Can Entresto (sacubitril/valsartan) be used in a patient with hypotension and reduced left ventricular ejection fraction?

Can Entresto Be Used in Patients with Low Blood Pressure and Reduced Ejection Fraction?

Yes, Entresto (sacubitril/valsartan) can and should be used in patients with reduced ejection fraction even when blood pressure is low, as the mortality benefit is maintained across all baseline blood pressure categories, including systolic BP as low as 95-110 mmHg. 1, 2

Key Principle: Asymptomatic Hypotension Should Not Prevent Treatment

• Asymptomatic hypotension is not a contraindication to initiating or uptitrating Entresto. The drug maintains efficacy and safety regardless of baseline blood pressure, even in patients with systolic BP <110 mmHg. 1

• Benefits of sacubitril/valsartan were maintained across all baseline systolic blood pressure categories in the PARADIGM-HF trial, including in patients with lower baseline blood pressure. 2

• Patients with the lowest baseline systolic blood pressure (95-110 mmHg) often experience a mild blood pressure increase over time with sacubitril/valsartan treatment, paradoxically improving their hypotension. 2

Practical Initiation Strategy for Low Blood Pressure Patients

Starting Dose Selection

• For patients with borderline blood pressure (systolic BP ≤100 mmHg), start with the lowest dose of 24/26 mg twice daily rather than the standard 49/51 mg dose. 1

• The European Society of Cardiology endorses starting at "low-dose" in patients with orthostatic hypotension and low blood pressure. 3

• Consider maintaining systolic blood pressure >100 mmHg for 6 hours before administration when initiating in hospitalized patients. 2

Titration Approach

• Uptitrate slowly with small increments every 2-4 weeks as tolerated, targeting the full dose of 97/103 mg twice daily for maximum mortality benefit. 1, 3

• Increase dose every 1-2 weeks by small increments: 24/26 mg BID → 49/51 mg BID → 97/103 mg BID. 3

• Blood pressure may actually improve over time as cardiac output increases with effective heart failure therapy, allowing further uptitration. 3

Managing Symptomatic Hypotension

When to Reduce Diuretics First

• If symptomatic hypotension occurs, reduce diuretic dose first in non-congested patients rather than reducing Entresto, as this often resolves the issue without compromising guideline-directed medical therapy. 1

• Evaluate and address reversible causes of hypotension including overdiuresis, non-HF antihypertensive medications, dehydration, or valvular disease. 3

When to Temporarily Reduce Entresto

• Consider temporarily reducing the dose rather than discontinuing therapy completely, as 40% of patients who required temporary dose reduction were subsequently restored to target doses. 1

• Symptomatic hypotension with systolic BP <80 mmHg warrants dose reduction. 3

• Severe orthostatic symptoms interfering with daily activities despite patient education may require dose adjustment. 3

Patient Education Strategy

• Counsel patients that mild transient dizziness upon standing is an expected side effect of life-prolonging medications and does not necessarily require dose reduction. 3

• Confirm the orthostatic hypotension is truly problematic by assessing whether the patient has significant symptoms (severe dizziness, syncope, fatigue) versus asymptomatic low blood pressure readings. 3

Clinical Trial Data on Hypotension Risk

• In the PARADIGM-HF trial, 16.0% of patients experienced asymptomatic hypotension and 11.1% experienced symptomatic hypotension at least once after randomization to sacubitril/valsartan. 2

• Despite the risk of hypotension, guidelines suggest that low blood pressure should not necessarily prevent optimization of guideline-directed medical therapy that includes sacubitril/valsartan. 2

• The clinical benefits of sacubitril/valsartan on mortality and heart failure outcomes outweigh the risk of hypotension in appropriate patients. 2

Critical Pitfalls to Avoid

• Do not withhold Entresto entirely due to low blood pressure alone—patients with reduced ejection fraction desperately need RAAS blockade for mortality benefit. 3

• Do not fail to titrate to target doses due to asymptomatic hypotension or mild laboratory changes. 1

• Do not permanently reduce doses when temporary reductions with subsequent re-titration would be more appropriate. 1

• Do not assume orthostatic hypotension is caused by Entresto if the patient was stable on therapy previously; look for other causes first. 3

Monitoring Requirements

• Monitor blood pressure, renal function, and serum potassium at baseline and regularly during titration, with particular vigilance when combined with mineralocorticoid receptor antagonists. 1

• Monitor serum creatinine and eGFR routinely, especially when used with aldosterone antagonists. 1

• Caution when serum potassium levels >5.0 mmol/L, particularly when Entresto is combined with mineralocorticoid receptor antagonists. 1