Yes, Entresto and Coreg Can Be Used Together
Yes, a patient can and often should be on both Entresto (sacubitril/valsartan) and Coreg (carvedilol) simultaneously for heart failure with reduced ejection fraction (HFrEF). This combination represents guideline-directed medical therapy (GDMT) and is strongly recommended for optimal management of HFrEF.
Guideline-Recommended Combination Therapy
Both medications are core components of GDMT for HFrEF and should be used together in most patients with symptomatic heart failure (NYHA class II-IV) and reduced ejection fraction 1.
The 2022 AHA/ACC/HFSA guidelines explicitly recommend beta-blockers (including carvedilol) alongside ARNIs (Entresto) as foundational therapy for HFrEF 1.
The 2021 ACC Expert Consensus specifically outlines that patients should receive ARNI therapy in addition to beta-blockers, not instead of them 1.
How These Medications Work Together
Entresto (sacubitril/valsartan) blocks the angiotensin II receptor while simultaneously inhibiting neprilysin, which increases beneficial natriuretic peptides 2, 3.
Carvedilol is a beta-blocker that reduces heart rate, decreases myocardial oxygen demand, and blocks harmful neurohormonal activation 1.
These medications have complementary mechanisms of action and target different pathways in the heart failure disease process, making their combination synergistic rather than redundant 1.
Initiation Strategy
Beta-blockers and ARNIs can be started together once the diagnosis of HFrEF has been made 1.
If switching from an ACE inhibitor to Entresto, ensure a 36-hour washout period to avoid the risk of angioedema 1.
Start with low doses of both medications and titrate upward based on tolerance 1:
Important Monitoring Considerations
Monitor blood pressure closely as both medications can cause hypotension, especially when used together 1, 3.
Check renal function and potassium within 2-3 days after initiation and during titration, as Entresto can affect these parameters 1.
Monitor heart rate as carvedilol will reduce heart rate; symptomatic bradycardia may require dose adjustment 1.
If hypotension occurs, consider adjusting diuretic doses first before reducing GDMT medications 1.
Common Pitfalls to Avoid
Do not discontinue the beta-blocker when starting Entresto—this is a common error that deprives patients of proven mortality benefit 1.
Do not use Entresto with an ACE inhibitor—this combination is contraindicated due to increased angioedema risk 1, 4.
Do not combine Entresto with an ARB separately (like losartan)—Entresto already contains valsartan, an ARB component 4.
Avoid excessive caution with blood pressure—asymptomatic hypotension (systolic BP 90-100 mmHg) is often well-tolerated and does not require dose reduction if the patient feels well 1.
Evidence of Benefit
The PARADIGM-HF trial demonstrated that sacubitril/valsartan was superior to enalapril in reducing cardiovascular death and heart failure hospitalization when added to background therapy that included beta-blockers 3.
Patients in PARADIGM-HF were required to be on stable doses of beta-blockers before randomization, confirming the safety and efficacy of this combination 1, 3.