Key Points:
- Incident heart failure remains common among patients who experience acute myocardial infarction despite recent advances in medical therapy and revascularization strategies.
- The EMPACT MI trial randomized 6,522 participants with acute myocardial infarction (STEMI or NSTEMI) at high risk of heart failure to empagliflozin 10mg daily or placebo.
- Over a median follow-up of 17.9 months, the primary endpoint of time to first heart failure hospitalization or all-cause mortality was not significantly reduced with empagliflozin.
Patients who experience an acute myocardial infarction are at high-risk for developing heart failure despite recent advances in medical therapy and revascularization approaches. Sodium/glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce the risk of heart failure events among individuals with established heart failure and those at risk for incident heart failure. However, data regarding their efficacy for reducing heart failure events in the setting of an acute myocardial infarction have been lacking.
The EMPACT-MI trial, was a global, randomized, placebo-controlled trial, which enrolled 6,522 participants from 22 countries and evaluated the effect of empagliflozin on a primary endpoint of time to first heart failure hospitalization or all-cause mortality among individuals with acute myocardial infarction at high risk of heart failure as compared to placebo. The trial enrolled individuals with spontaneous acute STEMI or NSTEMI within 14 days of hospital admission. Participants must have been deemed at high-risk for heart failure defined as either signs or symptoms of congestion requiring treatment or newly developed left ventricular ejection fraction of less than 45%. Furthermore, participants required at least one additional heart failure risk factor. Notable exclusions included individuals with chronic heart failure, systolic blood pressure < 90 mmHg at the time of randomization, cardiogenic shock or use of intravenous inotropes within 24 hours of randomization, current or planned treatment with an SGLT2i, any severe valvular heart disease, end-stage renal disease (eGFR < 20 ml/min/1.73 m2), and type 1 diabetes mellitus. A novel aspect of the study was the use of blinded investigator review instead of central adjudication.
The mean age of the participants was 64 years and 25% were women. Approximately 75% were enrolled with an index STEMI event and 78% had a left ventricular ejection fraction of less than 45%. A high proportion of participants underwent revascularization for their index MI (89%) and were discharged on renin-angiotensin modulators (82.5%) and a beta blocker (86.7%). Over a median follow-up of 17.9 months, the primary endpoint occurred among 8.2% participants in the empagliflozin group and among 9.1% of individuals in the placebo arm (hazard ratio, 0.90; 95% CI: 0.76 to 1.06; p=0.21). Examining the components of the primary endpoint individually, empagliflozin did not reduce time to all-cause mortality, however, it demonstrated a 23% reduction in time to first heart failure hospitalization as compared to placebo (3.6% versus 4.7%, respectively: hazard ratio 0.77; 95% CI: 0.60 to 0.98). Additionally, in an exploratory analysis, empagliflozin demonstrated a 33% relative reduction in the total number of heart failure hospitalizations as compared to placebo (event relative risk 0.67; 95% CI: 0.51 to 0.89). There was no significant difference in serious adverse events among the two groups.
In conclusion, empagliflozin did not reduce the risk of a composite primary endpoint of time to first heart failure hospitalization or all-cause mortality among acute spontaneous myocardial infarction patients who were at high-risk for heart failure. However, empagliflozin reduced the risk of heart failure. The magnitude of benefit observed was similar to that in previous trials involving SGLT2 inhibitors.