EMPACT-MI: Empagliflozin Falls Short on Primary Endpoint After Acute Heart Attack

A 6,522-patient randomised trial found empagliflozin did not significantly reduce the composite of heart failure hospitalization or all-cause death after acute MI (8.2% vs. 9.1%; P=0.21). Secondary analyses showed reductions in heart failure hospitalizations specifically, but do not change the primary result.

Empagliflozin (Jardiance®), an SGLT-2 inhibitor, did not significantly reduce the primary composite endpoint of heart failure (HF) hospitalization or all-cause mortality when started within 14 days of an acute myocardial infarction (MI), according to the EMPACT-MI trial published April 2024 in the New England Journal of Medicine.

Primary endpoint — not met: Among 6,522 patients randomised to empagliflozin (n=3,260) or placebo (n=3,262), a first HF hospitalization or death from any cause occurred in 8.2% of the empagliflozin group versus 9.1% in the placebo group (hazard ratio 0.90; 95% CI 0.76–1.06; P=0.21). This difference was not statistically significant.

Trial design: EMPACT-MI (NCT04509674) enrolled patients hospitalised for STEMI or NSTEMI at elevated risk for heart failure, defined as newly reduced left ventricular ejection fraction (LVEF <45%) or signs/symptoms of congestion requiring treatment, plus at least one additional high-risk feature (age >65, prior MI, eGFR <60, atrial fibrillation, type 2 diabetes, or elevated natriuretic peptides). Randomisation occurred within 14 days. Median follow-up was 17.9 months.

Secondary HF analyses (prespecified, from Circulation): A prespecified secondary analysis published simultaneously in Circulation (DOI 10.1161/CIRCULATIONAHA.124.069217) found that empagliflozin was associated with a significant reduction in first HF hospitalization alone (3.6% vs 4.7%; HR 0.77; 95% CI 0.60–0.98; P=0.031) — approximately 23% relative reduction — and in total HF hospitalizations (148 vs 207 events; rate ratio 0.67; 95% CI 0.51–0.89; P=0.006) — approximately 33% relative reduction.

Critical framing: These secondary findings are hypothesis-generating and do not override the primary result. Patients should not interpret these results as establishing empagliflozin as indicated post-MI; regulatory determination of that question requires further review.

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Primary endpoint not met: first HF hospitalization or all-cause death occurred in 8.2% of the empagliflozin group vs 9.1% of the placebo group (HR 0.90; 95% CI 0.76–1.06; P=0.21).

journal paper Empagliflozin after Acute Myocardial Infarction — NEJM (April 2024) 10.1056/NEJMoa2314051

6,522 patients randomised (3,260 empagliflozin, 3,262 placebo); sponsors Boehringer Ingelheim and Eli Lilly; primary completion November 5, 2023.

journal paper Empagliflozin after Acute Myocardial Infarction — NEJM (April 2024) 10.1056/NEJMoa2314051

Prespecified secondary analysis (Circulation): empagliflozin reduced first HF hospitalization 3.6% vs 4.7% (HR 0.77; 95% CI 0.60–0.98; P=0.031) — approximately 23% relative reduction.

journal paper Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial — Circulation 10.1161/CIRCULATIONAHA.124.069217

Total HF hospitalizations: 148 vs 207 events (rate ratio 0.67; 95% CI 0.51–0.89; P=0.006) — approximately 33% relative reduction.

journal paper Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial — Circulation 10.1161/CIRCULATIONAHA.124.069217

After publication, a separate AI panel re-verifies every edition against these same sources. The running claim-confirmation rate and every correction are public on the accuracy ledger.

Trials Today

Phase 3 OCEANIC-AF / asundexian vs apixaban in atrial fibrillation — 14,830 patients; terminated November 2023 for inferior efficacy — asundexian arm had significantly more strokes (1.3% vs 0.4%); results published NEJM September 2024.

Phase 3 EMPACT-MI / empagliflozin after acute myocardial infarction — 6,522 patients; primary composite endpoint (HHF or all-cause death) not met — 8.2% vs 9.1%, P=0.21. Results published NEJM April 2024.