https://orcid.org/0000-0003-4413-9736
In recent years, improvements in the prognosis of patients with acute myocardial infarction have slowed, with limited new treatment options and a continued high risk of cardiovascular and metabolic events. The dapagliflozin in myocardial infarction (MI) trial was designed to investigate the effect of dapagliflozin 10 mg once daily on a broad range of cardiometabolic outcomes when added to the standard of care in patients hospitalized for myocardial infarction with any degree of impaired left ventricular (LV) systolic function but without known diabetes or chronic symptomatic HF.1 It was conducted as an international registry-based, randomized, double-blind trial2,3 with automated extraction of baseline and follow-up data from two national clinical registries–SWEDEHEART in Sweden and MINAP in the UK.
During 33 months, 4017 patients were randomized to dapagliflozin or placebo. The primary outcome was the hierarchical composite of death, hospitalization for HF, non-fatal MI, atrial fibrillation/flutter, type 2 diabetes mellitus, New York Heart Association Functional Classification at the last visit, and body weight decrease ≥5% at the last visit, analysed with the win ratio analysis method. The key secondary outcome was the same hierarchical composite, excluding the body weight component.
The mean enrolment rate was two patients per site per month.4 The mean age was 62.9 years, and the mean body-mass index was 28.3 kg/m2. Among patients with ST-elevation and non-ST elevation MI, 94.2% and 76.6% underwent primary percutaneous coronary intervention, respectively. The LV ejection fraction was below 50% in the majority of participants (73.2%). Patients were treated with guideline-directed therapies comprising more than 90% use of aspirin, P2Y12 receptor inhibitors, RAAS inhibitors, and statins at randomization.
The analysis of the primary hierarchical composite outcome resulted in significantly more wins for dapagliflozin than for placebo [win ratio, 1.34; 95% confidence interval (CI), 1.20–1.50; P < 0.001] (Figure 1). For the primary win ratio analysis, outcomes were consistent across all pre-specified subgroups, including subgroups based on LV function or median level of troponin elevation. For the key secondary outcome including six of the components, the win ratio was 1.20 (95% CI, 1.04–1.40; P = 0.015). The composite of time to cardiovascular death or hospitalization for HF occurred rarely in both groups: 50/2019 (2.5%) and 52/1998 (2.6%) in patients assigned to dapagliflozin and placebo, respectively, hazard ratio 0.95 (95% CI, 0.64–1.40). The rates of other cardiovascular events were also low, with differences between the groups not reaching nominal statistical significance. No safety concerns were identified.
Wins, ties, and win ratios for primary and key secondary outcomes determined using win ratio analysis. With permission from NEJM Evidence.
In conclusion, in patients with acute MI, after a mean of 1 year of treatment with dapagliflozin, there were significant benefits with regards to cardiometabolic outcomes compared with placebo. The innovative registry-based clinical trial design, incorporating national clinical registry data, facilitated efficient patient recruitment and outcome ascertainment.
Conflict of interest: The DAPA-MI trial was sponsored by Astra Zeneca. S.J. reports institutional research grants/support from AstraZeneca, Novartis, and Amgen. J.O. reports institutional research grants/support from AstraZeneca, Bayer, Novartis, and Roche Diagnostics. R.S. reports institutional research grants/support from AstraZeneca and Cytosorbents, and personal fees from Alfasigma, AstraZeneca, Pfizer, Chiesi, Cytosorbents, Daiichi Sankyo, Idorsia, Novartis, Novo Nordisk PhaseBio, sanofi aventis, and Tabuk.
Data availability
Data are available on request. The data underlying this article will be shared on reasonable request to the corresponding author.
