Should Angiotensin-Converting Enzyme (ACE) inhibitors be stopped prior to surgery?

Should ACE Inhibitors Be Stopped Prior to Surgery?

For most patients undergoing elevated-risk noncardiac surgery with controlled blood pressure, withhold ACE inhibitors 24 hours before surgery to reduce intraoperative hypotension, but continue them in patients with heart failure with reduced ejection fraction (HFrEF). 1, 2

Primary Recommendation Based on Most Recent Evidence

The decision depends critically on the indication for ACE inhibitor therapy:

Patients with Hypertension (Without HFrEF)

• Withhold ACE inhibitors 24 hours before elevated-risk noncardiac surgery 1, 2
• This approach reduces intraoperative hypotension by approximately 37% without increasing mortality or major adverse cardiovascular events (MACE) 3
• The European Society of Cardiology specifically recommends holding these medications 24 hours preoperatively in hypertensive patients 2

Patients with Heart Failure with Reduced Ejection Fraction

• Continue ACE inhibitors perioperatively under close monitoring 1, 2
• The cardioprotective benefits in this population outweigh the risk of intraoperative hypotension 2
• Abrupt discontinuation may precipitate heart failure decompensation 1

Evidence Supporting This Approach

Key Clinical Trial Data

• Recent large randomized controlled trials (POISE-3 and Stop-or-Not) demonstrated no difference in cardiovascular death, myocardial injury, stroke, or cardiac arrest between continuation versus discontinuation strategies 4
• However, continuation was associated with significantly more intraoperative hypotension requiring vasopressor support 3, 4
• Meta-analysis of 6,022 patients showed 50% experienced hypotension when continuing ACE inhibitors on the day of surgery, but without differences in death, MI, stroke, or kidney failure 5

Guideline Recommendations

The 2024 American College of Cardiology guidelines provide nuanced recommendations:

• Class IIb recommendation (may be beneficial): Omit ACE inhibitors 24 hours before elevated-risk surgery in patients with controlled blood pressure 1
• Class IIa recommendation (reasonable): Continue ACE inhibitors perioperatively in general 5
• The more restrictive 2024 recommendation reflects newer evidence showing benefits of withholding in select patients 1

Postoperative Management

Restart ACE inhibitors as soon as clinically feasible postoperatively once hemodynamic stability and adequate volume status are achieved 5, 1, 6, 2

Key considerations for restarting:

• Ensure the patient is hemodynamically stable with adequate blood pressure 6
• Confirm volume status is appropriate to prevent postoperative hypotension 6, 2
• Monitor blood pressure closely after reinitiation 6
• Inappropriate discontinuation after surgery is associated with worse long-term cardiovascular outcomes 5

Common Pitfalls and How to Avoid Them

Pitfall 1: Failing to Distinguish Between Indications

• Avoid: Applying a blanket approach to all patients on ACE inhibitors
• Solution: Specifically identify whether the patient has HFrEF (continue) versus hypertension alone (consider withholding) 1, 2

Pitfall 2: Inadequate Communication

• Avoid: Unclear instructions about which medications to take on the morning of surgery
• Solution: Provide explicit written instructions specifying to hold ACE inhibitors 24 hours before surgery if that is the plan 1

Pitfall 3: Forgetting to Restart Postoperatively

• Avoid: Leaving ACE inhibitors discontinued after discharge, leading to rebound hypertension or heart failure decompensation
• Solution: Document clear plans for medication resumption and ensure follow-up 5, 1

Pitfall 4: Overreacting to Intraoperative Hypotension

• Avoid: Viewing intraoperative hypotension as a catastrophic complication
• Solution: Recognize that while hypotension is more common with continuation, it responds readily to vasopressors without adverse outcomes 5, 7

Clinical Decision Algorithm

Step 1: Identify the primary indication for ACE inhibitor therapy

• If HFrEF → Continue perioperatively 1, 2
• If hypertension without HFrEF → Proceed to Step 2

Step 2: Assess surgical risk and blood pressure control

• If elevated-risk surgery AND controlled blood pressure → Withhold 24 hours before surgery 1
• If low-risk surgery → Continuation is reasonable 5

Step 3: Ensure adequate vasopressor availability

• Anticipate need for increased intraoperative vasopressor support if continuing 3

Step 4: Plan postoperative restart

• Resume when hemodynamically stable with adequate volume status 6, 2

Strength of Evidence Considerations

The evidence base has evolved significantly:

• Older 2014 ACC/AHA guidelines favored continuation (Class IIa) based on observational data showing no harm despite hypotension 5
• More recent 2024-2025 guidelines incorporate newer randomized trial data, leading to more selective withholding recommendations 1
• The shift reflects recognition that while major adverse events are equivalent, reducing intraoperative hypotension may simplify anesthetic management without compromising outcomes 4