Concurrent Use of Coreg and Entresto in Heart Failure
Yes, Coreg (carvedilol) and Entresto (sacubitril/valsartan) should be used together in patients with heart failure with reduced ejection fraction, as this combination represents guideline-directed medical therapy that reduces mortality and hospitalizations. 1
Evidence-Based Rationale for Combination Therapy
Beta-blockers like carvedilol are explicitly recommended as first-line therapy alongside sacubitril/valsartan in patients with symptomatic heart failure and reduced ejection fraction (NYHA class II-IV). 1 The 2022 AHA/ACC/HFSA guidelines clearly list both medications in their evidence-based dosing table for heart failure with reduced ejection fraction, with carvedilol dosed at 3.125 mg twice daily initially, targeting 25-50 mg twice daily, and sacubitril/valsartan starting at 49/51 mg twice daily, targeting 97/103 mg twice daily. 1
The European Society of Cardiology 2016 guidelines similarly position sacubitril/valsartan as a replacement for ACE inhibitors or ARBs, but explicitly state it is "typically used in combination with other heart failure therapies," which includes beta-blockers as foundational treatment. 1
Clinical Implementation Strategy
Sequencing of Therapy
Initiate the ACE inhibitor or ARB first, followed by the beta-blocker, then transition from ACE inhibitor/ARB to sacubitril/valsartan if the patient remains symptomatic. 1 The practical recommendation is to establish beta-blocker therapy early in the disease course for all stable NYHA class II-IV patients. 1
Both medications should be started at low doses and up-titrated slowly to target doses used in clinical trials, checking tolerability, blood pressure, heart rate, and blood chemistry at each step. 1
Monitoring Parameters
Monitor heart rate, blood pressure, clinical status (symptoms, signs of congestion, body weight), renal function, and serum potassium at baseline and 1-2 weeks after initiation or dose increases. 1, 2
A decrease in eGFR >30% or development of hyperkalemia should prompt consideration of dose reduction of sacubitril/valsartan. 2
Check blood chemistry 1-2 weeks after initiation and 1-2 weeks after final dose titration to detect electrolyte abnormalities or renal dysfunction. 1, 2
Real-World Clinical Evidence
Research demonstrates that this combination is both feasible and beneficial in clinical practice. A 2022 study specifically evaluated metoprolol (another beta-blocker) combined with Entresto in congestive heart failure patients, showing improved cardiac function indexes (increased LVEF, decreased LVESD and LVEDD), enhanced vascular endothelial function, and improved coagulation parameters compared to beta-blocker monotherapy. 3
In real-world heart failure clinics, approximately 38% of patients with reduced ejection fraction on optimized guideline-directed medical therapy remain symptomatic and are appropriate candidates for sacubitril/valsartan addition to their existing beta-blocker regimen. 4
Important Caveats
Contraindications and Cautions for Beta-Blockers
Do not initiate beta-blockers in patients with current or recent (within 4 weeks) exacerbation of heart failure requiring hospitalization. 1
Seek specialist advice for NYHA class IV severe heart failure, heart block, heart rate <60 bpm, or persisting signs of congestion (raised jugular venous pressure, ascites, marked peripheral edema). 1
Initiate beta-blockers in stable community patients, not in unstable hospitalized patients with worsening heart failure. 1
Hypotension Risk
Symptomatic hypotension is the most commonly reported side effect of sacubitril/valsartan, occurring more frequently than with other heart failure medications. 5 When combining with carvedilol, which also lowers blood pressure and heart rate, careful monitoring is essential.
If hypotension develops, reduce diuretic doses first if evidence of hypovolemia exists, then consider reducing the sacubitril/valsartan dose. 2
Drug Interactions
The provided evidence focuses on statin interactions with sacubitril/valsartan rather than beta-blocker interactions. No clinically significant drug-drug interactions between carvedilol and sacubitril/valsartan are documented in the guidelines reviewed. 1 The combination is standard practice and explicitly recommended in major heart failure guidelines. 1
Dosing Goals
The objective is to treat patients with both medications at target doses used in clinical trials whenever possible. 1 For carvedilol, this means 25-50 mg twice daily (mean dose achieved in trials: 37 mg total daily), and for sacubitril/valsartan, 97/103 mg twice daily (mean dose achieved: 182/193 mg total daily). 1 However, lower doses of both treatments retain value and should be used if larger doses are not tolerated. 1