Can sacubitril-valsartan be used in a patient with hypotension?

Sacubitril/Valsartan Use in Patients with Hypotension (BP 95/45)

Sacubitril/valsartan should not be used in patients with a blood pressure of 95/45 mmHg due to high risk of symptomatic hypotension, which could worsen morbidity and mortality. 1, 2

Risk Assessment for Hypotension with Sacubitril/Valsartan

Sacubitril/valsartan exerts a more pronounced effect on blood pressure compared to ACEIs/ARBs, making it particularly risky in patients with pre-existing hypotension. The FDA label specifically warns about symptomatic hypotension as a significant adverse effect 2.

Key Risk Factors for Hypotension with Sacubitril/Valsartan:

• Systolic BP ≤100 mmHg (borderline BP) 1
• Volume depletion 1, 2
• Salt depletion 2
• Activated renin-angiotensin system 2
• Concomitant diuretic use 1

Evidence from Clinical Studies:

• In the PIONEER-HF trial, up to 25% of patients developed hypotension when treated with sacubitril/valsartan, even after hemodynamic stabilization 1
• The LIFE trial showed that 18% of advanced heart failure patients were intolerant to even low-dose sacubitril/valsartan (24/26 mg twice daily), with 59% of these cases due to SBP <90 mmHg 3
• A 2024 study found that hypotension after sacubitril/valsartan was associated with higher risk of cardiovascular death and HF hospitalizations (adjusted RR: 1.63) 4

Management Considerations

When BP is 95/45 mmHg:

• The current BP of 95/45 mmHg is already below the cautionary threshold of systolic BP ≤100 mmHg mentioned in guidelines 1
• The 2021 ACC Expert Consensus advises "careful administration and follow-up" even in borderline BP cases, suggesting extreme caution in already hypotensive patients 1
• The FDA label states: "Correct volume or salt depletion prior to administration of sacubitril and valsartan or start at a lower dose" 2

Alternative Approaches:

1. Address hypotension first:

   • Correct volume depletion if present
   • Consider reducing or discontinuing other hypotensive medications
   • Evaluate for and treat other causes of hypotension

2. If heart failure treatment is urgently needed:

   • Consider other guideline-directed medical therapies with less hypotensive effect
   • Mineralocorticoid receptor antagonists might be considered in conjunction with loop diuretics if renal function is adequate 1

Special Considerations

Potential Mitigation Strategies (if BP improves):

• In non-congested patients with stable clinical profiles, empiric modest lowering of loop diuretic doses may mitigate hypotensive effects of sacubitril/valsartan 1
• If BP improves to >100 mmHg, a gradual titration approach (6 weeks vs. 3 weeks) maximizes the chance of achieving target doses 5

Monitoring Requirements:

• Close blood pressure monitoring
• Serial assessment of electrolytes and renal function
• Symptoms of hypotension (dizziness, lightheadedness, syncope)

Conclusion

A blood pressure of 95/45 mmHg represents a clear contraindication to initiating sacubitril/valsartan therapy due to the high risk of symptomatic hypotension, which could lead to falls, syncope, decreased organ perfusion, and potentially increased mortality. The patient's blood pressure should be optimized before considering sacubitril/valsartan therapy.