What is the next medication for a patient with cardiomyopathy and hypertension, currently on amlodipine 10 mg, high-dose Entresto (sacubitril/valsartan), carvedilol 25 mg twice daily (BID), and Lasix (furosemide)?

From the Guidelines

For a patient with cardiomyopathy who remains hypertensive despite being on amlodipine 10 mg, high-dose Entresto, carvedilol 25 mg BID, and furosemide, the next medication to consider adding would be spironolactone, starting at 25 mg daily, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. This decision is based on the patient's current medication regimen and the need for additional blood pressure control, as well as the potential mortality benefits of spironolactone in patients with heart failure. The 2022 guideline suggests that spironolactone can be started at a dose of 12.5-25 mg once daily, with a target dose of 25-50 mg once daily 1. It is essential to monitor the patient's potassium and renal function before initiating spironolactone and to follow up with monitoring within 1-2 weeks of starting therapy. If the patient cannot tolerate spironolactone due to side effects, eplerenone could be considered as an alternative, starting at 25 mg daily, as suggested by the 2021 ACC expert consensus decision pathway for optimization of heart failure treatment 1. Other options, such as adding a thiazide diuretic like chlorthalidone or considering hydralazine with isosorbide dinitrate, may also be considered if aldosterone antagonists are contraindicated or ineffective. Key considerations in the management of heart failure with reduced ejection fraction, as outlined in the 2021 update to the ACC expert consensus decision pathway, include the use of guideline-directed medical therapy, including ACE inhibitors, ARBs, ARNIs, beta-blockers, and SGLT2 inhibitors, as well as the importance of titrating medications to maximally tolerated doses 1. In this case, the addition of spironolactone is a reasonable next step in the patient's management, given the potential benefits of this medication in patients with heart failure and the need for additional blood pressure control.

From the FDA Drug Label

In patients with serum potassium ≤ 5.0 mEq/L and eGFR > 50 mL/min/1.73 m^2, initiate treatment at 25 mg once daily. The recommended initial daily dose is 25 mg to 100 mg of spironolactone tablets administered in either single or divided doses is recommended.

The next medication to consider for this patient with cardiomyopathy and elevated blood pressure, already on amlodipine, high-dose Entresto, carvedilol, and Lasix, could be spironolactone at an initial dose of 25 mg once daily 2.

• Key considerations: serum potassium levels and eGFR should be evaluated before initiating spironolactone therapy.
• Monitoring: regular monitoring of serum potassium levels is crucial to avoid hyperkalemia.

From the Research

Patient's Current Medication and Condition

• The patient is currently taking amlodipine 10 mg, high dose Entresto, carvedilol 25 BID, and Lasix.
• Despite this medication regimen, the patient's blood pressure remains elevated.
• The patient has cardiomyopathy, which is a disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body.

Potential Next Medication

• Considering the patient's condition and current medication, sacubitril/valsartan could be a potential next medication to consider, as it has been shown to be effective in treating heart failure with reduced ejection fraction (HFrEF) 3, 4, 5, 6.
• Sacubitril/valsartan is a dual neprilysin and angiotensin receptor inhibitor that has been demonstrated to reduce mortality and hospitalization rates in patients with HFrEF 4, 5.
• The patient's cardiomyopathy and elevated blood pressure despite current medication suggest that sacubitril/valsartan could be a beneficial addition to their treatment regimen.

Rationale for Sacubitril/Valsartan

• The PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced mortality and hospitalization rates in patients with HFrEF compared to enalapril 4, 5.
• The PARAGON-HF trial showed that sacubitril/valsartan was efficacious in patients with mildly abnormal left ventricular ejection fraction (LVEF) 5.
• Studies have also shown that sacubitril/valsartan improves patient-reported health outcomes, such as Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores, and reduces amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations 6.