Effect of SGLT2 Inhibitors on Discontinuation of Renin–angiotensin System Blockade: A Joint Analysis of the CREDENCE and DAPA-CKD Trials
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Effect of SGLT2 Inhibitors on Discontinuation of Renin–angiotensin System Blockade : A Joint Analysis of the CREDENCE and DAPA-CKD Trials. / Fletcher, Robert A.; Jongs, Niels; Chertow, Glenn M.; McMurray, John J.V.; Arnott, Clare; Jardine, Meg J.; Mahaffey, Kenneth W.; Perkovic, Vlado; Rockenschaub, Patrick; Rossing, Peter; Correa-Rotter, Ricardo; Toto, Robert D.; Vaduganathan, Muthiah; Wheeler, David C.; Heerspink, Hiddo J.L.; Neuen, Brendon L.
In: Journal of the American Society of Nephrology, Vol. 34, No. 12, 2023, p. 1965-1975.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effect of SGLT2 Inhibitors on Discontinuation of Renin–angiotensin System Blockade
T2 - A Joint Analysis of the CREDENCE and DAPA-CKD Trials
AU - Fletcher, Robert A.
AU - Jongs, Niels
AU - Chertow, Glenn M.
AU - McMurray, John J.V.
AU - Arnott, Clare
AU - Jardine, Meg J.
AU - Mahaffey, Kenneth W.
AU - Perkovic, Vlado
AU - Rockenschaub, Patrick
AU - Rossing, Peter
AU - Correa-Rotter, Ricardo
AU - Toto, Robert D.
AU - Vaduganathan, Muthiah
AU - Wheeler, David C.
AU - Heerspink, Hiddo J.L.
AU - Neuen, Brendon L.
N1 - Publisher Copyright: Copyright © 2023 by the American Society of Nephrology.
PY - 2023
Y1 - 2023
N2 - 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 5 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 5 0.009). Conclusions In patients with albuminuric CKD with and without type 2 diabetes, SGLT2 inhibitors facilitate the use of RAS blockade.
AB - 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 5 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 5 0.009). Conclusions In patients with albuminuric CKD with and without type 2 diabetes, SGLT2 inhibitors facilitate the use of RAS blockade.
U2 - 10.1681/ASN.0000000000000248
DO - 10.1681/ASN.0000000000000248
M3 - Journal article
C2 - 37876229
AN - SCOPUS:85178650376
VL - 34
SP - 1965
EP - 1975
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
SN - 1046-6673
IS - 12
ER -
ID: 378130174