In acute MI, dapagliflozin confers cardiometabolic benefit, in absence of diabetes, HF
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Key takeaways:
- Dapagliflozin was superior vs. placebo in reducing cardiometabolic outcomes in patients with MI and impaired LV function without HF or diabetes.
- Body weight was also improved with dapagliflozin.
PHILADELPHIA — In patients without diabetes or heart failure presenting with acute MI and impaired left ventricular function, dapagliflozin improved cardiometabolic outcomes compared with placebo, according to the DAPA-MI trial.
There was no impact of treatment once-daily dapagliflozin (Farxiga, AstraZeneca) on a composite outcome of CV death or hospitalization for HF compared with placebo.
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Results of the multicenter, parallel-group, registry-based, randomized, phase 3 DAPA-MI trial were presented at the American Heart Association Scientific Sessions and simultaneously published in NEJM Evidence.
“The outcomes of patients with myocardial infarction have improved considerably. However, that improvement has come to a plateau and with still continuous high risk of cardiovascular and metabolic negative events,” Stefan James, MD, PhD, professor of cardiology at Uppsala University, scientific director of Uppsala Clinical Research Center and senior interventional cardiologist at Uppsala University Hospital, Sweden, said during a presentation. “When we designed the [DAPA-MI] trial, we listed ... what we thought might be the ideal achievements with a secondary prevention medication.”
These achievements included reducing recurrent MI, HF and mortality as well as improving BP, kidney function, glucose levels, body weight, lipid profile, exercise capacity and smoking cessation, he said.
“We realized that, in fact, SGLT2 inhibition has shown positive effects of almost all of these cardiometabolic parameters. So, it may be a very effective secondary prevention medication,” James said.
Using already existing national clinical registries in Sweden and the U.K., James and colleagues enrolled 4,017 patients (mean age, 63 years) without known diabetes or HF who presented with MI and impaired LV function or Q-waves to assess whether once-daily dapagliflozin 10 mg, on top of standard of care, was superior compared with placebo.
The primary outcome of interest was a composite of death, HF hospitalization, nonfatal MI, atrial fibrillation/atrial flutter, new-onset type 2 diabetes, HF symptoms as measured by NYHA classification and body weight decrease of 5% or more at last visit. Secondary outcomes of interest included all components of the primary outcome, with the exception of reduced body weight.
At baseline, 65% of participants had STEMI, 8% had prior MI and 2% had prior stroke.
More than 80% of participants were receiving guideline-directed medical therapies including ACE inhibitors, statins, beta-blockers and dual antiplatelet therapy.
LV ejection fraction was less than 50% for 66% of the cohort.
James reported that dapagliflozin, on top of standard care, was superior compared with placebo for the primary outcome, with a win ratio of 1.34 (95% CI, 1.2-1.5; P < .001).
Dapagliflozin was also superior compared with placebo for the composite secondary outcome, with a win ratio of 1.2 (95% CI, 1.04-1.4; P = .015), according to the results.
The benefits of dapagliflozin in patients with MI and impaired LV function or Q-waves without HF or diabetes was consistent across all prespecified subgroups, including those grouped by age, country, sex, BMI, BP and baseline LVEF, blood glucose and creatinine.
James reported no unexpected safety concerns during the trial, with similarly low rates of serious adverse events leading to death in both groups (1.5%).
The researchers reported a lower rate of new diagnosis of type 2 diabetes and a significant reduction in body weight among patients who received dapagliflozin compared with placebo (1.65 kg; 95% CI, 2.12 to 1.18).
“In patients with acute MI and impaired LV function without prior diabetes or heart failure, dapagliflozin demonstrated significant benefit with regard to improvements in cardiometabolic outcomes as compared to placebo,” James said during the presentation. “The cardiometabolic benefit was consistent across all prespecified subgroups, and there were no safety concerns. Clinical event rates were low, with no significant difference between the randomized groups. Importantly, innovative registry-based clinical trial design incorporating national clinical registry data facilitated efficient patient enrollment and outcome ascertainment.”
Reference:
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James SK, et al. LBS.02. Hot topics in management of coronary artery disease/acute coronary syndrome. Presented at: American Heart Association Scientific Sessions; Nov. 11-13, 2023; Philadelphia.
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