What is the first line treatment for an older adult patient with congestive heart failure (CHF) and reduced ejection fraction, with comorbidities such as hypertension and diabetes?

First-Line Treatment for Heart Failure with Reduced Ejection Fraction (HFrEF)

All patients with HFrEF should be started on four foundational drug classes simultaneously or in rapid sequence within 2-4 weeks: an SGLT2 inhibitor, a beta-blocker, an ARNI (or ACE inhibitor if ARNI unavailable), and a mineralocorticoid receptor antagonist (MRA). 1, 2

Optimal Sequencing Strategy

The most evidence-based approach is a three-step rapid initiation protocol 2:

Step 1 (Day 1-2): Start simultaneously:

• SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) - can be initiated immediately with minimal blood pressure effect and benefits occurring within weeks 1, 2
• Beta-blocker (carvedilol 3.125 mg twice daily, bisoprolol 1.25 mg daily, or metoprolol succinate 12.5-25 mg daily) 3

Step 2 (1-2 weeks later): Add:

• Sacubitril/valsartan (24/26 mg twice daily, titrating to target 97/103 mg twice daily) - preferred over ACE inhibitors for superior mortality reduction 1, 4, 2
• If sacubitril/valsartan unavailable, use ACE inhibitor (enalapril, lisinopril, or ramipril) 3

Step 3 (1-2 weeks later): Add:

• Mineralocorticoid receptor antagonist (spironolactone 12.5-25 mg daily or eplerenone 25 mg daily) 3, 1, 2

Rationale for This Approach

• Low starting doses have substantial therapeutic benefits, and achieving low doses of all four classes takes precedence over up-titration to target doses 2
• Each drug acts independently, so their efficacy does not depend on treatment with the other drugs, allowing flexible sequencing 2
• Drugs reduce morbidity and mortality rapidly, making delayed initiation harmful 2, 5
• SGLT2 inhibitors are started first because they have minimal blood pressure effects, work quickly, and enhance tolerability of subsequent agents 1, 2

Titration Protocol

After establishing all four medications at low doses, uptitrate one medication at a time every 1-2 weeks 1:

Target doses proven in trials:

• Sacubitril/valsartan: 97/103 mg twice daily 1
• Carvedilol: 25-50 mg twice daily 1
• Bisoprolol: 10 mg daily 1
• Metoprolol succinate: 200 mg daily 1
• Spironolactone: 25-50 mg daily 1

Monitoring requirements:

• Check blood pressure, heart rate, renal function (creatinine, eGFR), and electrolytes (potassium) at 1-2 weeks after each dose increment 1
• Modest creatinine increases up to 30% above baseline are acceptable and should not prompt discontinuation 1

Special Considerations for Comorbidities

Hypertension and Diabetes:

• This four-drug regimen simultaneously addresses blood pressure control 6
• SGLT2 inhibitors provide additional glycemic control in diabetic patients 6, 7
• Target blood pressure <130/80 mmHg in high cardiovascular risk patients 6

Older adults (≥65 years):

• Beta-blockers reduce mortality in this population despite not significantly improving quality of life or reducing hospitalizations 3
• Use the same four-drug approach with careful monitoring for hypotension and bradycardia 3
• Start low and go slow with beta-blockers to avoid symptomatic bradycardia 3

COPD:

• Beta-blockers (bisoprolol, carvedilol, metoprolol succinate, nebivolol) can be used if bronchospasm is not present 3, 7
• Do not withhold beta-blockers solely due to COPD diagnosis 3

Critical Contraindications

Never combine:

• ACE inhibitor with ARNI (angioedema risk) 1
• ACE inhibitor + ARB + MRA triple combination (severe hyperkalemia and renal dysfunction risk) 1

Discontinue or avoid:

• NSAIDs - they interfere with RAAS inhibitor efficacy and worsen renal function 1
• Nondihydropyridine calcium channel blockers (diltiazem, verapamil) in decompensated HF 3

Adjunctive Therapy

Loop diuretics:

• Use at the lowest effective dose for symptomatic relief of fluid retention (peripheral edema, orthopnea, pulmonary rales) 6, 1
• Loop diuretics have superior effect profile compared to thiazide diuretics 8
• Critical: Diuretics do not improve prognosis and are purely for symptom control 6

Common Pitfalls to Avoid

• Do not delay initiation of all four foundational therapies - the conventional approach requiring ≥6 months leads to major treatment gaps and preventable deaths 2
• Do not prioritize uptitration over breadth - getting all four drug classes started at low doses is more important than reaching target doses of fewer medications 2
• Do not discontinue medications for modest creatinine elevations - up to 30% increase is acceptable 1
• Do not switch from established beta-blockers - only bisoprolol, carvedilol, metoprolol succinate, and nebivolol have proven mortality benefit; switch patients on other beta-blockers to these agents 3