Cardiovascular and renal outcomes with canagliflozin according to baseline kidney function data from the CANVAS program

Circulation

Volumn 138, Issue 15, 2018, Pages 1537-1550

  Neuen, Brendon L ^a   Ohkuma, Toshiaki ^a   Neal, Bruce ^a   Matthews, David R ^b   De Zeeuw, Dick ^c   Mahaffey, Kenneth W ^d   Fulcher, Greg ^e   Desai, Mehul ^f   Li, Qiang ^a   Deng, Hsiaowei ^f   Rosenthal, Norm ^f   Jardine, Meg J ^a,g   Bakris, George ^h   Perkovic, Vlado ^a,e  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^d STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e ROYAL NORTH SHORE HOSPITAL   (Australia)

^f JANSSEN RESEARCH AND DEVELOPMENT   (United States)

^g Department of Microbiology and Infectious Diseases   (Australia)

^h UNIVERSITY OF CHICAGO MEDICAL CENTER   (United States)

Author keywords

Canagliflozin; Cardiovascular diseases; Chronic; Diabetes mellitus; Glomerular filtration rate; Kidney; Renal insufficiency; Sodium glucose cotransporter 2; Treatment outcome; Type 2

Indexed keywords

ANTIHYPERTENSIVE AGENT; CANAGLIFLOZIN; CREATININE; GLUCOSE; HEMOGLOBIN A1C; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; TRIACYLGLYCEROL;

ADULT; AGED; ALBUMINURIA; ARTICLE; BLOOD PRESSURE; BRAIN ISCHEMIA; CARDIOVASCULAR DISEASE; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CHRONIC KIDNEY FAILURE; CORONARY ARTERY ATHEROSCLEROSIS; DRUG SAFETY; END STAGE RENAL DISEASE; ESTIMATED GLOMERULAR FILTRATION RATE; FEMALE; HEART FAILURE; HEART INFARCTION; HUMAN; HYPOGLYCEMIA; KIDNEY DISEASE; KIDNEY FUNCTION; MACROALBUMINURIA; MAJOR CLINICAL STUDY; MALE; MICROALBUMINURIA; MIDDLE AGED; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROTEINURIA; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; SYSTOLIC BLOOD PRESSURE; ADVERSE EVENT; CARDIOVASCULAR SYSTEM; CLINICAL DECISION MAKING; DRUG EFFECT; GLOMERULUS FILTRATION RATE; KIDNEY; MORTALITY; MULTICENTER STUDY (TOPIC); PATHOPHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK ASSESSMENT; RISK FACTOR; TIME FACTOR; TREATMENT OUTCOME;

AGED; CANAGLIFLOZIN; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; CLINICAL DECISION-MAKING; DIABETES MELLITUS, TYPE 2; FEMALE; GLOMERULAR FILTRATION RATE; HUMANS; KIDNEY; MALE; MIDDLE AGED; MULTICENTER STUDIES AS TOPIC; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RENAL INSUFFICIENCY, CHRONIC; RISK ASSESSMENT; RISK FACTORS; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS; TIME FACTORS; TREATMENT OUTCOME;

EID: 85053770094     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.118.035901     Document Type: Article

References (32)

1. Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK and Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215-2222. doi 10.1016/S0140-6736(10)60484-9
2. Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, de Boer IH. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24:302-308. doi: 10.1681/ASN.2012070718
3. 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
4. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; on behalf of the CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644-657. doi 10.1056/NEJMoa1611925
5. 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
6. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC and Zinman B. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323-334. doi 10.1056/NEJMoa1515920
7. Petrykiv S, Sjostrom CD, Greasley PJ, Xu J, Persson F and Heerspink HJL. Differential effects of dapagliflozin on cardiovascular risk factors at varying degrees of renal function. Clin J Am Soc Nephrol. 2017;12:751-759. doi 10.2215/CJN.10180916
8. Cherney DZI, Cooper ME, Tikkanen I, Pfarr E, Johansen OE, Woerle HJ, Broedl UC, Lund SS. Pooled analysis of Phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int. 2018;93:231-244. doi: 10.1016/j.kint.2017.06.017
9. Hinnen D. Glucuretic effects and renal safety of dapagliflozin in patients with type 2 diabetes. Ther Adv Endocrinol Metab. 2015;6:92-102. doi: 10.1177/2042018815575273
10. Scheen AJ. Pharmacokinetics, pharmacodynamics and clinical use of SGLT2 inhibitors in patients with type 2 diabetes mellitus and chronic kidney disease. Clin Pharmacokinet. 2015;54:691-708. doi: 10.1007/s40262-015-0264-4
11. Seidu S, Kunutsor SK, Cos X, Gillani S, Khunti K; for and on behalf of Primary Care Diabetes Europe. SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: a systematic review and meta-analysis. Prim Care Diabetes. 2018;12:265-283. doi: 10.1016/j.pcd.2018.02.001
12. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296-1305. doi: 10.1056/NEJMoa041031
13. Fine JP and Gray RJ. A proportional hazards model for the subdistri-bution of a competing risk. J Am Stat Assoc. 1999;94:496-509. doi 10.1080/01621459.1999.10474144
14. Altman DG, Andersen PK. Calculating the number needed to treat for trials where the outcome is time to an event. BMJ. 1999;319:1492-1495.
15. Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Erondu N, Shaw W, Barrett TD, Weidner-Wells M, Deng H, Rosenthal N, Desai M, Matthews DR, Neal B. Canagliflozin and renal outcomes in type 2 diabetes: data from the CANVAS randomized clinical trial program. Lancet Diabetes Endocrinol. 2018; In press. doi 10.1016/S2213-8587(18)30141-4
16. Sha S, Devineni D, Ghosh A, Polidori D, Chien S, Wexler D, Shalayda K, Demarest K, Rothenberg P. Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects. Diabetes Obes Metab. 2011;13:669-672. doi: 10.1111/j.1463-1326.2011.01406.x
17. Liang Y, Arakawa K, Ueta K, Matsushita Y, Kuriyama C, Martin T, Du F, Liu Y, Xu J, Conway B, Conway J, Polidori D, Ways K and Demarest K. Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PLoS ONE. 2012;7:e30555. doi 10.1371/journal.pone.0030555
18. 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
19. Heerspink HJ, Desai M, Jardine M, Balis D, Meininger G, Perkovic V. Canagliflozin slows progression of renal function decline independently of glycemic effects. J Am Soc Nephrol. 2017;28:368-375. doi: 10.1681/ASN.2016030278
20. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC, Jr., Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH, Jr., Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559. doi 10.1056/NEJMoa0802743
21. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-139. doi: 10.1056/NEJMoa0808431
22. Plutzky J, Bakris G. Sodium/glucose cotransporter 2 inhibitors in patients with diabetes mellitus and chronic kidney disease: turning the page. Circulation. 2018;137:130-133. doi: 10.1161/CIRCULATIONAHA.117.031422
23. Hung SC, Kuo KL, Peng CH, Wu CH, Lien YC, Wang YC and Tarng DC. Volume overload correlates with cardiovascular risk factors in patients with chronic kidney disease. Kidney Int. 2014;85:703-709. doi 10.1038/ki.2013.336
24. 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
25. Ferrannini E, Mark M and Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a “thrifty substrate” hypothesis. Diabetes Care. 2016;39:1108-1114. doi 10.2337/dc16-0330
26. Bell RM, Yellon DM. SGLT2 inhibitors: hypotheses on the mechanism of cardiovascular protection. Lancet Diabetes Endocrinol. 2018;6:435-437. doi: 10.1016/S2213-8587(17)30314-5
27. 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
28. Jardine MJ, Mahaffey KW, Neal B, Agarwal R, Bakris GL, Brenner BM, Bull S, Cannon CP, Charytan DM, de Zeeuw D, Edwards R, Greene T, Heerspink HJL, Levin A, Pollock C, Wheeler DC, Xie J, Zhang H, Zinman B, Desai M, Perkovic V; CREDENCE study investigators. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. Am J Nephrol. 2017;46:462-472. doi: 10.1159/000484633
29. Pecoits-Filho R, Perkovic V. Are SGLT2 inhibitors ready for prime time for CKD? Clin J Am Soc Nephrol. 2018;13:318-320. doi: 10.2215/CJN.07680717
30. Boehringer Ingelheim. Boehringer Ingelheim and Lilly announce an academic collaboration with University of Oxford to investigate the effects of empagliflozin in people with chronic kidney disease. https://www.boehringer-ingelheim.com/EMPA-KIDNEY. Accessed May 22, 2018.
31. Tonelli M, Agarwal S, Cass A, Garcia Garcia G, Jha V, Naicker S, Wang H, Yang CW, O'Donoghue D. How to advocate for the inclusion of chronic kidney disease in a national noncommunicable chronic disease program. Kidney Int. 2014;85:1269-1274. doi 10.1038/ki.2012.488
32. Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116:85-97. doi: 10.1161/CIRCULATIONAHA.106.678342