paulus WJ, Komajda M, Cosentino F, de Boer RA, Farmakis D, Doehner W, Lambrinou E, Lopatin Y, Piepoli MF, Theodorakis MJ, Wiggers H, Lekakis J, Mebazaa A, Mamas MA, Tschöpe C, Hoes AW, Seferović JP, Logue J, McDonagh T, Riley JP, Milinković I, Polovina M, van Veldhuisen DJ, Lainscak M, Maggioni AP, Ruschitzka F, McMurray JJV. Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018;20:853–872. doi: 10.1002/ejhf.1170
4. Fitchett D, Butler J, van de Borne P, Zinman B, Lachin JM, Wanner C, Woerle HJ, Hantel S, George JT, Johansen OE, Inzucchi SE; EMPA-REG OUTCOME® Trial Investigators. Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOME® trial. Eur Heart J. 2018;39:363–370. doi: 10.1093/eurheartj/ehx511
5. McAllister DA, Read SH, Kerssens J, Livingstone S, McGurnaghan S, Jhund P, Petrie J, Sattar N, Fischbacher C, Kristensen SL, McMurray J, Colhoun HM, Wild SH. Incidence of hospitalization for heart failure and case-fatality among 3.25 million people with and without diabetes mellitus. Circulation. 2018;138:2774–2786. doi: 10.1161/CIRCULATIONAHA.118.034986
6. van Deursen VM, Urso R, Laroche C, Damman K, Dahlström U, Tavazzi L, Maggioni AP, Voors AA. Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey. Eur J Heart Fail. 2014;16:103–111. doi: 10.1002/ejhf.30
7. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128. doi: 10.1056/NEJMoa1504720
8. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–334. doi: 10.1056/NEJMoa1515920
9. Fitchett D, Zinman B, Wanner C, Lachin JM, Hantel S, Salsali A, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME® Trial Investigators. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J. 2016;37:1526–1534. doi: 10.1093/eurheartj/ehv728
10. Zinman B, Inzucchi SE, Lachin JM, Wanner C, Ferrari R, Fitchett D, Bluhmki E, Hantel S, Kempthorne-Rawson J, Newman J, Johansen OE, Woerle HJ, Broedl UC. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™). Cardiovasc Diabetol. 2014;13:102. doi: 10.1186/1475-2840-13-102
11. Wanner C, Heerspink HJL, Zinman B, Inzucchi SE, Koitka-Weber A, Mattheus M, Hantel S, Woerle HJ, Broedl UC, von Eynatten M, Groop PH; EMPA-REG OUTCOME Investigators. Empagliflozin and kidney function decline in patients with type 2 diabetes: a slope analysis from the EM-PA-REG OUTCOME Trial. J Am Soc Nephrol. 2018;29:2755–2769. doi: 10.1681/ASN.2018010103
12. Cherney DZI, Zinman B, Inzucchi SE, Koitka-Weber A, Mattheus M, von Eynatten M, Wanner C. Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5:610–621. doi: 10.1016/S2213-8587(17)30182-1
13. Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, Fagan NM, Woerle HJ, Johansen OE, Broedl UC, von Eynatten M. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129:587–597. doi: 10.1161/CIRCULATIONAHA.113.005081
14. Skrtić M, Yang GK, Perkins BA, Soleymanlou N, Lytvyn Y, von Eynatten M, Woerle HJ, Johansen OE, Broedl UC, Hach T, Silverman M, Cherney DZ. Characterisation of glomerular haemodynamic responses to SGLT2 inhibition in patients with type 1 diabetes and renal hyperfiltration. Diabetolo-gia. 2014;57:2599–2602. doi: 10.1007/s00125-014-3396-4
15. Damman K, Gori M, Claggett B, Jhund PS, Senni M, Lefkowitz MP, Prescott MF, Shi VC, Rouleau JL, Swedberg K, Zile MR, Packer M, Desai AS, Solomon SD, McMurray JJV. Renal effects and associated outcomes during angiotensin-neprilysin inhibition in heart failure. JACC Heart Fail. 2018;6:489–498. doi: 10.1016/j.jchf.2018.02.004
16. Butler J, Hamo CE, Filippatos G, Pocock SJ, Bernstein RA, Brueckmann M, Cheung AK, George JT, Green JB, Januzzi JL, Kaul S, Lam CSP, Lip GYH, Marx N, McCullough PA, Mehta CR, Ponikowski P, Rosenstock J, Sattar N, Salsali A, Scirica BM, Shah SJ, Tsutsui H, Verma S, Wanner C, Woerle HJ, Zannad F, Anker SD; EMPEROR Trials Program. The potential role and rationale for treatment of heart failure with sodium-glucose co-transporter 2 inhibitors. Eur J Heart Fail. 2017;19:1390–1400. doi: 10.1002/ejhf.933
17. Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. 2016;134:752–772. doi: 10.1161/CIRCULATIONAHA.116.021887
18. Verma S, McMurray JJV, Cherney DZI. The metabolodiuretic promise of sodium-dependent glucose cotransporter 2 inhibition: the search for the sweet spot in heart failure. JAMA Cardiol. 2017;2:939–940. doi: 10.1001/jamacardio.2017.1891
19. Heise T, Seewaldt-Becker E, Macha S, Hantel S, Pinnetti S, Seman L, Woerle HJ. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks’ treatment with empagliflozin once daily in patients with type 2 diabetes. Diabetes Obes Metab. 2013;15:613–621. doi: 10.1111/dom.12073
20. 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
21. Mudaliar S, Alloju S, Henry RR. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME Study? A unifying hypothesis. Diabetes Care. 2016;39:1115–1122. doi: 10.2337/dc16-0542
22. Muller ME, Pruijm M, Bonny O, Burnier M, Zanchi A. Effects of the SGLT-2 inhibitor empagliflozin on renal tissue oxygenation in non-diabetic subjects: a randomized, double-blind, placebo-controlled study protocol. Adv Ther. 2018;35:875–885. doi: 10.1007/s12325-018-0708-y
23. Wanner C, Lachin JM, Inzucchi SE, Fitchett D, Mattheus M, George J, Woerle HJ, Broedl UC, von Eynatten M, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease. Circulation. 2018;137:119–129. doi: 10.1161/CIRCULATIONAHA.117.028268