From the Guidelines
Yes, Entresto (sacubitril/valsartan) can cause hypotension as one of its common side effects. This is due to its mechanism of action, which combines an angiotensin receptor blocker (valsartan) that relaxes blood vessels with sacubitril, a neprilysin inhibitor that increases levels of natriuretic peptides, promoting sodium excretion and vasodilation 1. Patients starting Entresto or having their dose increased should be monitored for symptomatic hypotension, which may present as dizziness, lightheadedness, or fainting, especially during the initial period of treatment.
Key Considerations
- The risk of hypotension is higher in patients who are volume-depleted, elderly, have severe renal impairment, or are taking other medications that lower blood pressure such as diuretics, ACE inhibitors, or ARBs.
- To minimize this risk, healthcare providers typically recommend starting at a lower dose (usually 24/26 mg twice daily) and gradually titrating up to the target dose of 97/103 mg twice daily as tolerated 1.
- Patients should be advised to stay adequately hydrated, avoid sudden position changes, and report symptoms of low blood pressure.
Monitoring and Management
- Regular blood pressure monitoring is essential, especially in the initial stages of treatment or when the dose is adjusted.
- Patients with a history of angioedema should not be administered ARNI therapy due to the increased risk of recurrence 1.
- Concomitant use of ACE inhibitors and ARNI is contraindicated due to the potential for increased risk of angioedema and hypotension 1.
From the FDA Drug Label
Low blood pressure (hypotension). Low blood pressure can happen with valsartan tablet, especially when you first start taking it and can cause you to feel lightheaded In controlled trials in heart failure patients, the incidence of hypotension in valsartan-treated patients was 5. 5% compared to 1.8% in placebo-treated patients. If excessive hypotension occurs, place the patient in the supine position and, if necessary, give intravenous normal saline.
Entresto (sacubitril/valsartan) can cause low blood pressure (hypotension), especially when first starting treatment or in certain patient populations, such as those with heart failure or post-myocardial infarction. The incidence of hypotension in clinical trials was higher in valsartan-treated patients compared to placebo-treated patients. Patients should be monitored for signs of hypotension and treated accordingly. 2 2
From the Research
Entresto and Low Blood Pressure
- Entresto (sacubitril/valsartan) is a medication used to treat heart failure with reduced ejection fraction.
- According to the study published in 2016 3, sacubitril/valsartan was found to cause symptomatic hypotension more commonly than the angiotensin converting enzyme (ACE) inhibitor enalapril.
- A 2022 study 4 analyzed the tolerability of sacubitril/valsartan in patients with advanced heart failure and found that 18% of subjects were intolerant of the medication, with reasons for intolerance including systolic blood pressure <90 mm Hg (59%) and symptoms of hypotension/dizziness with systolic blood pressure >90 mm Hg (19%).
- The same study 4 identified predictors of intolerance to sacubitril/valsartan, including lower mean arterial pressure, lower serum chloride, and presence of an implantable cardioverter-defibrillator and/or cardiac resynchronization device.
Clinical Implications
- The studies suggest that Entresto can cause low blood pressure (hypotension) in some patients, particularly those with advanced heart failure.
- Patients taking Entresto should be monitored for signs of hypotension, such as dizziness or lightheadedness, and their blood pressure should be regularly checked 3, 4.
- The benefits of Entresto in improving clinical symptoms and prognosis in patients with heart failure should be weighed against the potential risk of hypotension 5.