From the Guidelines
Entresto is not primarily used for coronary artery disease (CAD), but rather for heart failure with reduced ejection fraction (HFrEF), as it has been shown to reduce the risk of heart failure hospitalization and death in these patients 1, 2, 3, 4.
Key Points to Consider
- Entresto, which contains sacubitril and valsartan, is specifically approved for HFrEF, working by enhancing beneficial neurohormonal systems while inhibiting the harmful renin-angiotensin-aldosterone system, helping to reduce the workload on the failing heart.
- While patients with CAD often develop heart failure as a complication, Entresto targets the heart failure component rather than the underlying coronary artery disease itself.
- For CAD management, medications typically include antiplatelet agents (like aspirin), statins, beta-blockers, and ACE inhibitors/ARBs.
- If a patient has both CAD and heart failure with reduced ejection fraction, Entresto might be part of their treatment regimen, but it would be addressing the heart failure aspect of their condition rather than directly treating the coronary artery disease.
Clinical Guidelines and Recommendations
- The 2024 ESC guidelines for the management of chronic coronary syndromes recommend sacubitril/valsartan as a replacement for an ACE-I or ARB in CCS patients with HFrEF to reduce the risk of heart failure hospitalization and death 1, 2.
- The guidelines also recommend that CCS patients with heart failure be enrolled in a multidisciplinary heart failure management programme to reduce the risk of heart failure hospitalization and to improve survival 1, 2, 3.
Evidence-Based Decision Making
- The use of Entresto in patients with HFrEF has been supported by clinical trials, including a large randomized clinical trial that compared an ARNI (valsartan/sacubitril) with an ACE inhibitor (enalapril) in symptomatic patients with HFrEF, showing a significant reduction in the composite endpoint of cardiovascular death or heart failure hospitalization 4.
- Additional clinical trial evidence, meta-analyses, and observational clinical effectiveness studies have further supported the use of valsartan/sacubitril in replacement of ACE inhibitor or ARB therapy to reduce mortality and morbidity 4.
From the Research
Entresto and CAD
- Entresto, also known as sacubitril/valsartan, is a medication primarily used to treat heart failure with reduced ejection fraction (HFrEF) 5, 6, 7, 8.
- The medication works by inhibiting the angiotensin receptor and neprilysin, which helps to reduce cardiovascular mortality and hospitalization due to heart failure 6, 8.
- While Entresto is not directly indicated for the treatment of coronary artery disease (CAD), it has been shown to reduce the risk of coronary outcomes, including cardiovascular death, non-fatal myocardial infarction, angina hospitalization, and coronary revascularization 9.
- The PARADIGM-HF trial demonstrated that sacubitril/valsartan reduced the risk of the primary composite endpoint of cardiovascular death or heart failure hospitalization, as well as a broader composite including myocardial infarction, stroke, and resuscitated sudden death 9.
Mechanism of Action
- Entresto's dual mechanism of action, combining angiotensin receptor blockade and neprilysin inhibition, provides a unique approach to treating heart failure 7, 8.
- The neprilysin inhibition component of Entresto helps to increase the levels of natriuretic peptides, which have beneficial effects on the heart and blood vessels 8.
- The angiotensin receptor blockade component of Entresto helps to reduce blood pressure and decrease the workload on the heart 7, 8.
Clinical Benefits
- Entresto has been shown to provide significant clinical benefits in patients with HFrEF, including reduced mortality and hospitalization due to heart failure 6, 8.
- The medication has also been shown to improve cardiac remodeling and quality of life in patients with HFrEF 8.
- Entresto has a demonstrated safety and tolerability profile in various patient subpopulations, including those with type 2 diabetes mellitus 8.