In patients undergoing major non‑cardiac or cardiac surgery who have coronary artery disease, hypertension, heart failure, or left‑ventricular ejection fraction ≤40%, how should peri‑operative neurohormonal therapy (beta‑blockers, angiotensin‑converting‑enzyme inhibitors/angiotensin‑II receptor blockers, aldosterone antagonists, statins) be managed?

Perioperative Neurohormonal Therapy Management in High-Risk Surgical Patients

Continue beta-blockers, ACE inhibitors/ARBs, and statins perioperatively in patients with established cardiovascular disease undergoing major surgery, but hold ACE inhibitors/ARBs 24 hours before surgery if feasible to reduce hypotension risk, and never initiate beta-blockers on the day of surgery. 1, 2

Beta-Blocker Management

Continuation of Existing Therapy (Strongest Recommendation)

• Beta-blockers must be continued in all patients already receiving them for coronary artery disease, heart failure, hypertension, or arrhythmias to prevent rebound hypertension and increased mortality (RR 2.70 for MI within 30 days of cessation). 1, 2

• Target heart rate should be 60-70 beats/min with systolic blood pressure maintained >100 mmHg. 1, 2

• Abrupt withdrawal dramatically increases cardiovascular mortality and postoperative MI risk, making continuation a Class I indication. 2, 3

Initiation of New Beta-Blocker Therapy

High-risk patients (≥3 clinical risk factors or known CAD) undergoing vascular surgery:

• Start beta-blockers 2-7 days (ideally 30 days) before surgery to allow dose titration and assessment of tolerability. 1, 2
• Use beta-1 selective agents (metoprolol, atenolol, bisoprolol) without intrinsic sympathomimetic activity. 1
• This approach reduces cardiac mortality and MI in high-risk vascular surgery patients. 1

Intermediate-risk patients (1-2 clinical risk factors):

• Beta-blockers should be considered (Class IIa recommendation) for intermediate-risk surgery. 1

Low-risk patients (0 risk factors):

• Do not initiate beta-blockers - evidence shows increased mortality (OR 1.19,95% CI 1.06-1.35) in this population. 1, 4

Critical Safety Principles

• Never start beta-blockers on the day of surgery - this increases mortality, stroke, hypotension, and bradycardia without adequate time for dose optimization. 2, 3

• Hold beta-blockers if heart rate <50 bpm or systolic blood pressure <100 mmHg. 2, 3

• Monitor for bradycardia (RR 2.22,95% CI 1.50-3.29) and hypotension (OR 1.84,95% CI 1.31-2.59), which are significantly increased with perioperative beta-blockade. 2, 5

Intravenous Beta-Blocker Administration

For patients unable to take oral medications:

• Administer IV metoprolol 2.5 mg slow bolus over 1-2 minutes, repeatable every 5 minutes up to maximum 15 mg total dose. 3
• Alternative: IV atenolol 5-10 mg given 30 minutes before surgery. 3
• Alternative: Esmolol infusion 100-300 mcg/kg/min (ultra-short half-life of 9 minutes allows rapid titration). 3

Mandatory pre-administration checks:

• Verify no heart failure, systolic BP ≥100 mmHg, heart rate ≥50 bpm, no heart block, no active asthma. 3
• Continuous cardiac monitoring required during IV administration. 3

Transition to oral therapy:

• Resume oral metoprolol 15 minutes after last IV dose, starting with 25-50 mg every 6 hours for 48 hours. 3

ACE Inhibitor/ARB Management

Evidence-Based Approach

Hold ACE inhibitors/ARBs 24 hours before noncardiac surgery - recent large cohort data demonstrates patients who stopped these medications had lower rates of death, stroke, myocardial injury, and intraoperative hypotension compared to those continuing therapy. 1

Continuation Indications

• Continue ACE inhibitors/ARBs perioperatively in hemodynamically stable patients with good renal function and normal electrolytes. 1, 6

• Mandatory continuation in patients with LVEF ≤40%, heart failure, or post-MI status (Class I indication). 1

• Consider continuation in patients with hypertension, diabetes, or chronic kidney disease where cardiovascular risk factors are well-controlled. 1

Special Considerations

• Among lower-risk patients with normal LVEF and well-controlled risk factors post-revascularization, ACE inhibitor use may be optional (Class IIa). 1

• ARBs are recommended for patients intolerant of ACE inhibitors who have heart failure or post-MI with LVEF ≤40%. 1

Aldosterone Antagonist Management

Continue aldosterone antagonists in post-MI patients with LVEF ≤40% who have diabetes or heart failure and are already receiving therapeutic ACE inhibitor and beta-blocker doses, provided no significant renal dysfunction or hyperkalemia exists. 1

• This represents a Class I indication based on mortality benefit. 1

• Verify creatinine <2.5 mg/dL (men) or <2.0 mg/dL (women) and potassium <5.0 mEq/L before continuation. 1

Statin Management

Continue statins perioperatively in all patients with established cardiovascular disease - this is reasonable for vascular surgery regardless of clinical risk factors (Class IIa). 1

• Consider starting statins in patients with ≥1 clinical risk factor undergoing intermediate-risk procedures (Class IIb). 1

• Long-term statin therapy should be continued or initiated in patients with clinical indications who are undergoing major surgery. 6

Cardiac Surgery-Specific Considerations

For cardiac surgery patients:

• Beta-blocker continuation is even more critical given the 2.70-fold increased mortality risk with discontinuation. 2

• All neurohormonal agents with Class I indications (beta-blockers for angina/arrhythmias, ACE inhibitors for LVEF ≤40%, aldosterone antagonists for appropriate post-MI patients) must be continued. 1, 2

• Aspirin should be started within 48 hours after CABG to reduce saphenous vein graft closure (100-325 mg/day). 1

Common Pitfalls to Avoid

• Never initiate high-dose beta-blockers without titration - perioperative high-dose beta-blockers without titration are not recommended (Class III). 1

• Do not withdraw beta-blockers or clonidine abruptly - both cause rebound hypertension and increased cardiac events. 1, 6

• Avoid starting beta-blockers in patients with absolute contraindications - asthma, severe conduction disorders, symptomatic bradycardia, symptomatic hypotension (Class III). 1

• Monitor closely when combining warfarin with antiplatelet agents - increased bleeding risk requires careful surveillance. 1

• Beta-blockers are not contraindicated in intermittent claudication and may reduce mortality in COPD patients undergoing vascular surgery. 1