Highlights
In stable post-myocardial infarction patients with left ventricular ejection fraction 40% or greater, a higher prerandomization heart rate remained associated with more hard cardiovascular events and higher all-cause mortality, even in the contemporary reperfusion era.
Baseline heart rate did not predict the ABYSS primary composite endpoint because that endpoint included cardiovascular rehospitalization, a frequent and broader outcome that may dilute associations with fatal and ischemic events.
Interrupting β-blockers increased heart rate by approximately 10 to 13 beats per minute during follow-up and was associated with worse outcomes regardless of baseline heart-rate tertile or ejection-fraction subgroup.
These findings strengthen the clinical case for continuing β-blockers after uncomplicated myocardial infarction in patients represented by ABYSS, while also reaffirming resting heart rate as a simple but meaningful risk marker.
Background
Resting heart rate has long been recognized as a marker of sympathetic tone, myocardial oxygen demand, and overall cardiovascular risk. In patients recovering from myocardial infarction, a higher heart rate has historically been associated with recurrent ischemic events, heart failure, arrhythmias, and death. Much of that evidence, however, comes from earlier treatment eras, before routine primary percutaneous coronary intervention, dual antiplatelet therapy, intensive lipid lowering, and widespread use of contemporary secondary prevention.
That evolution in care has raised an important clinical question: does heart rate still carry independent prognostic information after myocardial infarction when patients are revascularized, clinically stable, and treated with modern preventive therapies? A second question is even more practical. If β-blockers are interrupted beyond the first year after an uncomplicated infarction, is any potential harm modified by baseline heart rate? Put differently, can clinicians identify a lower-risk subgroup in whom withdrawal is neutral?
The ABYSS trial directly addressed β-blocker interruption versus continuation in stable post-MI patients with preserved or mildly reduced systolic function. The present prespecified secondary analysis focuses on heart rate, an especially relevant physiologic variable because β-blockers lower heart rate, reduce adrenergic drive, and may favorably influence ischemic threshold and arrhythmic vulnerability. The analysis therefore has immediate implications for post-MI risk stratification and long-term medical therapy.
Study Design
Trial framework
This report is a prespecified secondary analysis of the ABYSS trial, formally titled Assessment of Beta-Blocker Interruption 1 Year After an Uncomplicted Myocardial Infarction. The analysis included 3698 stable post-myocardial infarction patients already treated with β-blockers and randomized either to continue therapy or to interrupt it.
Population
Eligible participants had a prior myocardial infarction and were clinically stable at the time of randomization. All had left ventricular ejection fraction of at least 40%, meaning the trial largely reflects patients without significant systolic dysfunction. Median age was 63.5 years, with an interquartile range of 55.9 to 71.1 years. Women comprised 621 patients, or 17.1% of the cohort.
Heart-rate stratification
For this secondary analysis, patients were grouped by prerandomization heart-rate tertiles: less than 60 beats per minute, 60 to less than 68 beats per minute, and 68 beats per minute or greater. These groups permit a clinically intuitive comparison across low, intermediate, and relatively higher resting heart rates in a β-blocker-treated population.
Intervention and comparator
The therapeutic comparison remained the original randomized ABYSS strategy: β-blocker continuation versus β-blocker interruption. The current analysis examined whether baseline heart rate influenced treatment effects, and whether interruption materially altered on-treatment heart rate over time.
Endpoints
The primary endpoint was the ABYSS composite of death, myocardial infarction, stroke, or cardiovascular rehospitalization. Major secondary endpoints included narrower and clinically harder composites such as death, myocardial infarction, or stroke; death, myocardial infarction, stroke, or heart failure; and all-cause mortality. The distinction matters because broader composites may behave differently from hard-event endpoints when assessing a biomarker such as heart rate.
