Dapagliflozin and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Prior Myocardial Infarction: A Sub-analysis From DECLARE TIMI-58 Trial.
Circulation. 2019 Mar 18;:
Authors: Furtado RHM, Bonaca MP, Raz I, Zelniker TA, Mosenzon O, Cahn A, Kuder J, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Nicolau JC, Gause-Nilsson IAM, Fredriksson M, Langkilde AM, Sabatine MS, Wiviott SD
BACKGROUND: Sodium glucose transporter-2 inhibitors (SGLT2i) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM) and a history of atherosclerotic cardiovascular (CV) disease (ASCVD). Because of their baseline risk, patients with prior myocardial infarction (MI) may derive even greater benefit from SGLT2i therapy.
METHODS: DECLARE TIMI-58 randomized 17,160 patients with T2DM and either established ASCVD (n = 6,974) or multiple risk factors (MRF) (n = 10,186) to dapagliflozin versus placebo. The two primary endpoints were composite of MACE (CV death, MI or ischemic stroke) and the composite of CV death or hospitalization for heart failure (HHF). Prior MI (n = 3,584) was a pre-specified subgroup of interest.
RESULTS: In patients with prior MI (n=3,584), dapagliflozin reduced the relative risk of MACE by 16% and the absolute risk by 2.6 % (15.2% vs. 17.8%; HR 0.84; 95%CI 0.72-0.99; p=0.039) whereas there was no effect in patients without prior MI (7.1% vs. 7.1%; HR 1.00, 95%CI 0.88-1.13; p=0.97) (p-interaction for relative difference 0.11 and for absolute risk difference 0.048), including in patients with established ASCVD but no history of MI (12.6 % versus 12.8%, HR 0.98; 95% CI 0.81-1.19). There seemed to be a greater benefit for MACE within 2 years after last acute event (p-interaction trend = 0.007). The relative risk reductions in CV death/HHF were more similar, but the absolute risk reductions tended to be greater: 1.9 % (8.6% vs. 10.5%; HR 0.81 95% CI 0.65-1.00, P=0.046) and 0.6% (3.9% vs. 4.5%; HR 0.85; 95% CI 0.72-1.00; P=0.055) in patients with and without prior MI, respectively (p-interaction for relative difference 0.69 and for absolute risk difference 0.010).
CONCLUSIONS: Patients with T2DM and prior MI are at high risk of MACE and CV death/HHF. Dapagliflozin appears to robustly reduce the risk of both composite outcomes in these patients. Future studies should aim to confirm the large clinical benefits with SGLT2i we observed in patients with prior MI.
CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT01730534.
PMID: 30882239 [PubMed - as supplied by publisher]