Entresto (Sacubitril/Valsartan) and Blood Pressure Reduction
Yes, Entresto (sacubitril/valsartan) effectively lowers blood pressure due to its dual mechanism of action that combines angiotensin receptor blockade with neprilysin inhibition. 1
Mechanism of Action and Blood Pressure Effects
Entresto works through two complementary mechanisms:
Valsartan component: An angiotensin receptor blocker (ARB) that blocks the effects of angiotensin II, causing vasodilation and reduced aldosterone secretion 2
Sacubitril component: A neprilysin inhibitor that prevents the breakdown of natriuretic peptides, which promote vasodilation, natriuresis, and diuresis
The combination of these mechanisms results in significant blood pressure reduction:
- In patients with heart failure and hypertension, Entresto reduced systolic blood pressure by 12.8 ± 21.2 mmHg and diastolic blood pressure by 7.1 ± 16.5 mmHg from baseline 3
- In patients with apparent resistant hypertension, Entresto reduced systolic blood pressure by 4.8-8.8 mmHg more than valsartan alone 4
Clinical Applications
While Entresto is primarily approved for heart failure with reduced ejection fraction (HFrEF), its blood pressure-lowering effects are significant:
- In China and Japan, Entresto has been approved specifically as an antihypertensive agent 3
- In Europe and the USA, it is not currently approved for hypertension treatment but is used for heart failure 3
- In the PARAGON-HF trial, 47.9% of patients with apparent resistant hypertension achieved controlled blood pressure with Entresto compared to 34.3% with valsartan alone 4
Dosing Considerations
- For hypertension treatment in research settings, higher doses (200-400 mg once daily) have been used 1
- Even at lower than target doses, Entresto has demonstrated effective blood pressure reduction in real-world studies 3
Special Populations
- Older patients: May require closer monitoring as they showed higher cumulative hazard of cardiovascular events in real-world studies 3
- Renal dysfunction: Patients with renal dysfunction experienced more adverse events and require careful monitoring 3
Potential Advantages
- Entresto may be particularly beneficial in patients with both hypertension and heart failure 3, 5
- In patients with resistant hypertension and heart failure with preserved ejection fraction, Entresto achieved blood pressure control in 43.6% of cases versus 28.4% with valsartan alone 4
Common Side Effects
- Hypotension is the most common side effect 6
- Careful monitoring is needed, especially when initiating therapy
Conclusion
Entresto represents a novel approach to blood pressure management with its dual mechanism of action. While primarily indicated for heart failure, its blood pressure-lowering effects are well-documented and may offer advantages in specific patient populations, particularly those with comorbid hypertension and heart failure.