What is the optimal management for a 42‑year‑old woman with mildly reduced left ventricular ejection fraction (41 %) and uncontrolled hypertension (180/104 mm Hg) despite losartan therapy?

Optimal Management of Uncontrolled Hypertension in HFrEF

This patient requires immediate intensification of her heart failure regimen with quadruple guideline-directed medical therapy (GDMT), not simply adding another antihypertensive agent. Her mildly reduced ejection fraction of 41% qualifies as heart failure with reduced ejection fraction (HFrEF), and her severely elevated blood pressure of 180/104 mm Hg on losartan alone indicates both inadequate hypertension control and suboptimal heart failure management. 1

Immediate Treatment Strategy

Initiate all four foundational medication classes simultaneously as soon as possible:

1. Replace Losartan with Sacubitril/Valsartan (ARNI)

• Switch from losartan to sacubitril/valsartan 24/26 mg twice daily after discontinuing losartan (no washout period required when switching from an ARB). 2
• Sacubitril/valsartan provides at least 20% mortality reduction superior to ACE inhibitors or ARBs and will provide better blood pressure control than losartan alone. 1, 2
• Titrate to target dose of 97/103 mg twice daily over 4-8 weeks using 2-week intervals. 2
• Her blood pressure of 180/104 mm Hg is well above the 100 mm Hg threshold, making her an ideal candidate for immediate initiation. 2

2. Add an SGLT2 Inhibitor Immediately

• Start dapagliflozin 10 mg once daily or empagliflozin 10 mg once daily. 1
• SGLT2 inhibitors reduce cardiovascular death and heart failure hospitalization regardless of diabetes status, with minimal blood pressure effect (only -1.50 mm Hg in patients with baseline SBP 95-110 mm Hg). 1
• No dose titration is required; maximal benefit occurs at the starting dose. 1
• Benefits occur within weeks of initiation. 1

3. Add a Mineralocorticoid Receptor Antagonist

• Start spironolactone 12.5-25 mg once daily. 1
• MRAs provide at least 20% mortality reduction and reduce sudden cardiac death, with minimal blood pressure effect. 1
• Titrate to target dose of 50 mg daily at 8 weeks if tolerated. 1
• Requires monitoring of renal function and serum potassium (ensure potassium <5.0 mEq/L before initiating). 1

4. Add an Evidence-Based Beta-Blocker

• Start carvedilol 3.125 mg twice daily, metoprolol succinate 12.5-25 mg once daily, or bisoprolol 1.25 mg once daily. 1
• Beta-blockers provide 34% mortality reduction, the highest relative risk reduction among the four medication classes. 1
• Titrate every 2 weeks toward target doses: carvedilol 25-50 mg twice daily, metoprolol succinate 200 mg daily, or bisoprolol 10 mg daily. 1
• Her elevated blood pressure of 180/104 mm Hg provides ample room for beta-blocker titration. 1

Sequencing and Titration Protocol

Start SGLT2 inhibitor and MRA first since they have minimal blood pressure effects, then add beta-blocker, then uptitrate sacubitril/valsartan. 1

• Week 0: Discontinue losartan, start sacubitril/valsartan 24/26 mg BID + dapagliflozin 10 mg daily + spironolactone 12.5-25 mg daily. 1, 2
• Week 2: Add beta-blocker at starting dose; check blood pressure, renal function, and potassium. 1
• Week 4: Increase sacubitril/valsartan to 49/51 mg BID if tolerated; uptitrate beta-blocker. 2
• Week 6-8: Continue uptitrating sacubitril/valsartan to target 97/103 mg BID and beta-blocker to target dose. 1, 2
• Week 8: Increase spironolactone to 50 mg daily if tolerated. 1

Blood Pressure Management During Optimization

• Never discontinue or reduce GDMT for asymptomatic hypotension with adequate perfusion. 1
• GDMT medications maintain efficacy and safety even in patients with baseline systolic blood pressure <110 mm Hg. 1
• Her current blood pressure of 180/104 mm Hg provides substantial margin for aggressive GDMT optimization. 1
• If symptomatic hypotension develops during titration, address reversible non-HF causes first (dehydration, infection) before reducing GDMT doses. 1

Monitoring Requirements

• Check blood pressure, renal function (creatinine, eGFR), and serum potassium at 1-2 weeks after each dose increment. 1
• Modest increases in creatinine (up to 30% above baseline) are acceptable and should not prompt discontinuation. 1
• If potassium rises above 5.0 mEq/L, consider potassium binders (patiromer) rather than discontinuing life-saving MRA therapy. 1
• More frequent monitoring is warranted given her hypertension and need for rapid titration. 1

Expected Outcomes

This quadruple therapy regimen provides approximately 61% reduction in all-cause mortality (HR 0.39,95% CI 0.32-0.49) and adds approximately 5.3 life-years compared to no treatment. 1

• Sacubitril/valsartan alone reduces cardiovascular death or heart failure hospitalization by 20% compared to ACE inhibitors. 2
• The combination of all four medication classes will provide superior blood pressure control compared to losartan monotherapy while simultaneously addressing her heart failure. 1

Critical Pitfalls to Avoid

• Do not simply add another antihypertensive agent to losartan—this patient needs comprehensive HFrEF management, not just blood pressure control. 1
• Do not delay initiation of all four medication classes—accepting suboptimal therapy reduces mortality benefits. 1
• Do not accept low doses due to unfounded blood pressure concerns—clinical trials demonstrated benefits at target doses, not low doses. 1
• Do not use non-evidence-based beta-blockers (atenolol, labetalol) or calcium channel blockers (diltiazem, verapamil), which are contraindicated in HFrEF. 1
• Do not combine ACE inhibitor with ARNI or use triple combination of ACE inhibitor + ARB + MRA due to hyperkalemia and angioedema risk. 1