Farxiga reduced major adverse cardiovascular events by 16% in patients who had a prior heart attack

Farxiga reduced hospitalisation for heart failure regardless of ejection fraction status

Positive results from a pre-specified sub-analysis of the Phase III DECLARE-TIMI 58 trial showed that Farxiga (dapagliflozin) reduced the relative risk of major adverse cardiovascular events (MACE) by 16% compared to placebo in patients with type-2 diabetes (T2D) who had a prior heart attack (myocardial infarction).

In another pre-specified sub-analysis, Farxiga compared to placebo reduced the relative risk of hospitalisation for heart failure (hHF) in patients with T2D regardless of their ejection fraction (EF) status, a measurement of the percentage of blood leaving the heart with each contraction.

The data were presented today at the American College of Cardiology’s (ACC) 68th Annual Scientific Session, New Orleans, USA and were published in Circulation.1,2

Elisabeth Björk, Senior Vice President, Head of late Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, said: “These data build upon the existing evidence of the cardio-renal effects of Farxiga, with important new evidence on heart failure and MACE. Heart failure is one of the most common early cardiovascular complications of type-2 diabetes. Despite advances in healthcare, it remains as life-threatening and prevalent as the combined incidence of the top-four most common forms of cancer.Therefore, more needs to be done for patients.” 

Dr. Stephen Wiviott of Brigham and Women’s Hospital and Harvard Medical School, a senior investigator with the Thrombolysis in Myocardial Infarction (TIMI) study group and co-principal investigator of the trial, said: “Data from these pre-specified sub-analyses offer important and clinically-relevant insights for cardiologists and their patients. We now have new evidence from DECLARE-TIMI 58 that shows Farxiga consistently reduced hospitalisation for heart failure across a broad range of patients with type-2 diabetes, regardless of their history of existing CV disease, including heart attack, or heart failure.”

These pre-specified sub-analyses of DECLARE-TIMI 58 add to the positive primary results of the trial presented in November 2018, which showed that Farxiga significantly reduced the risk of the composite of hHF or CV death compared to placebo, consistently across the trial’s entire patient population. Additionally, there were fewer major adverse cardiovascular events observed with Farxiga in the broad patient population, however this did not reach statistical significance.

Farxiga is a selective inhibitor of human sodium-glucose co-transporter 2 (SGLT2 inhibitor) indicated as monotherapy and as part of combination therapy to improve glycaemic control in adult patients with T2D. Farxiga is not indicated to reduce the risk of CV events, heart failure or death.

Press release Astra Zeneca AB

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https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.119.039996

Dapagliflozin and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Prior Myocardial Infarction: A Sub-analysis From DECLARE TIMI-58 Trial

Remo H. M. Furtado et al

Originally published18 Mar 2019 https://doi.org/10.1161/CIRCULATIONAHA.119.039996

Abstract

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.

 

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