Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58



Cahn, Avivit, Raz, Itamar, Leiter, Lawrence A, Mosenzon, Ofri, Murphy, Sabina A, Goodrich, Erica L, Yanuv, Ilan, Rozenberg, Aliza, Bhatt, Deepak L, McGuire, Darren K
et al (show 5 more authors) (2021) Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58. DIABETES CARE, 44 (5). pp. 1159-1167.

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Abstract

<h4>Objective</h4>International guidelines propose prescribing sodium-glucose cotransporter 2 (SGLT2) inhibitors to patients with type 2 diabetes (T2D) as secondary prevention in patients with established atherosclerotic cardiovascular disease (ASCVD) or for primary prevention of cardiovascular events in high-risk patients with multiple risk factors (MRF) for ASCVD. The current analyses expand on the cardiovascular renal and metabolic effects of SGLT2 inhibitors in MRF patients.<h4>Research design and methods</h4>In DECLARE-TIMI 58, 17,160 patients with T2D and MRF (59.4%) or established ASCVD (40.6%) were randomized to dapagliflozin versus placebo; patients were followed for a median of 4.2 years. The cardiovascular and renal outcomes in the MRF cohort were studied across clinically relevant subgroups for treatment effect and subgroup-based treatment interaction.<h4>Results</h4>Among patients with MRF, the reduction with dapagliflozin in risk of cardiovascular death or hospitalization for heart failure (CVD/HHF) (hazard ratio [HR] 0.84, 95% CI 0.67-1.04) and the renal-specific outcome (HR 0.51, 95% CI 0.37-0.69) did not differ from that for patients with ASCVD (<i>P</i> <sub>interaction</sub> 0.99 and 0.72, respectively). The effect on CVD/HHF was entirely driven by a reduction in HHF (HR 0.64, 95% CI 0.46-0.88). The benefits of dapagliflozin on HHF and on the renal-specific outcome, among the subset with MRF, were directionally consistent across clinically relevant subgroups. At 48 months, HbA<sub>1c</sub>, weight, systolic blood pressure, and urinary albumin-to-creatinine ratio were lower with dapagliflozin versus placebo and estimated glomerular filtration rate was higher (<i>P</i> < 0.001).<h4>Conclusions</h4>In patients with T2D and MRF, dapagliflozin reduced the risk of HHF and adverse renal outcomes regardless of baseline characteristics. These analyses support the benefit of dapagliflozin for important outcomes in a broad primary prevention population.

Item Type: Article
Uncontrolled Keywords: Humans, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Benzhydryl Compounds, Glucosides, Treatment Outcome, Primary Prevention, Heart Failure
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 22 Mar 2021 11:44
Last Modified: 18 Jan 2023 22:55
DOI: 10.2337/dc20-2492
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3117987