Key Findings
Baseline heart rate and the primary composite endpoint
Baseline heart rate was not associated with the trial’s primary endpoint. Event rates across the three tertiles were 22.4%, 21.8%, and 21.6%, respectively, with a P value of 0.867. On first reading, that might suggest heart rate has lost prognostic relevance in modern post-MI care. The deeper analysis argues against that conclusion.
The likely explanation is endpoint composition. The primary ABYSS endpoint included cardiovascular rehospitalization, which is clinically important but less specific than death, recurrent infarction, or stroke. Rehospitalization can reflect heterogeneous drivers including chest pain evaluation, arrhythmia monitoring, procedural planning, or decompensation of varying severity. When such events are frequent, they can obscure biologically tighter relationships between resting heart rate and harder cardiovascular outcomes.
Higher heart rate predicted hard ischemic and mortality outcomes
When the analysis turned to more specific event clusters, the expected prognostic gradient emerged clearly. The composite of death, myocardial infarction, or stroke occurred in 5.5% of patients in the lowest heart-rate tertile, 6.4% in the middle tertile, and 9.2% in the highest tertile. This difference was statistically significant with P less than 0.001. Comparing the highest with the lowest tertile, the adjusted hazard ratio was 1.55 with a 95% confidence interval of 1.14 to 2.12.
A similar pattern was seen for the composite of death, myocardial infarction, stroke, or heart failure: 6.5%, 7.1%, and 10.4% across ascending tertiles, with P equal to 0.007. The adjusted hazard ratio for the highest versus lowest tertile was 1.47, with a 95% confidence interval of 1.11 to 1.97.
All-cause mortality also rose across tertiles, from 2.9% to 3.4% to 5.9%, with P equal to 0.004 and a significant trend test of 0.008. This is particularly important because all-cause death is resistant to adjudication bias and captures the broad adverse biological burden that may accompany sustained adrenergic activation or greater underlying disease severity.
Effect of β-blocker interruption on heart rate
β-blocker interruption produced a substantial and clinically meaningful increase in heart rate during follow-up. The rise was described as dose-dependent and averaged approximately 10 to 13 beats per minute. That magnitude is large enough to matter physiologically. In a post-MI heart, even moderate heart-rate elevation can increase myocardial oxygen consumption, shorten diastolic perfusion time, reduce ischemic threshold, and potentially unmask latent susceptibility to recurrent ischemia or arrhythmia.
The finding also serves as an internal mechanistic signal. If interrupting β-blockers meaningfully increases heart rate, and higher heart rate is associated with worse hard outcomes, then heart-rate change becomes a plausible mediator of at least part of the observed clinical risk. This does not prove causality, but it adds biological coherence to the trial findings.
No evidence of a safe low-heart-rate subgroup for interruption
One of the most clinically actionable observations is that the association between β-blocker interruption and worse outcomes was consistent across baseline heart-rate tertiles. There was no significant interaction between prerandomization heart rate and treatment strategy. In practical terms, patients with lower baseline heart rates did not appear protected from the adverse consequences of stopping therapy.
This point deserves emphasis because clinicians often consider withdrawing β-blockers in stable, asymptomatic post-MI patients when resting heart rate is already low or normal. The present analysis does not support baseline heart rate as a tool for identifying a subgroup in whom interruption is clearly benign.
Consistency across ejection-fraction strata
The adverse association with β-blocker interruption was also consistent across left ventricular ejection-fraction categories of 40% to 49% and greater than 50%. That consistency broadens the relevance of the findings within the preserved or mildly reduced ejection-fraction spectrum represented in ABYSS. It suggests the signal is not confined to those with only mildly impaired ventricular function.
Clinical Interpretation
Why heart rate still matters in the reperfusion era
These data argue that heart rate remains clinically relevant after myocardial infarction despite modern reperfusion and secondary prevention. That should not be entirely surprising. Heart rate is not merely a number on the chart; it integrates autonomic balance, cardiorespiratory fitness, residual ischemic burden, medication effect, and possibly systemic inflammation or neurohormonal activation. In survivors of myocardial infarction, a higher resting heart rate may therefore identify patients with persistent biologic vulnerability even when conventional treatment milestones have been met.
