BIO-GUARD-MI Questions Post-MI Therapy Guided by Rhythm Monitor

Treatable arrhythmias picked up by insertable cardiac monitors (ICM) were unexpectedly common in patients with a recent or remote history of myocardial infarction (MI) in a randomized trial. But the study’s primary finding questioned whether ICM-guided management of such arrhythmias makes a difference to cardiovascular (CV) risk.

The BIO-GUARD-MI trial was “negative” for its primary outcome; that is, no significant difference in major adverse cardiac events (MACE) emerged over about 2.5 years between post-MI patients assigned to ICM-guided management or to standard care.

That was despite ICM monitoring’s apparent success in unmasking potentially important arrhythmic events. Arrhythmias leading to initiation of a therapy were identified in almost 40% of the ICM group, compared with about 7% of the standard-care group.

Still, there were suggestions in the trial, some only hypothesis-generating, that ICM-guided post-MI management may well have benefited some types of patients more than others.

The strategy made zero difference to outcomes, for example, among patients with a history of ST-segment elevation MI (STEMI), whereas those in the ICM group with previous non-STEMI (NSTEMI) showed a 31% reduction (P = .035) in risk for MACE.

That suggests continuous ICM monitoring can reveal asymptomatic but clinically important arrhythmias that can guide treatment decisions, perhaps improving clinical outcomes, in patients with previous NSTEMI, proposed the trial’s lead investigator, electrophysiologist Christian Jøns, MD, PhD, Rigshospitalet, Copenhagen.

Jøns presented the BIO-GUARD-MI results and exploratory analyses April 4 at the American College of Cardiology (ACC) 2022 Scientific Session, held both virtually and in-person in Washington, DC.

The trial entered patients at elevated risk on the basis of CHA2DS2-VASc score, which had to be greater than 4 in men and 5 in women. It was set up so that any arrhythmias were adjudicated by a central monitoring committee, but patients received care from their own physicians or at local hospitals.

Therapies — most often oral anticoagulation, beta blockers, or pacemaker implantation — were initiated a median of 4 days after the ICM event that prompted them, Jøns reported.

“Missing a Lot of Events”

Patients with recent MI who are considered high risk — “especially if there’s a low ejection fraction, and we’re worried about arrhythmias” — are often referred to an electrophysiologist, observed Roxana Mehran, MD, at a press conference on the trial held during the ACC sessions.

“But we’re not really doing this routinely,” added Mehran, fromm the Icahn School of Medicine at Mount Sinai, New York City, who isn’t connected to BIO-GUARD-MI. The trial, which showed “a huge number” of arrhythmic events in the ICM group, compared with those assigned to standard care, “makes you think that maybe we’re missing a lot of events.”

The BIO-GUARD-MI investigators assigned 790 patients — average age, 71 years and 72% male — to receive or not receive an ICM at 60 sites in Australia, Europe, and the United States. They could have neither atrial fibrillation (AF) nor an implanted pacemaker or defibrillator.

Therapy for an arrhythmia, including AF in 46% and bradycardia in 39%, was added to management in 39.0% of the ICM group and in 6.7% of the group without ICM, Jøns reported. Such treatment most often consisted of oral anticoagulants, pacemakers, or beta blockers.

The MACE hazard ratio (HR) in the ICM group, compared with those in the standard-care group, was nonsignificant, at 0.84 (95% CI, 0.64 – 1.10; = .21). As defined in the trial, MACE consisted of CV death, heart failure hospitalization, arrhythmia, acute coronary syndrome, stroke, major bleeding, and systemic embolism.

The corresponding HR was nonsignificant, at 1.10 (95% CI, 0.72 – 1.69; P = .66), in the subgroup with a history of STEMI, but significant, at 0.69 (95% CI, 0.49 – 0.98; P = .035), in those with previous NSTEMI, although there was only a trend for interaction (P = .09).

Why NSTEMI but Not STEMI?

Further analysis was undertaken to determine whether the contrasting results for NSTEMI and STEMI patients were “just a coincidence or a true signal,” Jøns said. The analysis showed a significantly increased risk for the primary endpoint (HR, 1.75; 95% CI, 1.33 – 2.30; = .0003) in NSTEMI patients, compared with STEMI patients.

That may explain how ICM-guided management could work better in NSTEMI patients; the greater MACE risk in the NSTEMI group than in the STEMI group implies more potential for a significant treatment effect, Jøns proposed.

Support for that interpretation came from analysis of other MACE risk factors in the trial, he said. Patients were categorized as either high or low risk for MACE based on features that independently predicted the outcome in multivariate analysis. These included obesity, heart failure, peripheral vascular disease, and acute or subacute MI as opposed to chronic-phase MI.

The MACE risk for ICM patients was significantly reduced for those at high risk (HR, 0.57; 95% CI, 0.38 – 0.86), but not for those at low risk (HR, 1.11; 95% CI, 0.79 – 1.59).

Given the BIO-GUARD-MI trial’s negative primary finding, it remains unanswered whether instituting post-MI therapy based on ICM-identified events makes a difference to outcomes, Mehran said at the press conference. “And so, it would be good to have larger, prospective randomized studies.”

The study was funded by BIOTRONIK. Jøns discloses consulting for BIOTRONIK as BIO-GUARD-MI coordinating investigator; and having a consultancy agreement with Abbott for lecture activities. Mehran discloses receiving consultant fees or honoraria from the Cine‐Med Research Institute; fully divested equity interest in Boston Scientific; ownership interest, a partnership, or other principal role at ControlRad; receiving research grants from Abbott Laboratories, Abiomed, Alleviant Medical, AM‐Pharma, Arena, AstraZeneca Pharmaceuticals, Bayer Healthcare Pharmaceuticals, Biosensors, Biotronik, Boston Scientific, Bristol‐Myers Squibb, Cardiawave, CellAegis, Celonova Biosciences, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Element Science, Humacyte, Idorsia Pharmaceuticals, Insel Gruppe AG, Janssen, Magenta, Medtronic, Novartis, OrbusNeich, Philips, VivaSure, and Zoll; and holding stock in Applied Therapeutics, Elixir Medical, and STEL.

American College of Cardiology (ACC) 2022 Scientific Session: Abstract 410-14. Presented April 4, 2022.

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