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Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

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posted on 11.01.2022, 20:10 authored by Avivit Cahn, Stephen D. Wiviott, Ofri Mosenzon, Sabina A. Murphy, Erica L. Goodrich, Ilan Yanuv, Aliza Rozenberg, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John P.H. Wilding, Ingrid A. M. Gause-Nilsson, Anna Maria Langkilde, Marc S. Sabatine, Itamar Raz
Objective: Current guidelines recommend prescribing SGLT-2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c.

Methods: In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population, and with dapagliflozin vs. placebo in HbA1c subgroups were studied by Cox regression models.

Results: In the overall population, increasing HbA1c was associated with higher risk of cardiovascular death or hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) and of the cardiorenal outcome (adjusted HR [95% CI] 1.12 [1.06-1.19], 1.08 [1.04-1.13] and 1.17 [1.11-1.24] per 1% increase respectively). Elevated HbA1c was associated with an increased risk for MACE and for the cardiorenal outcome significantly more in patients with multiple risk factors (MRF), vs. patients with established ASCVD (P-interaction 0.0064 and 0.0093 respectively). Dapagliflozin led to a decrease in the risk of CVD/HHF, HHF and the cardiorenal outcome vs. placebo with no heterogeneity by baseline HbA1c (P-interaction >0.05).

Conclusions: High HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c<7%.

Funding

The sponsor of the DECLARE - TIMI 58 study was initially AstraZeneca and Bristol-Myers Squibb and AstraZeneca later became the sole sponsor of the study. The DECLARE–TIMI 58 trial was a collaboration between the funder and two academic research organizations (TIMI Study Group and Hadassah Medical Organization). The funder was involved in the study design, data collection, data analysis, interpretation, and writing of this report. IAMG-N and AML are employed by the study funder. Data analyses were done by the academic TIMI Study Group, which has access to the complete study database, allowing independent analyses of the results; any discrepancies were resolved by discussion. The DECLARE–TIMI 58 publication committee made the decision to submit for publication.

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