The analysis also reminds clinicians that contemporary therapies do not eliminate fundamental pathophysiology. Revascularization reduces ischemic burden, statins stabilize plaque, and antithrombotic agents reduce thrombosis, but none fully abolishes the adverse hemodynamic consequences of a persistently elevated heart rate.
How to interpret the apparently neutral primary endpoint
The neutral relationship between baseline heart rate and the primary ABYSS composite should be interpreted cautiously rather than taken at face value as proof of no prognostic value. Composite endpoints are only as informative as their components are biologically aligned. Here, cardiovascular rehospitalization likely dominated event counts and diluted associations with more specific outcomes. The secondary endpoint findings are internally consistent, statistically robust, and clinically more persuasive for the prognostic role of heart rate.
Implications for long-term β-blocker therapy
For clinicians managing stable post-MI patients with preserved ejection fraction, the current analysis supports continued caution about elective β-blocker discontinuation. The message is not that heart rate is the sole reason to continue therapy, but that withdrawal predictably raises heart rate and that this occurs in the setting of outcome signals that do not meaningfully vary by baseline heart-rate category.
This is especially relevant because practice patterns vary widely after the first year following uncomplicated myocardial infarction. Some clinicians continue β-blockers indefinitely, whereas others stop them in the absence of angina, arrhythmia, or left ventricular dysfunction. ABYSS and this secondary analysis push the field toward more conservative continuation, at least in patients similar to those enrolled.
Mechanistic Considerations
The observed association is biologically plausible. A higher heart rate increases myocardial oxygen demand and reduces diastolic filling time, which in turn reduces coronary perfusion reserve, particularly in the presence of residual epicardial or microvascular disease. Elevated sympathetic activity may also promote endothelial dysfunction, arrhythmogenesis, and adverse ventricular remodeling. β-blockers counter many of these processes through heart-rate reduction, anti-ischemic effects, suppression of catecholamine-mediated electrical instability, and modest blood-pressure lowering.
At the same time, heart rate may also function as a marker rather than a direct causal factor. Patients with higher resting heart rates may have poorer cardiorespiratory fitness, more residual ischemia, more autonomic imbalance, or more comorbid burden. The adjusted analyses reduce but do not eliminate this possibility. The clinical value of heart rate, however, does not depend on resolving that distinction completely. A marker that is simple, reproducible, and strongly associated with hard outcomes can still be useful for risk assessment.
Strengths and Limitations
Strengths
This analysis has several notable strengths. It was prespecified, reducing concern about purely exploratory post hoc inference. It was embedded within a randomized trial, which strengthens comparisons related to β-blocker interruption versus continuation. The cohort was sizable at 3698 patients, and the heart-rate strata are clinically easy to interpret. The investigators also assessed both physiologic effect, namely heart-rate change, and clinical outcomes.
Limitations
Several limitations should shape interpretation. First, this is a secondary analysis, so causal statements regarding baseline heart rate itself remain limited. Second, the population was restricted to stable post-MI patients with left ventricular ejection fraction 40% or greater, so extrapolation to those with reduced ejection fraction, ongoing ischemia, recent instability, or significant arrhythmia should be cautious. Third, women represented only 17.1% of the cohort, which limits sex-specific inference.
Fourth, resting heart rate was categorized by tertiles rather than analyzed exclusively as a continuous exposure, which aids interpretability but can obscure nonlinear associations. Fifth, the abstract does not provide granular data on β-blocker class, dose intensity, adherence over time, concomitant rate-limiting drugs, rhythm status beyond broad eligibility, or causes of rehospitalization. Those factors may influence both heart rate and outcomes. Finally, because the abstract is the source material here, detailed information on funding and trial registration cannot be fully expanded beyond the citation provided.
