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

Abstract

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.

Dapagliflozin in chronic kidney disease: cost-effectiveness beyond the DAPA-CKD trial

“…This analysis adapts a published Markov model for the DAPA-CKD trial population [ 27 ], which modelled disease progression by discrete eGFR-defined health states and health states for patients on kidney replacement therapy (KRT).…”

The Role of Sodium-Glucose Cotransporter-2 Inhibitors in the Treatment Paradigm of CKD in Africa: An African Association of Nephrology Panel Position Paper

“…In addition, dapagliflozin treatment prevented 83 deaths and initiation of kidney replacement therapy in 51 cases per 1000 patients over 10 years with a reduction in predicted rates of hospitalizations due to HF and instances of sudden decline in kidney function by 19 and 39 estimated events per 1000 patients, respectively. 82 The EMPA-KIDNEY trial included adults with or without T2DM with eGFR of 20 to 45 ml/min per 1.73 m 2 , regardless of albuminuria or eGFR of 45 to 90 ml/min per 1.73 m 2 with UACR ≥200 mg/g on maximally-tolerated RAAS blockade. 61 , 83 , 84 Unlike the DAPA-CKD trial, the EMPA-KIDNEY encompassed a larger representation of patients within the G2A2 CKD subgroup, thereby extending the SGLT2i intervention to patients with lower risk and higher eGFR.…”

Mind the gap in kidney care: Translating what we know into what we do

“…The addition of SGLT2 inhibitor to renin-angiotensin-aldosterone system inhibitors could delay the need for kidney replacement therapy by several years, depending on when they are started (Fernández-Fernandez et al, 2023). Moreover, for every 1000 patients with CKD treated with an SGLT2 inhibitor on top of standard therapy, 83 deaths, 19 heart failure hospitalizations, 51 dialysis initiations and 39 episodes of acute kidney function worsening can be prevented (McEwan et al, 2023).…”