Fletcher, Robert A;
Jongs, Niels;
Chertow, Glenn M;
McMurray, John JV;
Arnott, Clare;
Jardine, Meg J;
Mahaffey, Kenneth W;
... Neuen, Brendon L; + view all
(2023)
Effect of SGLT2 Inhibitors on Discontinuation of Renin–angiotensin System Blockade: A Joint Analysis of the CREDENCE and DAPA-CKD Trials.
Journal of the American Society of Nephrology
, 34
(12)
pp. 1965-1975.
10.1681/ASN.0000000000000248.
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Abstract
Background: Strategies to enable persistent use of renin–angiotensin system (RAS) blockade to improve outcomes in CKD have long been sought. The effect of SGLT2 inhibitors on discontinuation of RAS blockade has yet to be evaluated. // Methods: We conducted a joint analysis of canagliflozin and renal events in diabetes with established nephropathy clinical evaluation (CREDENCE) and dapagliflozin and prevention of adverse outcomes in CKD (DAPA-CKD), two randomized, double-blind, placebo-controlled, event-driven trials of SGLT2 inhibitors in patients with albuminuric CKD. The main outcome was time to incident temporary or permanent discontinuation of RAS blockade, defined as interruption of an ACE inhibitor or ARB for at least 4 weeks or complete cessation during the double-blind on-treatment period. Cox regression analyses were used to estimate the treatment effects from each trial. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were pooled with fixed effects meta-analysis to obtain summary treatment effects, overall and across key subgroups. // Results: During median follow-up of 2.2 years across both trials, 740 of 8483 (8.7%) patients discontinued RAS blockade. The relative risk for discontinuation of RAS blockade was 15% lower in patients randomized to receiving SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74 to 0.99), with consistent effects across trials (P-heterogeneity = 0.92). The relative effect on RAS blockade discontinuation was more pronounced among patients with baseline urinary albumin:creatinine ratio ≥1000 mg/g (pooled HR, 0.77; 95% CI, 0.63 to 0.94; P-heterogeneity = 0.009). // Conclusions: In patients with albuminuric CKD with and without type 2 diabetes, SGLT2 inhibitors facilitate the use of RAS blockade.
| Type: | Article |
|---|---|
| Title: | Effect of SGLT2 Inhibitors on Discontinuation of Renin–angiotensin System Blockade: A Joint Analysis of the CREDENCE and DAPA-CKD Trials |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1681/ASN.0000000000000248 |
| Publisher version: | https://doi.org/10.1681/ASN.0000000000000248 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | CKD; randomized controlled trials; renin–angiotensin system; SGLT2 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10182172 |
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