After Acute MI, REDUCE-AMI confirms no benefit

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Sripal Bangalore, MD (NYU Langone Health, New York, NY), who led that meta-analysis, is pleased there are finally randomized data to address this clinical question.
Each advance results in this new treatment being added to what’s worked in the past, resulting in patients taking multiple drugs after MI.
More than 95% of patients were from Sweden, with data on MI collected from the SWEDEHEART registry and mortality through a linked national database.
Patients with acute MI (median age 65 years; 22.5% female) who underwent coronary angiography and who had obstructive CAD and a preserved LVEF (≥ 50%) were randomized to treatment with a beta-blocker or no treatment.
Five or 10 years ago, beta-blockers were considered the bedrock of evidence, the cornerstone of treatment for MI.
Sripal Bangalore To TCTMD, Bangalore acknowledged that REDUCE-AMI does have limitations given that it’s a registry-based randomized trial, but nonetheless should change minds when it comes to the reflexive habit of prescribing beta-blockers after acute MI.
“In acute MI, at least in our clinical practice, we will start patients on other therapies, and maybe prescribe a beta-blocker towards the end, maybe before discharge,” he said.
Five or 10 years ago, beta-blockers were considered the bedrock of evidence, the cornerstone of treatment for MI.

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Atlanta, Georgia—The most recent study evaluating the long-term use of beta-blockers in patients with acute MI and preserved ejection fraction has once again raised concerns about the lack of efficacy of these medications in the current post-MI care era in terms of lowering the risk of death or recurrent MI.

The trial’s principal investigator, Troels Yndigegn, MD (Lund University/Skane University Hospital, Sweden), presented the findings of the registry-nested REDUCE-AMI randomized trial today at the American College of Cardiology (ACC) 2024 Scientific Session. The data revealed that the two treatment groups’ Kaplan-Meier curves for the primary endpoint of death or recurrent MI were “intermingling, virtually overlapping.”.

The broad recommendation for beta-blockers after acute MI is likely to be downgraded by senior investigator Tomas Jernberg, MD, PhD (Danderyd Hospital/Karolinska Institutet, Stockholm, Sweden). However, he feels comfortable not starting post-MI patients on beta-blockers as long as the LVEF is not compromised.

A number of observational studies, including REACH and CLARIFY, have suggested that there is no benefit to giving beta-blockers in addition to current medical therapy, challenging the use of these drugs in the post-MI era. Therefore, the REDUCE-AMI study is not the first to raise concerns about this practice. The risk of all-cause mortality in the reperfusion era was not found to be decreased by beta-blockers prescribed after acute MI, according to a 2014 meta-analysis of over 60 trials involving 100,000 patients.

Finally, randomized data to address this clinical question is a relief for the lead author of the meta-analysis, Sripal Bangalore, MD (NYU Langone Health, New York, NY).

“It’s true that we’ve been given a lot of therapies over the years,” he said to TCTMD. Patients who have a MI often take multiple medications as a result of each advancement adding a new treatment to what has previously worked. But according to Bangalore, “if you closely look at the data, you wonder if many of the [older] trials would pass muster in this day and age.”.

Being on numerous medications following a heart attack presents a significant challenge. Batchelor, Wayne.

According to Wayne Batchelor, MD, chair of the ACC interventional council at Inova Heart and Vascular Institute in Fairfax, Virginia, REDUCE-AMI permits doctors to treat patients with a “somewhat reductionist” approach. “Being on a ton of medications after a heart attack is one of the biggest challenges,” Batchelor said. “With a certain level of assurance, we can now state that you probably don’t need to include that if your left ventricular ejection fraction (LV ejection fraction) is preserved—that is, greater than 50%—and you don’t have any additional reasons to take a beta-blocker. “.

In conjunction with the ACC presentation, the new study was published in the New England Journal of Medicine.

Randomized Study Using a Registry.

Though those trials were carried out in the 1970s and 80s and preceded the modern era of PCI, high-sensitivity troponin testing, and modern medical management with statins, antithrombotic therapy, and ACE inhibitors/ARBs, Jernberg explained to TCTMD that there are “very solid data” showing that beta-blockers reduce the risk of mortality after a large MI in patients with impaired left ventricular function.

The routine use of beta-blockers in all ACS patients carries a 2a endorsement in the European guidelines, while they are recommended as class Ia in patients with LVEF ≤ 40%. According to US guidelines, doctors should start beta-blockers in patients with ACS who have STEMI (class I recommendation, level of evidence B) and in patients with NSTE-ACS who have low systolic function (class I, level of evidence C and class IIa, level of evidence C, respectively).

Using registry data, the REDUCE-AMI investigators conducted a parallel-group, open-label trial at 45 hospitals in Sweden, Estonia, and New Zealand to examine the efficacy of beta-blocker therapy in a more modern age. With data on MI obtained from the SWEDEHEART registry and mortality obtained from a linked national database, over 95% of the patients were from Sweden. Baseline data were gathered in Estonia and New Zealand through hospital health records for follow-up and electronic case-report forms akin to those used in SWEDEHEART.