Context Within the Literature and Guidelines
Current post-MI practice sits at the intersection of older β-blocker evidence and newer uncertainty in revascularized, lower-risk patients with preserved systolic function. Historical randomized trials established β-blockers as a cornerstone of post-infarction care, but many predated current reperfusion and preventive regimens. More recent observational studies and pragmatic analyses have generated mixed conclusions regarding the benefit of prolonged therapy in patients without heart failure or reduced ejection fraction.
The ABYSS program is therefore important because it addresses a contemporary and highly practical question using randomized data. This secondary analysis adds an important dimension by showing that heart rate continues to matter prognostically and that stopping therapy consistently increases heart rate without revealing a reassuring baseline heart-rate subgroup.
Guidelines have increasingly nuanced long-term β-blocker recommendations after myocardial infarction, especially for patients without reduced ejection fraction, heart failure, recurrent angina, or arrhythmia. Findings such as these are likely to influence future refinements by emphasizing patient selection, biologic response, and the ongoing prognostic relevance of resting heart rate.
Practical Takeaways for Clinicians
First, resting heart rate remains a useful bedside and clinic-based risk signal after myocardial infarction, even in a stable, contemporary population. A heart rate of 68 beats per minute or higher in this study was associated with meaningfully greater risk of death, recurrent myocardial infarction, stroke, and heart-failure-inclusive outcomes.
Second, if a stable post-MI patient is doing well on β-blockers, clinicians should be cautious about stopping therapy solely because the patient appears low risk or has a normal resting heart rate. In ABYSS, interruption increased heart rate by roughly 10 to 13 beats per minute and adverse effects were not confined to those with higher baseline heart rates.
Third, endpoint selection matters in interpretation. Broad composites that include rehospitalization may understate the prognostic importance of heart rate relative to more specific hard cardiovascular outcomes.
Fourth, the results are most applicable to stable post-MI patients with ejection fraction at least 40%. Management decisions in patients with reduced ejection fraction, symptomatic angina, atrial arrhythmias, conduction disease, or intolerance to β-blockers still require individualized judgment.
Conclusion
This prespecified secondary analysis of the ABYSS trial shows that higher resting heart rate remains associated with adverse cardiovascular events and all-cause mortality after myocardial infarction, even among stable patients treated in the modern reperfusion era and having preserved or mildly reduced ejection fraction. β-blocker interruption substantially increased heart rate and was linked with worse outcomes consistently across baseline heart-rate and ejection-fraction subgroups. Taken together, the data support two clinically relevant conclusions: resting heart rate still carries prognostic meaning after myocardial infarction, and baseline heart rate does not identify an obviously safe subgroup for β-blocker withdrawal.
Funding and ClinicalTrials.gov
The abstract provided does not detail funding support or the ClinicalTrials.gov registration number for this secondary analysis. Readers should consult the full Circulation publication and the primary ABYSS trial report for definitive funding, oversight, and registration information.
Citation
Zeitouni M, Procopi N, Cayla G, Ferrari E, Rangé G, Puymirat E, Delarche N, Guedeney P, Cuisset T, Varenne O, Cador R, Motreff P, Christiaens LP, Bellemain-Appaix A, Fayard M, Bayet G, Quédillac JM, Goube P, Goralski M, Elhadad S, Heliot F, Caussin C, Aisenfarb JC, Litalien J, Rambaud G, Attias D, Dumaine R, Slama MS, El Kasty M, Payot L, Aacha K, Diallo A, Vicaut E, Montalescot G, Silvain J, AβYSS investigators of the ACTION Study Group. Heart Rate and Cardiovascular Outcomes in Post-Myocardial Infarction Patients Treated by β-Blockers: A Secondary Analysis of the ABYSS Trial. Circulation. 2026-06-10. PMID: 42267437. URL: https://pubmed.ncbi.nlm.nih.gov/42267437/
Selected contextual literature: Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2018;39(2):119-177. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Circulation. 2013;127:e362-e425. Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407-477.
