What Is Entresto?
Entresto (generic name: sacubitril/valsartan) is a prescription medication used to treat heart failure, specifically heart failure with reduced ejection fraction (HFrEF). Approved by the FDA in 2015, Entresto combines two active components:
- Sacubitril: A neprilysin inhibitor that prevents the breakdown of natriuretic peptides, which help lower blood pressure and reduce strain on the heart.
- Valsartan: An angiotensin receptor blocker (ARB) that relaxes blood vessels, lowers blood pressure, and reduces fluid retention.
Together, these components improve heart function, reduce the risk of hospitalization, and decrease mortality in patients with HFrEF.
Entresto targets two critical pathways in heart failure:
- Neprilysin Inhibition: Sacubitril inhibits neprilysin, an enzyme that degrades beneficial peptides such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). These peptides promote vasodilation, reduce fluid retention, and counteract the harmful effects of the renin-angiotensin-aldosterone system (RAAS).
- Angiotensin Receptor Blockade: Valsartan blocks the effects of angiotensin II, a hormone that causes blood vessel constriction and fluid retention. This blockade reduces blood pressure and eases the workload on the heart.
By addressing both pathways, Entresto provides a dual mechanism to improve cardiovascular outcomes in HFrEF patients.
How Does Entresto Work?
Clinical Evidence Supporting Entresto
The efficacy of Entresto was established in the PARADIGM-HF trial, a landmark study published in the New England Journal of Medicine in 2014.
- Study Design:
- A randomized, double-blind trial involving 8,442 patients with HFrEF (left ventricular ejection fraction ≤40%).
- Compared Entresto (200 mg twice daily) to enalapril (10 mg twice daily), a standard ACE inhibitor.
- 27 month trial
- Key Findings:
- Reduction in Cardiovascular Mortality: The absolute reduction in the risk of cardiovascular death was 4.7% (13.3% for Entresto vs. 17.0% for enalapril).
- Lower Hospitalization Rates: The absolute reduction in the risk of hospitalization for heart failure was 2.8% (12.8% for Entresto vs. 15.6% for enalapril).
- All-Cause Mortality: The absolute reduction in the risk of all-cause mortality was 3.2% (17.0% for Entresto vs. 19.8% for enalapril).
- Long-Term Benefits: Subgroup analyses showed consistent benefits across age, sex, and baseline heart failure severity.
How Does Entresto Lower Absolute Risk?
Entresto’s ability to lower absolute risk stems from its comprehensive effects on heart failure physiology:
- Improved Hemodynamics: By enhancing natriuretic peptide activity, Entresto reduces preload and afterload, improving cardiac output.
- Reduced Neurohormonal Activation: Valsartan’s RAAS inhibition minimizes the harmful effects of angiotensin II, such as fibrosis and fluid overload.
- Prevention of Disease Progression: Entresto’s dual action addresses both systemic and cardiac-specific mechanisms, slowing the progression of heart failure.
Side Effects of Entresto
While Entresto offers significant benefits, it is associated with potential side effects:
- Hypotension: Reported in approximately 18% of patients in clinical trials.
- Hyperkalemia: Elevated potassium levels occurred in 12% of patients.
- Kidney Dysfunction: Worsening renal function was observed in 5% of patients.
- Angioedema: Though rare (0.5%), this potentially life-threatening swelling requires immediate medical attention.
- Cough: Occurred less frequently than with ACE inhibitors but was still reported in some patients.
Who Should Avoid Entresto?
Entresto is contraindicated in:
- Patients with a history of angioedema related to ACE inhibitors or ARBs.
- Patients taking an ACE inhibitor (a 36-hour washout period is required).
- Patients with severe renal impairment or significant hyperkalemia.
- Pregnant women, due to the risk of fetal harm.
Natural Treatment Strategies
At Natural Heart Doctor, our methods can help people with heart failure live better and live longer. There are CAUSES to congestive heart failure, and we help FIND and REVERSE them.
Let’s work together on your 100 Year Heart.