A beta-blocker treatment or no treatment was randomly assigned to patients with acute MI (median age 65 years; 22.5% female) who underwent coronary angiography, had obstructive CAD, and a preserved LVEF (≥ 50%). Metoprolol succinate (62.2%) or bisoprolol (37.8%) at a target dose of 100 mg or 5 mg, respectively, were administered to 2,508 patients between 2017 and 2023, while 2,512 patients received no beta-blocker treatment at all. A third or more (35%) of the patients had STEMI, and over 95% of them had PCI. At the time of discharge, 97% of the patients were taking aspirin, 96% were taking a P2Y12 receptor antagonist, and almost all of the patients were taking a statin.

For a median follow-up of three point five years, all-cause mortality or MI occurred in 7 points 9 percent of the more than 5,000 patients who presented with either STEMI or NSTEMI and underwent coronary angiography during the hospitalization (HR 0.96; 95 percent CI 0.79-1.16) and in 8 points 3 percent of the non-beta-blocker patients. Furthermore, there was no advantage in any of the predefined subgroups or secondary endpoints.

While LVEF was typically compromised after MI prior to the development of coronary revascularization and other treatments, Batchelor stated that REDUCE-AMI primarily addresses a historical issue with regard to TCTMD.

He told TCTMD, “We’re not seeing these really low ejection fractions that we used to.”. The fact that guidelines supported the worldwide use of beta-blockers after myocardial infarction meant that, although they are still present and many of them tragically enter cardiogenic shock, the beta-blockers were used to treat all of the cardiac survivors. We can now hone that thanks to the findings of this study. “.

While Batchelor acknowledges that the study’s beta-blockers are the most effective medications, he questions the degree to which the drugs were coerced into the trial, given that the researchers’ data only extends one year into the future. Furthermore, there was no difference in the treatment arms’ safety endpoints, such as bradycardia and other arrhythmias, suggesting that the drugs may not have been administered at their highest possible dose.

He said, “There’s a chance we could be missing a little bit of therapeutic value there if they weren’t pushed to the max.”.

Bangalore, Batchelor, and others noted that the incidence of the primary endpoint—2 percent and 2.5 percent annually in the beta-blocker and no beta-blocker arms, respectively—was significantly lower than the investigators’ initial projections. This was probably due to the fact that the patients were near-normal LVEF patients who had undergone revascularization and were receiving excellent care.

According to Batchelor, “it’s indicative of how well we’re treating patients otherwise.”. “The interventional care provided to these patients was excellent. They were all taking P2Y12 inhibitors, aspirin, and statins. Consequently, it is just not possible to pick up a beta-blocker signal in the sphere of all those interventions. “.

Bangalore stated, “It just shows you how far we’ve come along in treating MI.”.

Possibly Not Completed Yet?

As per an editorial, P. Physician Gabriel Steg (Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, France) notes that the findings are limited to the patients included in the study and do not extend to patients at higher risk, such as those without revascularization or with LVEF < 50%. While crossover at one year was not insignificant—18% of beta-blocker users stopped in the first year, compared to 14% of those randomly assigned to no treatment—Steg notes that a double-blind randomized trial is better than an open-label design. He also adds that confidence intervals do include a possible 21% lower risk with beta-blockers and reminds doctors that "absence of evidence is not evidence of absence.". It might be premature to remove beta-blockers from the secondary prevention team permanently given the challenges of clearly demonstrating a lack of benefit with beta-blocker therapy and the limitations of a single, somewhat underpowered, open-label trial. It could be wise to put routine beta-blocker therapy on "injured reserve" following a myocardial infarction while we wait for the outcomes of the numerous upcoming trials that will reevaluate the role of these drugs in modern care. "". Additional randomized trials examining beta-blockers after MI should help elucidate the situation further. According to Steg, DANBLOCK, BETAMI, REBOOT, and AβYSS are anticipated in 2024, followed by SMART-DECISION and ABBREVIATE. Beta-blockers were regarded as the gold standard of evidence and the mainstay of MI treatment five or ten years ago. Bangalore-based Sripal. Bangalore informed TCTMD that although REDUCE-AMI is a registry-based randomized trial and therefore has limitations, it should nevertheless cause a shift in the reflexive practice of prescribing beta-blockers following acute MI. "In our clinical practice, we will initiate patients on alternative therapies for acute MI, and we may recommend a beta-blocker as a last resort, possibly even prior to discharge," the speaker stated. "People are receptive to [stopping beta-blockers] at the moment this trial is taking place. A decade or so ago, beta-blockers were regarded as the gold standard of evidence and the mainstay of MI treatment. Yet I believe the timing is right, and I have hope that things will turn around. ".

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