Empagliflozin did not cut risk for death, HF hospitalization after heart attack: EMPACT-MI
Click Here to Manage Email Alerts
Key takeaways:
- In patients with an acute MI, empagliflozin did not reduce risk for the primary endpoint of death or heart failure hospitalization.
- The empagliflozin group had reduced risk for certain HF-related outcomes.
ATLANTA — In the EMPACT-MI trial, empagliflozin treatment soon after an acute MI did not significantly lower risk for HF hospitalization or death from any cause compared with placebo among patients with increased risk for HF.
Although the trial did not meet its primary endpoint, patients assigned empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) had lower risk for certain outcomes directly related to HF, according to the researchers.
Presenting the findings at the American College of Cardiology Scientific Session, Javed Butler, MD, MPH, MBA, FACC, FAHA, FESC, president of the Baylor Scott and White Research Institute, senior vice president for Baylor Scott and White Health and distinguished professor of medicine at University of Mississippi, reported a 10% relative risk reduction in time to first hospitalization or all-cause death — the primary endpoint of the trial — among patients assigned daily empagliflozin within 14 days of admission for acute MI compared with placebo, but said it did not reach statistical significance.
Over nearly 18 months of follow-up, hospitalization for HF or death from any cause occurred in 8.2% of patients assigned empagliflozin and 9.1% of patients assigned placebo (HR = 0.9; 95% CI, 0.76-1.06; P = .21), according to results of the late-breaking clinical trial.
Main findings
Despite advances in management of acute MI, many patients remain at high risk for developing HF. Prognosis is especially poor for those who develop congestion or left ventricular dysfunction following acute MI, Butler said during the presentation. Previous research demonstrated that SGLT2 inhibitors can reduce CV outcomes in patients with HF, type 2 diabetes and high CV risk, and chronic kidney disease. However, the safety and efficacy of empagliflozin post-MI were unknown, according to the researchers.
EMPACT-MI was a large-scale clinical trial conducted at 451 sites in 22 countries. Researchers randomly assigned 6,522 patients who were hospitalized for acute MI and were at risk for HF to receive daily empagliflozin 10 mg or placebo in addition to standard care within 14 days after admission. High risk for HF was defined as signs or symptoms of congestion requiring treatment (57% of patients) or newly developed left ventricular ejection fraction of less than 45% (78.4% of patients). No patient had a previous diagnosis of chronic HF.
Most patients were men (75%), white (83%), older than 65 years (50%) and presented with STEMI (74.3%). One-third had type 2 diabetes and 13% had a prior MI. Revascularization was performed in most patients (89.3%).
“We found that empagliflozin did not reduce mortality after a heart attack, but did reduce the risk of heart failure after heart attack,” Butler said in an ACC press release. “To have a 25% to 30% reduction in HF hospitalizations is pretty clinically meaningful, but if you put it together with all-cause mortality, it was not a positive study for our primary endpoint.”
When the researchers looked at individual components of the primary endpoint, there was no significant difference between empagliflozin and placebo for all-cause death (HR = 0.96; 95% CI, 0.78-1.19), but there was a significant reduction in time to first hospitalization for HF in favor of empagliflozin (HR = 0.77; 95% CI, 0.6-0.98; P = .03), according to Butler.
Other key findings were as follows:
- Total HF hospitalizations or all-cause mortality: RR = 0.87 (95% CI, 0.68-1.1); P = .24
- Total nonelective CV hospitalizations or all-cause mortality: RR = 0.92; 95% CI, 0.78-1.07); P = .29
- Total nonelective all-cause hospitalizations or all-cause mortality: RR = 0.87; 95% CI, 0.77-1); P = .046
- Total MI hospitalizations or all-cause mortality: RR = 1.06 (95% CI, 0.83-1.35); P = .63)
- Total number of HF hospitalizations: RR = 0.67 (95% CI, 0.51-0.89); P = .006)
- Total number of adverse events of HF: RR = 0.63 (95% CI, 0.5-0.79); P < .001)
- Total number of adverse events of HF or all-cause mortality: RR = 0.79 (95% CI, 0.63-0.98); P = .031)
“Empagliflozin demonstrated 23% and 33% relative risk reduction of first hospitalization for HF and total hospitalizations for HF, components of the primary and first key secondary endpoints, respectively,” Butler said during the presentation. Moreover, he highlighted the 37% relative risk reduction in total HF events, as looked through the lens of HF adverse events, including in the outpatient setting.
