# Perioperative Beta-Blocker Management — ACC/AHA 2014

## Overview

Perioperative beta-blocker management is one of the most extensively studied and debated areas in perioperative cardiac care. The 2014 ACC/AHA guideline provides nuanced recommendations based on the POISE trial, multiple observational studies, and a dedicated systematic review of perioperative beta blockade in noncardiac surgery. The guideline takes a more conservative approach to beta-blocker initiation compared to earlier guidelines, while strongly endorsing continuation in patients already receiving therapy.

## Beta-Blocker Recommendations

### Continuation of Beta-Blockers (Class I)

- **Beta-blockers should be continued in patients undergoing surgery who have been on beta-blockers chronically.** (Class I, Level of Evidence: B)
- This applies to patients receiving beta-blockers for any established indication (e.g., heart failure, coronary artery disease, rate control of atrial fibrillation, hypertension, migraine).
- Abrupt withdrawal of beta-blockers perioperatively can lead to rebound tachycardia and hypertension and is associated with increased risk of adverse cardiac events.

### Initiation of Beta-Blockers: When to Consider

#### Elevated Risk with Preoperative Ischemia (Class IIb)

- It **may be reasonable** to begin perioperative beta-blocker therapy in patients with intermediate- or high-risk myocardial ischemia noted in preoperative risk stratification (e.g., abnormal stress testing). (Class IIb, Level of Evidence: C)

#### RCRI >= 3 Risk Factors (Class IIb)

- It **may be reasonable** to begin perioperative beta-blocker therapy in patients with **3 or more RCRI risk factors** (e.g., diabetes mellitus, heart failure, coronary artery disease, renal insufficiency, cerebrovascular disease). (Class IIb, Level of Evidence: B)
- Observational data suggest that patients with >= 3 RCRI risk factors appear to benefit from perioperative beta-blocker use.

#### Long-Term Indication (Class IIb)

- It **may be reasonable** to begin beta-blockers before surgery in patients with a long-term (nonperioperative) indication for beta-blocker therapy but who are not currently on one. (Class IIb, Level of Evidence: C)

### When Beta-Blocker Initiation Is NOT Recommended (Class III)

- **Beta-blocker therapy should NOT be started on the day of surgery** in patients who are beta-blocker naive. (Class III: Harm, Level of Evidence: B)
- The POISE trial (PeriOperative Ischemic Evaluation) demonstrated that initiating extended-release metoprolol succinate 2 to 4 hours before surgery reduced nonfatal MI but significantly **increased** the risks of:
  - All-cause mortality (3.1% vs. 2.3%; HR 1.33)
  - Stroke (1.0% vs. 0.5%; HR 2.17)
  - Clinically significant hypotension (15.0% vs. 9.7%)
  - Clinically significant bradycardia (6.6% vs. 2.4%)
- These findings underpin the Class III (Harm) recommendation against day-of-surgery initiation.

### Uncertain Benefit (Class IIb)

- The usefulness of perioperative beta-blocker therapy in patients with **1 or 2 RCRI risk factors** is **uncertain**. (Class IIb, Level of Evidence: B)
- The net benefit-to-harm ratio is less clear in patients with fewer risk factors.

## Timing and Dosing of Initiation

When the decision is made to initiate perioperative beta-blocker therapy:

- **Start 2 to 7 days before surgery** to allow assessment of clinical effectiveness and tolerability. Few data support initiation > 30 days before surgery.
- Begin with a low dose and titrate to a target resting heart rate of **60 to 80 bpm**.
- Avoid starting at high doses without titration (as was done in the POISE trial with metoprolol succinate 200 mg).
- Optimal dosing and titration protocols have not been definitively established, but gradual titration is important to avoid hemodynamic instability from hypotension and/or bradycardia.

### Specific Beta-Blockers Referenced in the Evidence Base

| Beta-Blocker | Key Trials | Notes |
|---|---|---|
| **Metoprolol succinate** | POISE trial | Extended-release; POISE used fixed-dose 200 mg protocol; associated with increased stroke and mortality when started day of surgery |
| **Bisoprolol** | DECREASE trials (Poldermans et al.) | Cardioselective; DECREASE trials suggested benefit but have been subject to concerns regarding data integrity |
| **Atenolol** | Mangano et al. (1996) | Associated with reduced mortality at 6 months and 2 years in early studies; subsequent analyses have been less consistent |

- The guideline does not mandate a specific beta-blocker for perioperative initiation. However, cardioselective agents (metoprolol, bisoprolol, atenolol) are generally preferred.

