Dapagliflozin improves cardiometabolic outcomes in myocardial infarction  

Dapagliflozin reduced a win ratio outcome of cardiometabolic disease in patients with acute myocardial infarction (MI) and impaired left ventricular (LV) systolic function who did not have diabetes or chronic heart failure (HF). No differences were seen in cardiovascular outcomes. 

“Since SGLT2 inhibitors have positive effects on almost all cardiometabolic parameters, dapagliflozin could be an effective secondary prevention medication for patients who have had an MI,” argued Prof. Stefan James (Uppsala University, Sweden) [1]. The registry-based, double-blind, randomised, phase 3 DAPA-MI trial (NCT04564742) aimed to test the effect of dapagliflozin on cardiometabolic and cardiovascular outcomes in patients with acute MI but without diabetes or chronic HF [2]. Patients who had had a non-STEMI or STEMI in the last 10 days were eligible for enrollment in the trial.

The 4,017 participants were randomised 1:1 to the SGLT2 inhibitor dapagliflozin (10 mg once daily) or placebo. The composite of cardiovascular death and hospitalisation for HF was the initial primary outcome. “It became evident that the number of primary composite outcome events was much lower than expected,” expressed Prof. James [1]. “Therefore, the primary endpoint was changed.” The novel primary endpoint was a hierarchical composite outcome (win ratio) of death, hospitalisation for HF, non-fatal MI, atrial fibrillation, new diagnosis of type 2 diabetes, NYHA functional class status, and body weight decrease of at least 5%. “Importantly, this study population was very well treated according to guideline recommendations,” emphasised Prof. James.

The primary outcome showed a win ratio of 1.34 in favour of participants in the dapagliflozin arm (95% CI 1.20–1.50; P<0.001). The corresponding win percentages were 32.9% in favour of dapagliflozin, 24.6% in favour of placebo, and 42.5% ties. “When we look more closely at the components of the primary outcome, we can see that the effect is driven by cardiometabolic outcomes, such as diabetes diagnosis and body weight reduction, rather than cardiovascular outcomes,” added Prof. James.

In conclusion, dapagliflozin, on top of guideline-directed medical therapy, offered benefits for patients with acute MI and impaired LV systolic function who did not have diabetes or chronic HF. “The current trial was underpowered to evaluate hard cardiovascular endpoints,” said Prof. Stephen Wiviott (Brigham and Women’s Hospital, MA, USA). “From my standpoint, DAPA-MI does not suggest a new mandate to expand SGLT2 inhibitor use to an isolated MI population without other SGLT2 inhibitor indications but does support the safety of use among patients with acute coronary syndromes.

1. 
   
   1. James S, et al. Dapagliflozin in myocardial infarction without diabetes or heart failure. LB02, AHA Scientific Sessions 2023, 11–13 November, Philadelphia, USA.
   2. James S, et al. NEJM Evid. 2023; Nov 11. DOI: 10.1056/EVIDoa2300286.

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Posted on 29 January, 202422 February, 2024