Risk reduction for hospitalization for HF was consistent in subgroups and sensitivity analyses, Butler said.
Safety findings were consistent with the known safety profile of empagliflozin, Butler said.
Adverse events occurred in about one-quarter of patients in both groups and adverse events leading to permanent discontinuation in 3.8% in both groups. There was no significant difference in the risk for kidney injury.
Totality of evidence
Taken together, Butler said “the totality of evidence suggests the benefit of empagliflozin for heart failure risk reduction in patients post-acute MI without prior heart failure.” The EMPACT-MI results are “consistent with the benefit demonstrated with empagliflozin in other trials in adjacent patient populations.”
The recent DAPA-MI trial also looked at the effects of an SGLT2 inhibitor after acute MI, this time with dapagliflozin. (Read Healio’s full article on DAPA-MI here.) But there are key differences between DAPA-MI, which was a positive trial, and EMPACT-MI, including the exclusion of patients with diabetes in DAPA-MI.
The results of the EMPACT-MI trial “help fill the gap in knowledge” about the impact of SGLT2 inhibitors post-MI, according to the researchers.
During a discussion following the trial, James L. Januzzi, MD, the Hutter Family Professor of Medicine at Harvard Medical School, cardiologist at Massachusetts General Hospital and director of heart failure and biomarker trials at the Baim Institute for Clinical Research in Boston, said these are exciting results from a challenging study.
“I look at studies of medical therapy in acute MI as a ‘good news, bad news’ kind of story — which is to say that ... as in the case of the EMPACT-MI trial, which involved enrichment with a high risk factor as well as an increase in the sample size ... we can see that the event rates overall are quite low. That’s the good news. ... But on the other hand, there was still a hazard present in these patients. Understanding who is going to be at risk for developing HF symptoms despite excellent medical care in the cath lab and medical therapies after the cath lab remains an important exercise that we all have to think very, very carefully about. ... As a trialist, I look at the results and I see a neutral primary endpoint but then a really remarkable set of secondary follow-up findings,” Januzzi said.
Reference:
Perspective
Back to Top
This study reflects the real world. For example, I was just in the CCU with a patient with an EF in the 40s who was 3 days after an MI. I was not 100% sure of the data to support using an SGLT2 inhibitor in that setting. I reviewed DAPA-MI with my residents and fellows. It was designed differently from EMPACT-MI because it used win ratios, and it was driven by metrics like improvement in N-terminal pro-B natriuretic peptide and quality of life.
In EMPACT-MI, we did not see an improvement in the composite outcome of CV mortality and first hospitalization for HF. We can tell from the presentation and the paper that the HF hospitalization component of that seems to have been improved. While the totality of evidence seems to support initiation of an SGLT2 inhibitor across the spectrum of ejection fraction, that is really parsing out data. These results are surprising because we really thought SGLT2 inhibitors would work in every single setting. But in the post-acute MI setting, we are not seeing the same results as we did in other settings such as diabetes and the entire spectrum of HF. And I interpret DAPA-MI as a neutral study that did not show real clinical benefit, because the win ratio was not driven by clinical events. This does give you pause.
But that is not to say that I won’t start an SGLT2 inhibitor after an initial period of stabilization. In this study, initiation was done within 14 days of an MI. So maybe you could do it in the outpatient setting. However, it is humbling to realize that it does not work in every single situation.
Perspective
Back to Top
I think, in aggregate, these medications are safe and the SGLT2 inhibitors may have a role in reducing HF events in people with acute MI. I was particularly interested in Dr. Butler’s comments about the difference between patients who had non-STEMI vs. STEMI, and whether there is a signal of greater benefit, when stratified by the type of MI.
We have more to learn about the risk score that might enable us to target this therapy to the appropriate patients. As Dr. Butler mentioned, can you determine who is at higher risk and who is likely to derive the greatest benefit from the use of these medications? I think it is a work in progress, but it is a safe intervention and may have benefit.
Collapse
Butler J, et al. Joint American College of Cardiology/Journal of the American College of Cardiology Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; April 6-8, 2024; Atlanta.
Click Here to Manage Email Alerts