In a patient with ischemic cardiomyopathy and left ventricular ejection fraction 29% who is symptomatic and hypertensive (160/100 mmHg) while taking sacubitril/valsartan 50 mg twice daily (angiotensin receptor‑neprilysin inhibitor), carvedilol 3.25 mg twice daily (beta‑blocker), furosemide 5 mg daily (loop diuretic), metformin, and dapagliflozin 10 mg (SGLT2 inhibitor), what are the recommended next steps in management?

Management of Hypertensive HFrEF Patient on Suboptimal GDMT

Your patient requires immediate aggressive uptitration of all four foundational medication classes, with the addition of a mineralocorticoid receptor antagonist (MRA) being the single most critical missing component that provides at least 20% mortality reduction. 1

Current Medication Assessment

Your patient is significantly under-treated on three critical fronts:

• ARNI dose is severely suboptimal: Sacubitril/valsartan 50 mg twice daily is only 51% of the target dose (97/103 mg twice daily), forfeiting substantial mortality benefit that accrues at target dosing 1, 2
• Beta-blocker dose is critically low: Carvedilol 3.25 mg twice daily is only 13% of the target dose (25-50 mg twice daily for patients >85 kg), providing minimal mortality protection 1, 2
• MRA is completely absent: This patient has no mineralocorticoid receptor antagonist despite LVEF 29%, which represents a missed opportunity for ≥20% mortality reduction and sudden cardiac death prevention 1, 2
• Diuretic dose appears inadequate: Furosemide 5 mg daily is an unusually low dose that likely fails to achieve euvolemia 1

Immediate Action Plan

Step 1: Add Spironolactone Immediately (Highest Priority)

Start spironolactone 25 mg once daily today. 1, 2 This is the single most impactful intervention because:

• MRAs provide at least 20% mortality reduction when added to ACE-I/ARNI and beta-blocker therapy 1, 2
• MRAs have minimal blood pressure effects, making them ideal for patients with hypertension who need BP reduction 2
• The combination of ARNI + MRA is safer than ACE-I + MRA regarding hyperkalemia risk 2
• Target dose is 50 mg daily after 8 weeks if tolerated 2

Monitoring requirements: Check potassium and creatinine at 1 week, then 4 weeks, then 8 weeks after initiation 2

Step 2: Optimize Diuretic for Volume Status

Increase furosemide to 20-40 mg once daily (or equivalent dose based on clinical assessment of congestion). 1

• Assess for signs of congestion: peripheral edema, jugular venous distension, pulmonary rales 1
• The goal is euvolemia (no edema, no orthopnea, no JVD), then use the lowest dose that maintains this state 2
• If BP remains elevated after achieving euvolemia, this supports further GDMT uptitration rather than additional diuretic 1

Step 3: Aggressive ARNI Uptitration (Week 2)

Increase sacubitril/valsartan from 50 mg to 97 mg twice daily at week 2. 1, 2

• The BP of 160/100 mmHg is not a contraindication—it is an indication for uptitration 2
• ARNI provides at least 20% mortality reduction superior to ACE inhibitors, but only at target doses 1, 2
• The current dose of 50 mg BID leaves substantial mortality benefit on the table 3, 4
• Monitor BP and renal function 1-2 weeks after dose increase 2

Step 4: Beta-Blocker Optimization (Week 4)

Increase carvedilol from 3.25 mg to 6.25 mg twice daily at week 4, then continue uptitration every 2 weeks toward target dose of 25-50 mg twice daily. 1, 2

• Beta-blockers provide 34% mortality reduction—the highest relative risk reduction among the four medication classes 2
• Uptitration should proceed if resting heart rate ≥70 bpm and systolic BP >80 mmHg 1, 2
• The current dose of 3.25 mg BID is a "starter dose" that provides minimal therapeutic benefit 1

Titration schedule: 3.25 mg BID → 6.25 mg BID (week 4) → 12.5 mg BID (week 6) → 25 mg BID (week 8) → 50 mg BID if >85 kg (week 10) 1, 2

Managing the Hypertension During Uptitration

The elevated BP (160/100 mmHg) is actually facilitating safe GDMT optimization, not hindering it. 2

• Never delay uptitration due to "adequate" blood pressure—this patient needs maximal GDMT regardless of baseline BP 2
• GDMT medications maintain efficacy and safety even in patients with baseline SBP <110 mmHg 2
• The BP will likely normalize as cardiac output improves with effective heart failure therapy 5
• Asymptomatic hypotension down to SBP ≈80 mmHg with adequate perfusion does not require dose reduction 2

Diabetes Management Considerations

Your patient is already on optimal diabetes therapy for HFrEF:

• Continue dapagliflozin 10 mg daily—this is the fourth foundational medication class providing cardiovascular death and HF hospitalization reduction regardless of diabetes status 1, 2
• Continue metformin—this is the first-line oral hypoglycemic drug recommended by ESC 1
• SGLT2 inhibitors have minimal BP effects, making them ideal for early initiation 2

Critical Contraindications to Avoid

• Never combine ACE inhibitor with ARNI (angioedema risk) 2
• Never use triple combination of ACE inhibitor + ARB + MRA (hyperkalemia and renal dysfunction) 2
• Avoid non-evidence-based beta-blockers (diltiazem, verapamil) which increase worsening HF risk 2
• Do not discontinue GDMT for asymptomatic hypotension—adverse events occur in 75-85% of HFrEF patients regardless of treatment 2

Expected Outcomes with Optimal Therapy

When all four medication classes are optimized to target doses, your patient can expect:

• 61% reduction in all-cause mortality (HR 0.39,95% CI 0.32-0.49) compared to no disease-modifying therapy 2
• Approximately 5.3 additional life-years compared to no treatment 2
• Reduction in HF hospitalizations within 4 months of treatment 4
• Symptom improvement (fatigue, dyspnea) typically within 3-6 months 1, 4

Common Pitfalls to Avoid

• Accepting suboptimal doses due to unfounded BP concerns—clinical trials demonstrated benefits at target doses, not low doses 2, 3
• Delaying MRA initiation due to hyperkalemia concerns—use potassium binders (patiromer) rather than discontinuing life-saving medications 2
• Stopping medications for asymptomatic hypotension—GDMT maintains efficacy even with SBP <110 mmHg 2
• Inadequate monitoring—check potassium and creatinine 1-2 weeks after each dose increment 2
• Using non-evidence-based beta-blockers—only carvedilol, metoprolol succinate, and bisoprolol reduce mortality 1, 2

Monitoring Schedule

Timepoint	Intervention	Labs	BP/HR Target
Today	Add spironolactone 25 mg daily; Increase furosemide to 20-40 mg daily	Baseline K+, Cr	Any BP acceptable
Week 1	—	K+, Cr	—
Week 2	Increase ARNI to 97 mg BID	K+, Cr	SBP >80 mmHg
Week 4	Increase carvedilol to 6.25 mg BID; Increase spironolactone to 50 mg daily if K+ <5.0	K+, Cr	HR ≥70 bpm, SBP >80 mmHg
Week 6	Increase carvedilol to 12.5 mg BID	K+, Cr	HR ≥70 bpm, SBP >80 mmHg
Week 8	Increase carvedilol to 25 mg BID	K+, Cr	HR ≥70 bpm, SBP >80 mmHg

When to Seek Specialist Input

• Persistent hyperkalemia >5.5 mEq/L despite potassium binders 2
• Symptomatic hypotension (SBP <80 mmHg with dizziness, confusion, or altered mental status) 2
• Worsening renal function (creatinine increase >30% above baseline) 2
• Inability to achieve at least 50% of target doses of all four medication classes 2