Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis

被引:24
作者
McEwan, Phil [1 ]
Boyce, Rebecca [1 ]
Sanchez, Juan Jose Garcia [2 ]
Sjostrom, C. David [3 ]
Stefansson, Bergur [3 ]
Nolan, Stephen [4 ]
Correa-Rotter, Ricardo [5 ]
Rossing, Peter [6 ,7 ]
Chertow, Glenn M. [8 ]
McMurray, John J., V [9 ]
Wheeler, David C. [10 ]
Heerspink, Hiddo J. L. [11 ,12 ]
机构
[1] Hlth Econ & Outcomes Res Ltd, Cardiff, Wales
[2] AstraZeneca, BioPharmaceut, Global Market Access & Pricing, Cambridge, England
[3] AstraZeneca, BioPharmaceut R&D, Late Stage Dev, Cardiovasc Renal & Metab, Gothenburg, Sweden
[4] AstraZeneca, BioPharmaceut Med, Global Med Affairs, Cambridge, England
[5] Natl Med Sci & Nutr Inst Salvador Zubiran, Dept Nephrol & Mineral Metab, Mexico City, DF, Mexico
[6] Steno Diabet Ctr Copenhagen, Herlev, Denmark
[7] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark
[8] Stanford Univ, Dept Med & Epidemiol, Sch Med, Stanford, CA 94305 USA
[9] Univ Glasgow, British Heart Fdn Cardiovasc Res Ctr, Glasgow, Lanark, Scotland
[10] UCL, Dept Renal Med, London, England
[11] Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands
[12] George Inst Global Hlth, Sydney, NSW, Australia
关键词
chronic kidney disease; dapagliflozin; dialysis; kidney transplantation; SGLT2; inhibitor; CHRONIC KIDNEY-DISEASE; POST-HOC ANALYSIS; ADVERSE OUTCOMES; DAPAGLIFLOZIN; CANAGLIFLOZIN; HYPERTENSION; PROGRESSION; PREVENTION;
D O I
10.1093/ndt/gfac280
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Background The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up. Methods A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon. We derived treatment-specific CKD stage transition matrices using DAPA-CKD trial data. We extrapolated relevant efficacy endpoints using parametric survival equations for all-cause mortality and generalized estimating equations for recurrent events. Results When extrapolated over a 10-year period, patients randomized to dapagliflozin spent more time in CKD stages 1-3 and less in stages 4-5 than placebo [0.65 (95% CrI 0.41, 0.90) and -0.23 (95% CrI -0.45, 0.00) years per patient, respectively]. Dapagliflozin prevented an estimated 83 deaths and 51 patients initiating kidney replacement therapy per 1000 patients over 10 years. Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced (19 and 39 estimated events per 1000 patients, respectively). Conclusions Adding dapagliflozin to standard therapeutic management of CKD is expected to have long-term cardiorenal benefit beyond what has been demonstrated in the DAPA-CKD trial, with patients predicted to live longer with fewer complications.
引用
收藏
页码:1260 / 1270
页数:11
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