<b>Aims: </b>International
guidelines propose prescribing SGLT-2 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 SGLT-2 inhibitors in MRF patients.
<p><b>Methods: </b>The
DECLARE-TIMI 58 trial randomized 17,160 patients with T2D and MRF (59.4%) or established
ASCVD (40.6%) to dapagliflozin vs. placebo, followed for a median 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. </p>
<p><b>Results:</b>
Among patients with MRF, the reduction with dapagliflozin in risk of
cardiovascular death or hospitalization for heart failure (CVD/HHF; 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 patients
with ASCVD (P<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, HbA1c, weight, systolic blood-pressure and urinary
albumin:creatinine ratio were lower with dapagliflozin vs. placebo and eGFR was
higher (p<0.001). </p>
<p><b>Conclusion:
</b>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
on important outcomes in a broad primary prevention population.</p>
Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58
