Sacubitril Valsartan: An Overview
Sacubitril valsartan, commonly known by the brand name Entresto®, is a medication prescribed primarily for heart failure with reduced ejection fraction (HFrEF) and hypertension. It combines two active ingredients: sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker (ARB). This combination works by reducing the strain on the heart, but like any powerful medication, it can cause side effects. While many adverse events are similar across all age groups, older patients often have unique vulnerabilities due to underlying health conditions, polypharmacy, and age-related changes in physiology.
Common Side Effects in the Elderly
Older adults taking sacubitril valsartan may experience several common side effects. While generally manageable, these require close attention from both the patient and their healthcare provider.
Hypotension (Low Blood Pressure)
One of the most frequently reported side effects is low blood pressure. While this is expected to some degree, older adults may be more susceptible to symptomatic hypotension, which can lead to lightheadedness, dizziness, and fainting. This risk is compounded by other medications that also lower blood pressure and the presence of low left ventricular ejection fraction (LVEF).
- Managing Hypotension
- Monitor blood pressure regularly, especially when first starting the medication or adjusting the dose.
- Rise slowly from a sitting or lying position to prevent dizziness.
- Communicate any feelings of lightheadedness or weakness to your doctor promptly.
- Dosage may need to be adjusted cautiously in elderly patients to reach a maximum tolerated dose while minimizing adverse effects.
Hyperkalemia (High Potassium Levels)
This condition, marked by high potassium levels in the blood, is another potential concern. The valsartan component, an ARB, can contribute to increased potassium levels. While mild elevations may be asymptomatic, very high levels can be dangerous, causing irregular heartbeats or muscle weakness.
- Managing Hyperkalemia
- Blood tests are essential for regular monitoring of potassium levels.
- Dietary intake of high-potassium foods may need to be managed under medical supervision.
- It is less common than with ACE inhibitors, but patients with kidney issues or who take potassium-sparing diuretics are at higher risk.
Cough
A persistent dry cough is a possible side effect, though it is less common with sacubitril valsartan than with the older class of medications known as ACE inhibitors. It can still be bothersome and should be discussed with a doctor to determine its cause.
Age-Specific Concerns in Elderly Patients
Recent real-world data and pharmacovigilance studies have highlighted some side effects that may be more pronounced or uniquely concerning in the elderly population.
Increased Frailty and Physical Deconditioning
Older adults are inherently more vulnerable to frailty. Some studies have noted that sacubitril valsartan in patients over 65 might be associated with an increased risk of physical deconditioning, reduced exercise tolerance, and weight loss. These effects can exacerbate existing frailty, increasing the risk of falls and other complications. Closer monitoring and potential physical therapy support may be needed.
Cognitive-Related Adverse Events
While rare, some pharmacovigilance reports have suggested potential cognitive-related issues in patients aged 65 and older. These include impaired reasoning, distractibility, and memory impairment. The direct causal link is not yet clinically proven, but it underscores the need for caution and vigilant observation, especially in patients already at risk for cognitive decline.
Hyperuricemia
Studies have shown a significantly higher incidence of hyperuricemia (high uric acid levels) in elderly patients compared to younger adults. This is an important consideration as hyperuricemia can contribute to poor cardiovascular outcomes and needs careful management.
Renal Function
Sacubitril valsartan can cause a transient decline in kidney function, especially when first started. While the long-term effect often demonstrates renal protection, initial monitoring is key, particularly in older patients who may already have some degree of chronic kidney disease.
- Renal Function Comparison in Older Adults
| Feature | Sacubitril/Valsartan | Traditional RAS Inhibitors (e.g., Valsartan) |
|---|---|---|
| Effect on Renal Function | Associated with a transient initial eGFR decline, but often demonstrates long-term renal protection. | Can also cause renal function changes, but may offer less long-term renal protection compared to sacubitril/valsartan. |
| Early eGFR Decline | Mild to moderate declines (15-20%) may occur, but tend to recover and do not consistently predict adverse outcomes. | Early eGFR decline can occur, but the prognostic significance and long-term renal benefits compared to sacubitril/valsartan may differ. |
| Hyperkalemia | Lower incidence of hyperkalemia reported when compared to traditional renin-angiotensin-aldosterone system inhibitors. | Higher risk of hyperkalemia, especially in combination with mineralocorticoid receptor antagonists. |
Considerations for Prescribing and Monitoring
Given the unique profile of side effects in older patients, healthcare providers must exercise caution and follow best practices when prescribing and managing sacubitril valsartan.
- Individualized Dosing: The starting dose should be conservative, and titration should be slow and cautious, as many elderly patients achieve a lower maximum tolerated dose than younger adults.
- Comprehensive Monitoring: Regular monitoring of blood pressure, kidney function (via eGFR and creatinine), and serum potassium levels is essential. Patients should receive blood tests at baseline and at regular intervals during treatment.
- Patient Education: Clear communication about potential side effects, including symptoms of hypotension and hyperkalemia, is vital. Patients should be instructed to report any unusual symptoms promptly.
- Addressing Frailty: In patients prone to frailty, monitoring for changes in mobility, energy levels, and weight is critical to mitigate risks like falls.
- Interactions with Other Medications: The risk of side effects is heightened by polypharmacy. Careful review of all medications is necessary to identify and manage potential drug-drug interactions, particularly those affecting blood pressure and potassium levels.
Conclusion
While sacubitril valsartan offers significant benefits for older adults with heart failure, a comprehensive understanding of its side effect profile in this population is crucial. Increased susceptibility to hypotension, hyperuricemia, and potential links to worsened frailty and cognitive issues require vigilant monitoring and individualized treatment strategies. With careful management, including cautious dosing and regular lab work, elderly patients can safely and effectively benefit from this important medication. Consult with your healthcare provider for personalized advice and monitoring.
For More Information
For further reading on the management and safety of sacubitril valsartan in older adults, refer to published studies in reputable medical journals. For example, a thorough pharmacovigilance study can be found here: A real-world pharmacovigilance study of sacubitril/valsartan in older people: data mining of the FDA adverse event reporting system.
