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Stratifying the effects of SGLT2i

Two prespecified analyses of the DECLARE–TIMI 58 trial, presented at ACC.19, show that in patients with type 2 diabetes mellitus (T2DM), the sodium–glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin has greater cardiovascular benefit in those with heart failure with reduced ejection fraction (HFrEF) at baseline and in those with prior myocardial infarction (MI).

Of the 17,160 patients with T2DM in the trial, 3.9% had HFrEF (ejection fraction (EF) <45%), 7.7% had heart failure (HF) without known reduced EF and 88.4% had no history of HF. Compared with placebo, dapagliflozin reduced the risk of cardiovascular death and hospitalization for HF to a greater extent in patients with HFrEF (HR 0.62, 95% CI 0.45–0.86) than in patients without HFrEF (HR 0.88, 95% CI 0.76–1.02, P = 0.046 for interaction). This difference was driven by a strong reduction in cardiovascular death and all-cause death in patients with HFrEF but not in those without HFrEF. Among patients without HFrEF, the effect of dapagliflozin was similar in patients with HF without known reduced EF and in patients without a history of HF.

Patients with prior MI (20.9%) treated with dapagliflozin had a 16% reduction in the relative risk and a 2.6% reduction in the absolute risk of major adverse cardiovascular events (MACE) compared with the placebo group (15.2% versus 17.8%; HR 0.84, 95% CI 0.72–0.99, P = 0.039), mainly driven by reductions in the rate of recurrent MI. By contrast, dapagliflozin had no effect on the risk of MACE in patients without a history of MI (7.1% versus 7.1%). The relative risk reduction in cardiovascular death and hospitalization for HF with dapagliflozin was similar in patients with or without prior MI, but the absolute risk reduction tended to be greater in patients with prior MI. “Whether this benefit could be expanded to the acute phase of MI or to patients with prior MI even if they do not have T2DM should be addressed in future studies,” note the researchers.


Original articles

  1. Kato, E. T. et al. Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus. Circulation (2019)

    Article  PubMed  Google Scholar 

  2. Furtado, R. H. M. et al. Dapagliflozin and cardiovascular outcomes in patients with type 2 diabetes and prior myocardial infarction: a sub-analysis from DECLARE TIMI-58 trial. Circulation (2019)

    Article  PubMed  Google Scholar 

Further reading

  1. Nassif, M. & Kosiborod, M. Effect of glucose-lowering therapies on heart failure. Nat. Rev. Cardiol. 15, 282–291 (2018)

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Irene Fernández-Ruiz.

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Fernández-Ruiz, I. Stratifying the effects of SGLT2i. Nat Rev Cardiol 16, 322 (2019).

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