Can Entresto (sacubitril/valsartan) cause hypotension?

Entresto (Sacubitril/Valsartan) and Hypotension

Yes, Entresto (sacubitril/valsartan) commonly causes hypotension, with both symptomatic and asymptomatic forms documented in clinical trials. 1, 2

Incidence and Risk of Hypotension with Entresto

• 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 1
• Hypotension was identified as a key predictor of non-completion during the run-in phase of the PARADIGM-HF trial 1
• The FDA label explicitly lists "low blood pressure (hypotension)" as a common side effect during treatment with sacubitril/valsartan 2
• In the PIONEER trial, despite precautions to prevent treatment-induced hypotension, symptomatic hypotension occurred in 15% of patients in the sacubitril/valsartan group 1

Risk Factors for Hypotension with Entresto

• Concomitant use of diuretics increases the risk of hypotension, as stated in the FDA label: "Your risk of low blood pressure is greater if you also take water pills (diuretics)" 2
• Patients in acute heart failure settings have higher rates of hypotension events compared to those with chronic heart failure 1
• Patients with lower baseline blood pressure may be at particular risk during initiation of therapy 1
• The LIFE trial showed that hypotension or hypotensive symptoms were primary reasons for discontinuing even low-dose sacubitril/valsartan in advanced heart failure 1

Clinical Presentation and Management

• Symptoms of hypotension may include dizziness, lightheadedness, and extreme fatigue 2
• The FDA label advises: "Call your doctor if you become dizzy or lightheaded, or you develop extreme tiredness (fatigue)" 2
• Dose adjustments may be necessary for patients who develop hypotension: "Your doctor may need to lower your dose, temporarily stop treatment, or permanently stop treatment if you develop certain side effects" 2
• Despite the risk of hypotension, the 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 1

Special Considerations

• Interestingly, patients with the lowest baseline systolic blood pressure (95-110 mmHg) often experience a mild blood pressure increase over time with sacubitril/valsartan treatment 1
• In the STRONG-HF study, despite close monitoring, hypotension occurred in 5% of patients in the high-intensity implementation group compared to 1% in usual care 1
• Orthostatic hypotension was reported in 0.6% of patients receiving intensive heart failure therapy that included sacubitril/valsartan 1
• The PIONEER trial implemented specific precautions to prevent hypotension, including maintaining systolic blood pressure >100 mmHg for 6 hours before administration and ensuring clinical stability 1

Clinical Implications

• 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 1
• Careful monitoring of blood pressure is essential when initiating and titrating sacubitril/valsartan 2
• Starting at lower doses may be appropriate for patients with lower baseline blood pressure or those at higher risk for hypotension 1
• The clinical benefits of sacubitril/valsartan on mortality and heart failure outcomes may outweigh the risk of hypotension in appropriate patients 1