NEW ORLEANS — Patients with type 2 diabetes mellitus (T2DM) and a prior history of myocardial infarction (MI) have a high risk of major adverse cardiovascular events (MACE), cardiovascular mortality, and hospitalization for heart failure (HHF). Treatment with dapagliflozin in these patients can reduce the risk of these cardiovascular (CV) outcomes, according to a sub-analysis from the DECLARE TIMI-58 Trial presented by researchers at the 2019 American College of Cardiology annual meeting held in New Orleans, March 16-18.
A multi-international team of researchers examined the outcomes of T2DM patients with atherosclerotic cardiovascular disease (ASCVD; n=6974) or multiple CV risk factors (n=10,186) who were randomized to either once-daily 10 mg dapagliflozin or matching placebo.
Patients with established ASCVD were ≥40 years of age and had a history of heart disease, cerebrovascular disease, or peripheral arterial disease. Patients with prior MI (n=3584) were considered a pre-specified subgroup of interest. A composite of MACE (CV death, MI, or ischemic stroke) and a composite of CV death or HHF were included in the analysis as the 2 primary endpoints.
Treatment with once-daily dapagliflozin at 10 mg per day vs placebo was associated with a significant reduction in the relative risk of MACE of 16% as well as a reduction in absolute risk of 2.6% in patients with a prior MI (15.2% vs 17.8%, respectively; hazard ratio [HR], 0.84; 95% CI, 0.72-0.99; P =.039).
There was no observable treatment effect relative to placebo in patients without a history of MI on MACE (7.1% vs 7.1%, respectively; HR, 1.00; 95% CI, 0.88- 1.13; P =.97).
A greater benefit was found when patients were treated with dapagliflozin within 2 years following the last acute event (P interaction trend =.007). In patients with a prior MI, the relative risk reductions in CV death/HHF were significant at 1.9% (8.6% vs. 10.5%; HR, 0.81 95% CI 0.65-1.00, P =.046) and 0.6% (3.9% vs 4.5%; HR, 0.85; 95% CI, 0.72-1.00; P =.055) in patients without a prior MI (P interaction for relative difference, 0.69; for absolute risk difference, 0.010).
The researchers stated that the sub-analysis “was not powered to detect all possible event reductions and treatment-by-subgroup interactions,” which represents a limitation of the trial.
According to the researchers, additional “studies should aim to confirm the large clinical benefits with sodium glucose transporter-2 inhibitors that we observed in patients with prior MI.”
Furtado RHM, Bonaca MP, Raz I, et al. Dapagliflozin and cardiovascular outcomes in patients with type 2 diabetes and prior myocardial infarction: A sub-analysis from DECLARE TIMI-58 Trial. Presented at: the 2019 American College of Cardiology annual meeting; March 16-18, 2019; New Orleans, LA.