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Another Beta-blocker Blow:

REDUCE AMI Confirms No
Benefit After Acute MI
The latest study to undermine the role of these long-standing
agents suggests their use harkens back to a bygone era.
by Michael O'Riordan APRIL 07, 2024
A
TLANTA, GA—The latest study to assess the long-term use of
beta-blockers in patients with acute MI and preserved ejection
fraction has again suggested that, in the modern era of post-MI
care, these agents do nothing to reduce the risk of death or recurrent MI.

Investigators reported the results of the registry-nested REDUCE-AMI

randomized trial today at the American College of Cardiology 2024
Scientific Session.

Among more than 5,000 patients who presented with either STEMI or
NSTEMI and who underwent coronary angiography during the
hospitalization, all-cause mortality or MI occurred in 7.9% of those
treated with a beta-blocker and in 8.3% of those who did not receive a
beta-blocker (HR 0.96; 95% CI 0.79-1.16). Additionally, there was no
benefit in any of the secondary endpoints or in any prespecified
subgroups.

While there are historic data supporting the use of beta-blockers,

including their currently recommended spot in the clinical guidelines,
lead investigator Troels Yndigegn, MD (Lund University/Skane
University Hospital, Sweden), and colleagues say those data are simply
too antiquated.

“These results are from trials that mainly involved patients with large
myocardial infarctions and left ventricular systolic dysfunction and were
conducted primarily in the 1980s,” they write in the New England
Journal of Medicine paper published to coincide with the late-breaking
clinical trial session. “This era predates advancements such as high-
sensitivity cardiac troponins, percutaneous coronary interventions,
antithrombotic agents, high-intensity statins, and renin–angiotensin–
aldosterone system antagonists.”

To address the question in a more contemporary era, the REDUCE-AMI

investigators performed a parallel-group, open-label trial at 45 hospitals
in Sweden, Estonia, and New Zealand using registry data. More than 95%
of patients were from Sweden, with data on MI collected from the
SWEDEHEART registry and mortality through a linked national
database. In Estonia and New Zealand, baseline data were collected
using electronic case-report forms similar to those used in
SWEDEHEART and follow-up through hospital health records.
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. Between 2017 and 2023, 2,508 were treated
with metoprolol succinate (62.2%) to a target dose of 100 mg or
bisoprolol (37.8%) to a target dose of 5.0 mg and 2,512 were not treated
with any beta-blocker. More than one-third (35%) presented with STEMI
and more than 95% underwent PCI. At discharge, 97% were treated with
aspirin, approximately 96% were treated with a P2Y12 receptor
antagonist, and nearly all patients received a statin.

Over a median follow-up of 3.5 years, there was no difference in the risk
of the primary endpoint (all-cause mortality or MI), nor in any of the
secondary endpoints, between those who were treated with beta-
blockers and those who were not.

“The doses of beta-blockers that were used in our trial were lower than
those in previous trials,” write the REDUCE-AMI researchers. “However,
the doses that were used in our trial mirror the current practice of beta-
blocker treatment, and no apparent association between the planned
target dose of beta-blocker treatment and the primary endpoint was
observed.”

Maybe Not Finished Yet?

In an editorial, P. Gabriel Steg, MD (Hôpital Bichat, Assistance Publique-

Hôpitaux de Paris, France), points out that the incidence of the primary
endpoint—2.4% and 2.5% per year in the beta-blocker and no beta-
blocker arms, respectively—was much lower than anticipated by the
investigators, likely because these were patients with near-normal LVEF
who’d undergone revascularization and received excellent care. The
results do not apply to higher-risk patients, such as those with LVEF <
50% or those who haven’t undergone revascularization.

Steg points out that a double-blind randomized trial is preferable to an

open-label design, noting that crossover at 1 year was not negligible: 18%
of those taking beta-blockers stopped in the first year while 14% of those
randomized to no treatment started. Moreover, he reminds physicians
that “absence of evidence is not evidence of absence,” adding that
confidence intervals do include a potential 21% lower risk with beta-
blockers.
“Given the difficulty of unambiguously showing an absence of benefit
with beta-blocker therapy and the limitations of a single, somewhat
underpowered, open-label trial, it may be too early to cut beta-blockers
from the secondary prevention team’ definitively. While we await the
results of the multiple upcoming trials reevaluating the role of beta-
blockers in contemporary care, it may be prudent to place routine beta-
blocker therapy after myocardial infarction on ‘injured reserve.’”

More studies of post-MI patients randomized to beta-blockers or not

should help clarify things further, with DANBLOCK, BETAMI, REBOOT,
and AβYSS all expected in 2024, as well as SMART-DECISION and
ABBREVIATE to come after that, writes Steg.

by Michael O'Riordan
Michael O’Riordan is the Associate Managing Editor for TCTMD and
a Senior Journalist. He completed his undergraduate degrees at
Queen’s… Read Full Bio

SOURCES DISCLOSURES COMMENTS

Yndigegn T, Lindahl B, Mars K, et al. Beta-blockers after myocardial

infarction and preserved ejection fraction. N Engl J Med. 2024;Epub
ahead of print.

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