After acute myocardial infarction (AMI), the risk of heart failure (HF) and death are elevated. EMPACT-MI (A Study to Test Whether Empagliflozin Can Lower the Risk of Heart Failure and Death in People Who Had a Heart Attack [Myocardial Infarction]) evaluated the efficacy of empagliflozin to reduce cardiovascular risk in patients who remain at HF risk after AMI.

EMPACT-MI was a double-blinded, randomized, placebo-controlled trial which enrolled 6,522 patients hospitalized for AMI with newly reduced left ventricular ejection fraction (<45%) and/or congestion. Randomization was 1:1 to empagliflozin 10 mg daily or placebo, in addition to standard management, within 14 days after admission. The primary endpoint was a composite of hospitalization for HF or all-cause mortality.¹ During a median follow-up of 17.9 months, the primary outcome occurred in 8.2% of the empagliflozin group and 9.1% of the placebo group (p = 0.21). HF hospitalization occurred in 3.6% in the empagliflozin group and 4.7% in the placebo group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.60-0.98). Death from any cause occurred in 5.2% and 5.5%, respectively (HR, 0.96; CI, 0.78-1.19).

Empagliflozin has demonstrated improvement in cardiovascular outcomes in patients with HF, type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD). While EMPACT-MI failed to demonstrate benefit in patients with HF after AMI, the study demonstrated positive effects on HF outcomes. Risk reduction for HF hospitalization was consistent in subgroup sensitivity analyses, including those with and without T2DM. Furthermore, the safety profile was similar to other trials of sodium-glucose cotransportor-2 (SGLT2) inhibitors.

EMPACT-MI adds to a list of negative trials (e.g., DAPA-MI [Dapagliflozin in Patients With Myocardial Infarction] and PARADISE-MI [Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after MI]) for patients post-AMI at HF risk.^2,3 Low event rates may be attributed to timely revascularization and post-AMI care. In EMPACT-MI, 90% received revascularization, 98% received antiplatelets, and 90% received statins. Limitations include: 1) end-point events were not centrally adjudicated; 2) outpatient HF events were not analyzed as clinical endpoints; and 3) there was a low representation of women, older adults, and ethnic minorities. Additional studies are needed to determine optimal timing and patient selection for SGLT2 inhibitor therapy post-AMI. Given the results of EMPACT-MI, traditionally proven therapies, such as renin-angiotensin-aldosterone system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists, should be initiated first for patients with AMI and newly reduced ejection fraction. SGLT2 inhibitor use can be delayed and re-evaluated as an outpatient or initiated inpatient only for patients who have other indications, such as diabetes mellitus or CKD.

References

1. Butler J, Jones WS, Udell JA, et al. Empagliflozin after acute myocardial infarction. N Engl J Med 2024;390:1455-66.
2. James S, Erlinge D, Storey RF, et al. Dapagliflozin in myocardial infarction without diabetes or heart failure. NEJM Evid 2024;3:EVIDoa2300286.
3. Pfeffer MA, Claggett B, Lewis EF, et al. Angiotensin receptor-neprilysin inhibition in acute myocardial infarction. N Engl J Med 2021;385:1845-55.