What are the initial doses of Guideline-Directed Medical Therapy (GDMT)?

Initial Doses of Guideline-Directed Medical Therapy (GDMT) for Heart Failure

GDMT for heart failure with reduced ejection fraction (HFrEF) should be initiated at low doses and gradually titrated to target doses to reduce mortality and hospitalizations, with medications started simultaneously or sequentially based on patient factors. 1, 2

Core Medication Classes and Initial Doses

Beta-Blockers

• Start with low doses and gradually increase to target doses 1:
  • Carvedilol: Start at 3.125 mg twice daily (target: 25 mg twice daily) 1, 2
  • Metoprolol succinate: Start at 12.5-25 mg once daily (target: 200 mg once daily) 1, 2
  • Bisoprolol: Start at 1.25 mg once daily (target: 10 mg once daily) 1, 2

ACE Inhibitors

• Start at low doses and titrate upward 1:
  • Lisinopril: Start at 2.5-5 mg once daily (target: 20 mg once daily) 1, 3
  • Enalapril: Start at 2.5 mg twice daily (target: 10 mg twice daily) 1
  • Captopril: Start at 6.25 mg three times daily (target: 50 mg three times daily) 1

Angiotensin Receptor Blockers (ARBs)

• For patients intolerant to ACE inhibitors 1:
  • Valsartan: Start at 40 mg twice daily (target: 160 mg twice daily) 1
  • Candesartan: Start at 4-8 mg once daily (target: 32 mg once daily) 1
  • Losartan: Start at 25-50 mg once daily (target: 100 mg once daily) 1

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

• Sacubitril/valsartan: Start at 24/26 mg twice daily (target: 97/103 mg twice daily) 1, 2
• Lower starting dose (24/26 mg twice daily) for patients not currently taking ACE inhibitor/ARB or on low doses 1

Mineralocorticoid Receptor Antagonists (MRAs)

• Spironolactone: Start at 12.5-25 mg once daily (target: 25-50 mg once daily) 1, 2
• Eplerenone: Start at 25 mg once daily (target: 50 mg once daily) 1, 2

SGLT2 Inhibitors

• Dapagliflozin: Start at 10 mg once daily (maintenance: 10 mg once daily) 1, 2
• Empagliflozin: Start at 10 mg once daily (maintenance: 10 mg once daily) 1, 2

Implementation Strategies

Initiation Approach

• GDMT medications can be started simultaneously at initial low doses or sequentially, with the sequence guided by clinical factors 1
• Starting multiple medications at once has been shown to improve outcomes without significant increase in adverse events 1
• Medication doses should be increased to target as tolerated, with adjustments no more frequently than every 2 weeks 1

Monitoring and Titration

• Monitor vital signs closely before and during uptitration, including postural changes in blood pressure or heart rate 1
• Check renal function and electrolytes for rising creatinine and hyperkalemia, recognizing that an initial rise in creatinine may be expected 1
• Uptitrate in small increments to the recommended target dose or highest tolerated dose 1
• Certain patients (elderly, those with chronic kidney disease) may require more frequent visits and laboratory monitoring during dose titration 1

Special Considerations

Hypotension Management

• For symptomatic hypotension, evaluate for over-diuresis, non-CV drugs with hemodynamic effects, or autonomic dysfunction before reducing GDMT doses 1
• For persistent hypotension, use best-tolerated doses of GDMT, accepting that lower doses may be necessary 1

Renal Function

• In patients with renal insufficiency (GFR 10-30 mL/min), reduce initial doses of ACE inhibitors by half 3
• For patients with creatinine clearance <30 mL/min, use less than target doses of ACE inhibitors/ARBs and consider discontinuing aldosterone antagonists if serum potassium >5.0 mEq/L 1

Common Pitfalls to Avoid

• Failure to initiate GDMT early - delayed initiation is associated with never starting these life-saving medications 1, 4
• Underutilization of target doses - studies show many patients remain on suboptimal doses despite evidence supporting dose-response relationships 1, 5
• Stopping medications due to mild, transient side effects that often resolve within days of dose changes 1
• Failing to continue GDMT in patients whose EF improves to >40% (HFimpEF) 1, 2

Practical Tips

• Educate patients about expected benefits of achieving GDMT, including improved survival and quality of life 1
• Discourage sudden discontinuation of GDMT medications without discussion with managing clinicians 1
• Consider temporary adjustments in GDMT dosages during acute non-cardiac illnesses 1
• For patients with difficulty achieving target doses, referral to a heart failure specialist may be beneficial 1, 6