EMPACT-MI: Is Preventing HF After Heart Attack the Next Frontier for SGLT2 Inhibitors?

Since winning FDA approval a decade ago to treat type 2 diabetes (T2D), the sodium glucose co-transporter 2 (SGLT2) inhibitor class has demonstrated benefits in reducing heart failure hospitalization and in offering renal protection. More recent evidence has shown that those hospitalized for heart failure benefit if the drugs are prescribed before patients are discharged.

So, what’s next?

Forthcoming studies will answer a question suggested in 2015, when the landmark EMPA-REG OUTCOME study found that empagliflozin (Jardiance, Boehringer Ingelheim and Eli Lilly) cut the risk of death from cardiovascular causes—including heart attack or stroke—by 38%. The idea that a glucose-lowering therapy could prevent heart attacks was stunning, and it raised questions being answered now: can empagliflozin prevent heart failure in patients who have already had myocardial infarction (MI)? And is it safe?

Butler

To find out, investigators designed the EMPACT-MI trial, which is scheduled to conclude at the end of this month, according to clinicaltrials.gov.

Javed Butler, MD, MPH, MBA, of the University of Mississippi and Baylor, Scott, and White Research Institute in Dallas, Texas, presented baseline characteristics of the trial's patient enrollment during a short presentation Friday at the European Society of Cardiology 2023 Congress, being held in Amsterdam.

“So, we know that patients post-MI are at a higher risk of mortality from recurrent ischemic events and for developing heart failure,” Butler told the group gathered in the research hall.

“It’s been about 2 decades since we had the last positive trial in patients with post-MI showing a risk reduction in new onset of heart failure,” he continued, explaining that SGLT2 inhibitors have been shown to reduce the risk of developing new onset of heart failure in various populations like diabetes and CKD, as well as improve outcomes for a broad spectrum of heart failure.

“But we don’t have any data in patients with MI—and that was the idea behind this trial.”

He outlined the requirements for the trial, which has randomized 6522 patients to 10 mg of empagliflozin or placebo in addition to standard of care. Patients were eligible for the study if they had no history of heart failure, if they had been hospitalized for an acute MI and had signs or symptoms of congestion that required treatment and/or a newly depressed left ventricle ejection fraction (LVEF) below 45%.

Following enrollment, Butler said, “The baseline characteristics of these patients are pretty comparable to what we see in the recent post-MI patient population.”

Patients were also required to have at least 1 additional enrichment criterion; these factors included being at least 65 years old, or having type 2 diabetes, atrial fibrillation, 3-vessel coronary artery disease, LVEF below 35%, elevated uric acid, pulmonary artery systolic pressure > 40 mm Hg, or reduced kidney function. Among the enrolled patients, “About 70% had more than one criteria,” Butler said, “the most common one being age older than 65.”

Although Butler explained the trial was open to patients who had been hospitalized within 14 days for an MI, most who enrolled were within 5 days of an MI.

The median age of the trial population is 64 years of age (interquartile range, 56-71) and 75.1% are male. Key comorbidities are: hypertension, 69.1%; T2D, 31.7%; prior MI, 13.0%; atrial fibrillation, 10.9%. The majority of patients (74.3%) enrolled following an ST elevation MI (STEMI).

Of the randomized patients, 56.9% of patients had acute signs of congestion that required treatment, and 78.3% had newly developed LV systolic dysfunction, with EF below 45%. “About 35% had of those characteristics overlap,” Butler said.

The primary outcome for EMPACT-MI will a composite of the time to first heart failure hospitalization (HHF) or all-cause mortality; according to clinicaltrials.gov, patients were enrolled up to 26 months.

Secondary outcomes listed are: (1) total number of HHF or all-cause mortality, (2) total number of non-elective cardiovascular (CV) hospitalizations or all-cause mortality, (3) total number of non-elective all-cause hospitalizations or all-cause mortality, (4) total number of hospitalizations for MI or all-cause mortality, and (5) time to CV mortality.

Butler compared the trial design to that of DAPA-MI, which concluded in July and evaluated the safety and effectiveness of dapagliflozin (Farixga, AstraZeneca) in the post-MI population. He noted key differences in the trial designs, notably that DAPA-MI enrolled patients within 10 days of MI and excluded patients with T2D; the primary end point is a composite of 7 characteristics, including mortality, hospitalization, atrial fibrillation, and new onset diabetes.

EMPACT-MI, Butler concluded, is evaluating empagliflozin in a group of patients who are not represented in other trials with SGLT2 inhibitors. “Hopefully the results will be available within the next few months,” he said.

Reference

Butler J. Baseline characteristics of patients enrolled in the EMPACT-MI trial. Presented at: European Society of Cardiology 2023 Congress, Amsterdam, the Netherlands; August 25-28, 2023. https://esc365.escardio.org/ESC-Congress/sessions/8115-drug-related-risk-management-in-chronic-coronary-syndromes