Study to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction - EMPACT-MI

Apr 06, 2024
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Anthony A. Bavry, MD, MPH, FACC
Trial Sponsor:
Boehringer Ingelheim and Eli Lilly
Date Presented:
04/06/2024
Date Published:
04/06/2024
Original Posted Date:
04/06/2024
References

Contribution To Literature:

The EMPACT-MI trial showed that in patients with AMI at increased risk of HF, empagliflozin did not reduce the composite risk of all-cause mortality and HF hospitalization compared with placebo. However, empagliflozin may be associated with fewer first and total HF hospitalizations across the spectrum of LVEF and congestion risk profiles.

Description:

The goal of the trial was to determine whether adding the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin to the treatment of acute myocardial infarction (AMI) affects future mortality or heart failure (HF) in at-risk patients.

Study Design

  • Randomized
  • Double-blind
  • International

Patients with AMI and at high risk of developing acute HF were randomized in a 1:1 fashion to receive empagliflozin 10 mg daily (n = 3,260) or matching placebo (n = 3,262) within 14 days of hospital admission.

  • Total number of enrollees: 6,522
  • Median follow-up: 17.9 months
  • Mean patient age: 64 years
  • Percentage female: 25%

Inclusion criteria:

  • Age ≥18 years
  • ST-segment elevation MI (STEMI) or non-STEMI (NSTEMI) due to acute coronary artery pathology
  • High risk of HF, defined as: 1) signs (e.g., rales, elevated jugular venous pressure) or symptoms (e.g., dyspnea, fatigue) of congestion requiring medical treatment, or 2) newly depressed left ventricular ejection fraction (LVEF) <45%
  • ≥1 additional HF risk factor: age >65 years, new LVEF <35%, prior MI, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, atrial fibrillation, type 2 diabetes mellitus (DM), elevated B-type natriuretic peptide (BNP) or NT-proBNP, uric acid >7.5 mg/dL, pulmonary artery systolic pressure >40 mm Hg, no revascularization, three-vessel coronary artery disease, peripheral artery disease

Exclusion criteria:

  • Chronic HF preceding index MI
  • Systolic blood pressure <90 mm Hg
  • Cardiogenic shock <24 hours prior to randomization
  • Planned coronary artery bypass grafting
  • Severe valvular heart disease
  • eGFR <20 mL/min/1.73 m2 or dialysis requirement
  • Type 1 DM

Other salient features/characteristics:

  • LVEF <45% alone: 41%
  • Congestion alone: 23%
  • LVEF <45% and congestion: 33%
  • Age ≥65 years: 50%

Principal Findings:

The primary outcome, composite of HF hospitalization or all-cause death, for empagliflozin vs. placebo, was: 5.9 vs. 6.6 events per 100 patient-years, hazard ratio (HR) 0.90 (95% confidence interval [CI] 0.76-1.06), p = 0.21.

Secondary outcomes for empagliflozin vs. placebo:

  • All-cause death: 5.2% vs. 5.5%, HR 0.96 (95% CI 0.78-1.19)
  • First HF hospitalization: 2.6 vs. 3.4 events per 100 patient-years, HR 0.77 (95% CI 0.60-0.98), p = 0.031
  • Treatment effect for first HF hospitalization consistent across LVEF (pinteraction = 0.95), presence of congestion (pinteraction = 0.88), and combination of LVEF and congestion (ptrend = 0.42)
  • Total HF hospitalization: 2.4 vs. 3.6 adjusted events per 100 patient-years, incident rate ratio 0.67 (95% CI 0.51-0.89), p = 0.006
  • Treatment effect for total HF hospitalization consistent across LVEF (pinteraction = 0.90), presence of congestion (pinteraction = 0.89), and combination of LVEF and congestion (ptrend = 0.42)

Safety outcomes for empagliflozin vs. placebo, events per 100 patient-years:

  • Adverse event necessitating drug discontinuation: 2.0 vs. 3.0
  • Hypotension: 0.8 vs. 0.9
  • Acute kidney injury: 0.7 vs. 1.1

Interpretation:

In EMPACT-MI, early initiation of empagliflozin following AMI did not reduce the combined incidence of all-cause death and first HF hospitalization. However, secondary analyses demonstrated a potential reduction in both first and total HF hospitalizations associated with empagliflozin. This is in contrast to DAPA-MI, in which the primary hierarchical endpoint favored dapagliflozin largely because of improved cardiometabolic and not HF outcomes. The current study population was notably enriched for patients at high risk of incipient HF, which may account for the higher event rate and consequent treatment effect. These results were consistent not only across relevant subgroups, such as STEMI versus NSTEMI and diabetes status, but also across a range of LVEF and congestion profiles observed. Although prespecified, these secondary outcomes remain exploratory, as the primary endpoint was not reached. The current data nevertheless suggest a potential role for the early use of SGLT2 inhibitors to improve HF outcomes following AMI in select, high-risk patients.

References:

Butler J, Jones WS, Udell JA, et al. Empagliflozin After Acute Myocardial Infarction. N Engl J Med 2024;390:1455-66.

Udell JA, Petrie MC, Jones WS, et al. Left Ventricular Function, Congestion, and Effect of Empagliflozin on Heart Failure Risk After Myocardial Infarction. J Am Coll Cardiol 2024;Apr 6:[Epub ahead of print].

Hernandez AF, Udell JA, Jones WS, et al. Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial. Circulation 2024;Apr 6:[Epub ahead of print].

Presented by Dr. Javed Butler at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 6, 2024.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Acute Coronary Syndromes

Keywords: ACC24, ACC Annual Scientific Session, Heart Failure, Myocardial Infarction, Novel Agents, Sodium-Glucose Transporter 2 Inhibitors


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