TY - JOUR
T1 - Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications
T2 - DAPA-CKD Trial
AU - Dapa-Ckd Trial Committees Investigators
AU - Chertow, Glenn M.
AU - Correa-Rotter, Ricardo
AU - Vart, Priya
AU - Jongs, Niels
AU - McMurray, John J.V.
AU - Rossing, Peter
AU - Langkilde, Anna Maria
AU - Sjöström, C. David
AU - Toto, Robert D.
AU - Wheeler, David C.
AU - Heerspink, Hiddo J.L.
N1 - Publisher Copyright:
© 2023 The Authors and AstraZeneca. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2023/5/2
Y1 - 2023/5/2
N2 - BACKGROUND: The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. METHODS AND RESULTS: We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m2 and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin-angiotensin-aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin-angiotensin-aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β-adrenergic antagonists (39.0%), diuretics (43.7%), and an-tithrombotic (47.4%), and lipid-lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. CONCLUSIONS: The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications.
AB - BACKGROUND: The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. METHODS AND RESULTS: We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m2 and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin-angiotensin-aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin-angiotensin-aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β-adrenergic antagonists (39.0%), diuretics (43.7%), and an-tithrombotic (47.4%), and lipid-lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. CONCLUSIONS: The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications.
KW - SGLT2 inhibitors
KW - cardiovascular medications
KW - chronic kidney disease
KW - dapagliflozin
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U2 - 10.1161/JAHA.122.028739
DO - 10.1161/JAHA.122.028739
M3 - Article
C2 - 37119064
AN - SCOPUS:85159542692
SN - 2047-9980
VL - 12
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 9
M1 - e028739
ER -