Dapagliflozin in myocardial infarction without diabetes or heart failure

Presented at the AHA Scientific Sessions 2023 by: Stefan James, MD, PhD - Uppsala, Sweden

Introduction and methods

There is a need to improve the management of patients who experienced a myocardial infarction (MI) to prevent the risk of future CV and metabolic events. SGLT2 inhibitors have beneficial effects on the risk of diabetes and CVD, HF irrespective of LVEF, and CKD. They improve various cardiometabolic parameters, and therefore may be an effective secondary prevention medication after an MI. The aim of the DAPA-MI trial was to investigate whether dapagliflozin has beneficial effects on cardiometabolic outcomes in patients with acute MI without diabetes or chronic HF.

DAPI-MI was a multicenter, registry-based, randomized, double-blind, placebo-controlled trial in which 4017 patients with MI (NSTEMI or STEMI) within 10 days from index MI with impaired LV systolic function were enrolled. Patients from two large national registries were included in the DAPA-MI database: (1) from the SWEDEHEART registry, which included data of 39 centers in Sweden; and (2) from the MINAP registry, which included data of 64 centers in the UK. All baseline characteristics, medications and follow-up data were extracted from these registries. Patients were randomized to dapagliflozin 10 mg once daily (n=2019) or placebo (n=1998) on top of standard of care. Main exclusion criteria were: T1D or T2D; chronic HF with a prior hospitalization for HF within the last year and LVEF ≤40%; and eGFR <20 mL/min/1.73 m². The median follow-up period was 11.6 months.

The primary endpoint was a hierarchical (win ratio) composite endpoint comprised of 7 components, namely death, hospitalization for HF, non-fatal MI, AF/flutter event, new diagnosis of T2D, NYHA functional class at last visit, and body weight decrease at least 5% at last visit. The key secondary outcome was the primary endpoint excluding body weight decreases, the other secondary endpoint was time to first occurrence of hospitalization for HF or CV death.

Main results

• Dapagliflozin had more wins on the primary hierarchical composite endpoint compared with placebo (32.9% wins for dapagliflozin vs. 24.6% wins for placebo; win ratio: 1.34; 95%CI: 1.20-1.50; P<0.001).
• Dapagliflozin had more wins on the key secondary endpoint compared with placebo (20.3% wins for dapagliflozin vs. 16.9% wins for placebo; win ratio: 1.20; 95%CI: 1.04-1.40; P<0.015).
• The beneficial effect of dapagliflozin on the primary composite endpoint was consistent in various prespecified subgroups, independent of BMI, kidney function, BP, and baseline HbA1c.
• The composite of time to CV death or hospitalization for HF occurred in 2.5% of patients in the dapagliflozin group compared with 2.6% of patients in the placebo group (HR: 0.95; 95%CI: 0.64-1.40)
• There was a lower incidence of new diagnosis of T2D in the dapagliflozin group compared with the placebo group (2.1% vs. 3.9%, respectively; HR: 0.53; 95%CI: 0.36-0.77).
• Dapagliflozin lowered body weight compared with placebo (-1.65 kg; 95%CI: -2.12 to -1.18).
• There were no unexpected safety concerns reported. Serious adverse events leading to death occurred to a similar extent in both treatment groups (incidence of 1.5% in both groups).

Conclusion

The DAPA-MI trial showed that dapagliflozin improves cardiometabolic outcomes in patients with acute MI and impaired LV systolic function without diabetes or chronic HF compared with placebo. The benefit of dapagliflozin on cardiometabolic outcomes was consistent across various pre-specified subgroups, and no new safety concerns were reported. “The innovative registry-based clinical trial design, incorporating national clinical registry data, facilitated efficient patient recruitment and outcome ascertainment.”, concluded Stefan James.

- Our reporting is based on the information provided at the AHA Scientific Session 2023 -

The results of this study were simultaneously published in NEJM Evidence