Should the angiotensin‑receptor neprilysin inhibitor (ARNI) sacubitril/valsartan be held before a surgical procedure?

Should ARNI Be Stopped Before Surgery?

Continue sacubitril/valsartan through the perioperative period in patients on stable doses, as there is no evidence of increased harm and emerging data suggests it may be safely continued without increased vasoplegia or adverse outcomes.

Rationale and Evidence

The 2024 AHA/ACC perioperative guideline 1 does not specifically address ARNI management, but provides clear direction for similar cardiovascular medications: medications with established long-term indications should be continued perioperatively, as acute discontinuation causes harm. The FDA labeling 2 warns about hypotension, renal dysfunction, and hyperkalemia but does not mandate preoperative discontinuation—rather, it advises dose adjustment or temporary interruption only if these complications occur.

Key Supporting Data

Safety Profile in Cardiac Surgery

Recent prospective data from cardiac surgery patients demonstrates that sacubitril/valsartan can be safely continued perioperatively 3, 4:

• No increased vasoplegia: 24-hour Vasoactive-Inotropic Scores were identical between exposed and non-exposed patients (21.5 vs 21.4, p=0.86) 3
• No increased vasopressor requirements: Duration of norepinephrine and dobutamine use were similar 3
• Potential benefits: Improved renal function by postoperative day 3 and reduced postoperative atrial fibrillation (12.7% vs 38.0%, p=0.0034) 4
• Discontinuation rate: Only 10 of 63 patients (15.9%) required discontinuation due to hypotension, with no serious adverse events 4

Extrapolation from RAAS Inhibitor Data

While specific ARNI data is limited, the broader RAAS inhibitor literature is relevant 5, 6, 7:

• Withholding ACEIs/ARBs reduces intraoperative hypotension but with very low certainty of evidence 5
• The SPACE trial showed continuing ACEIs/ARBs was safe, with potential benefit in patients with low NT-proBNP 7
• Discontinuation increases postoperative hypertension risk 5

Clinical Algorithm

For patients on stable ARNI therapy:

1. Continue through surgery if:

   • Hemodynamically stable preoperatively
   • No recent hypotensive episodes
   • Normal or near-normal renal function
   • Heart failure is well-compensated

2. Consider holding on day of surgery if:

   • History of significant intraoperative hypotension in prior surgeries
   • Volume-depleted state (high-dose diuretics)
   • Baseline systolic BP <100 mmHg
   • eGFR <30 mL/min/1.73m²

3. Monitor closely perioperatively for:

   • Hypotension (most common reason for discontinuation) 2
   • Acute kidney injury (monitor creatinine) 2
   • Hyperkalemia (check potassium) 2

Important Caveats

• Heart failure patients: Abrupt discontinuation risks decompensation—the indication for ARNI (typically HFrEF) makes continuation particularly important
• Hemodynamic management: Have vasopressors readily available; treat hypotension with fluids and vasopressors rather than permanently discontinuing ARNI 2
• Restart timing: If held, resume when hemodynamically stable, typically 24-48 hours postoperatively once adequate oral intake established
• Black patients: Higher angioedema risk—monitor airway closely 2

The evidence favors continuation over routine discontinuation, with individualized decisions based on hemodynamic stability and renal function rather than blanket policies.