Beta Blocker Interruption Causes Heart Rate Rebound and Worse CV Outcomes in Post-MI Patients: New Pre-Specified Analysis of ABYSS Trial

Beta-blocker interruption causes significant heart rate rebound and increased CV risk in patients with elevated baseline heart rate; while heart rate control below 60 bpm is associated with lower mortality (2.9% vs 5.9%) and fewer major adverse cardiovascular events (5.5% vs 9.2%) compared to heart rate ≥68 bpm in post-MI patients with LVEF ≥40%, a pre-specified ABYSS trial analysis has reported.

The analysis included 3,623 stable post-MI patients with left ventricular ejection fraction (LVEF) ≥40% who were randomized to β-blocker interruption or continuation. Patients were stratified into three groups based on pre-randomization heart rate tertiles: <60 bpm (n=1,220, median HR 55 bpm), 60-<68 bpm (n=1,149, median HR 63 bpm), and ≥68 bpm (n=1,254, median HR 75 bpm).

Key findings from this pre-specified analysis study include:

● β-Blocker Interruption Caused Dose-Dependent Heart Rate Rebound with Increased Cardiovascular Risk: β-blocker interruption led to significant and sustained heart rate increases with a dose-dependent rebound effect and higher cardiovascular event risk across all three heart rate tertiles, though more pronounced in patients with elevated baseline heart rate (≥68 bpm). The rebound was observed as early as 6 months and persisted throughout a 48-month follow-up (Figure 1). 

Figure 1: Heart Rate Changes Over Time by Baseline HR Tertile and Treatment Group

This figure demonstrates heart rate trajectory over 48 months in three baseline tertiles (T1: <60 bpm, T2: 60-<68 bpm, T3: ≥68 bpm) comparing β-blocker continuation (solid lines) versus interruption (dashed lines). Beta-blocker interruption resulted in sustained heart rate elevation across all tertiles, with the most pronounced rebound in patients with higher baseline heart rates.

Figures 1 and 2 illustrate the distribution of clinical outcomes across heart rate tertiles (HR <60 bpm, HR 60–<68 bpm, and HR ≥68 bpm). Figure 1 presents individual endpoints — all-cause mortality, cardiovascular death, and recurrent myocardial infarction — while Figure 2 depicts composite outcomes including MACE, MACE with heart failure hospitalization, and the primary composite endpoint.

Figure 2: Individual Clinical Endpoints: All-Cause Mortality, CV Death, Recurrent MI. All-Cause Mortality:p <0.001, Cardiovascular Death: p = 0.014, Recurrent MI: p = 0.040

Figure 2: Composite Endpoints: MACE, MACE + HF Hospitalization, Primary Composite. MACE: p <0.001, MACE + HF Hospitalization: p <0.001, Primary Composite Endpoint: p = 0.867 (Not Significant)

It is important to note that the ABYSS trial predominantly included patients receiving bisoprolol. Bisoprolol is distinguished by its high β1-selectivity, relatively long half-life, and sustained receptor occupancy, pharmacological characteristics that may likely influence physiological responses following treatment interruption. As the trial largely evaluated bisoprolol rather than comparing different β-blockers, the findings should be interpreted in the context of the agent studied and may not be generalized across the entire β-blocker class.

This study’s findings indicate that β-blocker interruption led to heart rate rebound with corresponding increases in cardiovascular events; reinforcing the importance of β-blocker continuation in post-MI patients.

Clinical Parameters for β-Blocker Discontinuation in Post-MI Patients

Speaking to Medical Dialogues, Dr. Swapan Kumar Saha, MBBS, MD (General Medicine), DM (Cardiology), said- "The ABYSS analysis gives us an important message about stopping beta blocker after myocardial infarction. When beta blockers were stopped, there was a noticeable rebound increase in heart rate. This increase in heart rate was maintained during follow-up. A higher heart rate was associated with a higher risk. of cardiovascular events. Stopping beta blocker did not show any clear benefit compared with continuing them. In fact, cardiovascular outcomes appeared to be less favorable after beta blocker interruption. This effect was seen irrespective of the patient's baseline heart rate or LV function. Therefore, we should be very careful about routinely stopping beta blockers in stable post MI patients. The decision to stop treatment should be based on the individual patient's clinical condition and tolerance. The take Home message is if a post MI patient is tolerating beta blocker therapy well, there is no strong reason to stop it routinely."

Heart Rate, Treatment Continuation, and Patient Outcomes Following MI

Speaking to Medical Dialogues, Dr. Samshad Alam, MBBS, MD (Medicine), DM (Cardiology), FSCAI (USA), said- "Patients continuing β-blockers post-MI tend to have better HR control and fewer ischemic episodes. ABYSS links interruption to HR rebound and CV events and ongoing therapy basically reduces MACE discontinuations. Ultimately the outcomes depend on dose, comorbidities, and function, so I try to tailor dosage (e.g., bisoprolol 1.25–10 mg) based upon the individual tolerability. In post MI patients now the target heart rate is 50 BPM in my clinical practice, never want it to be away from range of 50-70 BPM. This target achievement leads to decrease myocardial oxygen demand as well as less myocardial stress. So as a result, myocardial dysfunction slows down and muscle stiffness improves with decreased events of heart failure."

Post-MI β-Blocker Continuation: Better Heart Rate Control and Reduced Ischemic Risk

Speaking to Medical Dialogues, Dr. Jay Sanghavi, MBBS, MD, DrNB Cardiology, said- "Continuing β-blockers after MI usually yields better HR control and fewer ischemic events. As ABYSS has shown rebound with interruption, same way I have also seen these patterns. Ongoing therapy is associated with fewer MACE-related discontinuations. Dosing would vary between 1.25–10 mg for bisoprolol and I also adjust for tolerability and CV risk."