## Heart Rate Targets

- **Target resting heart rate: 60 to 80 bpm** when initiating or titrating perioperative beta-blockers.
- Avoid heart rate < 55 bpm and systolic blood pressure < 100 mmHg.
- The POISE trial protocol (targeting heart rate <= 80 bpm but using a fixed high dose) resulted in excess hypotension and bradycardia, emphasizing the importance of titration over fixed-dose protocols.

## Summary Decision Algorithm for Perioperative Beta-Blockers

1. **Patient already on beta-blocker for any indication?**
   - Yes: **Continue** perioperatively. (Class I, Level of Evidence: B)
   - No: Proceed to step 2.

2. **Has a long-term (nonperioperative) indication for beta-blocker therapy?**
   - Yes: **May be reasonable** to start before surgery if time permits. (Class IIb, Level of Evidence: C)
   - No: Proceed to step 3.

3. **RCRI >= 3 risk factors?**
   - Yes: **May be reasonable** to start beta-blocker 2-7 days before surgery. (Class IIb, Level of Evidence: B)
   - No: Proceed to step 4.

4. **Intermediate- or high-risk ischemia on preoperative stress testing?**
   - Yes: **May be reasonable** to start beta-blocker. (Class IIb, Level of Evidence: C)
   - No: Beta-blocker initiation is not recommended for perioperative risk reduction.

5. **Day of surgery and patient is beta-blocker naive?**
   - **Do NOT initiate.** (Class III: Harm, Level of Evidence: B)

## Special Populations

### Patients with Heart Failure

- Continue beta-blocker therapy in patients with heart failure already receiving it (these patients are typically on beta-blockers as part of GDMT for HFrEF).
- Use caution when initiating beta-blockers in patients with decompensated heart failure, as they may worsen hemodynamic status.

### Patients Undergoing Vascular Surgery

- Vascular surgery patients represent the highest-risk surgical population. Observational data supporting perioperative beta blockade have primarily been drawn from vascular surgery cohorts.
- The balance of benefit (MI reduction) versus risk (stroke, hypotension) must be carefully weighed.

### Patients with Reactive Airway Disease

- Beta-blockers are relatively contraindicated in patients with severe reactive airway disease (asthma, severe COPD with bronchospastic component).
- If beta-blocker therapy is essential, use a cardioselective agent (bisoprolol, metoprolol) at the lowest effective dose.

## POISE Trial Summary

The POISE trial (2008) is the largest randomized controlled trial of perioperative beta blockade (n = 8351):
- **Intervention**: Metoprolol succinate 200 mg extended-release started 2-4 hours before surgery, continued for 30 days.
- **Primary endpoint**: Composite of cardiovascular death, nonfatal MI, and nonfatal cardiac arrest at 30 days.
- **Key findings**:
  - Reduced nonfatal MI (3.6% vs. 5.1%; HR 0.73)
  - Increased all-cause death (3.1% vs. 2.3%; HR 1.33)
  - Increased stroke (1.0% vs. 0.5%; HR 2.17)
  - Increased clinically significant hypotension (15.0% vs. 9.7%)
  - Increased clinically significant bradycardia (6.6% vs. 2.4%)
- The net effect was harmful, primarily due to excess deaths and strokes attributed to hypotension.

## Limitations

- Most beta-blocker recommendations carry Level of Evidence B or C, reflecting the limited number of large, well-conducted randomized trials.
- The DECREASE trial family, which suggested strong benefit for bisoprolol, has been discredited due to concerns about research integrity (Poldermans et al.). The 2014 guideline was written with awareness of these concerns.
- The optimal dose, timing, and specific beta-blocker agent for perioperative initiation remain undefined.
- The Class IIb designation for most initiation recommendations reflects genuine clinical equipoise -- the decision should be individualized.
- The guideline does not address perioperative beta-blocker management for patients undergoing cardiac surgery.
