From the Guidelines
Guideline-directed medical therapy (GDMT) for heart failure should be initiated promptly in stable patients and carefully escalated during recovery from acute decompensation, prioritizing medications that reduce morbidity and mortality, such as ACE inhibitors, beta-blockers, and SGLT2 inhibitors, as recommended by the most recent guidelines 1.
Key Principles for Initiating and Escalating GDMT
- For compensated heart failure patients, start with an ACE inhibitor (like lisinopril 2.5-5mg daily) or ARB (losartan 25-50mg daily) if ACE inhibitor intolerant, plus a beta-blocker (carvedilol 3.125mg twice daily or metoprolol succinate 12.5-25mg daily) 1.
- Add a mineralocorticoid receptor antagonist (spironolactone 12.5-25mg daily) for patients with LVEF ≤35% 1.
- Uptitrate these medications every 2 weeks as tolerated to target doses, with the goal of achieving optimal dosing to reduce morbidity and mortality 1.
- For LVEF ≤40%, consider adding an SGLT2 inhibitor (dapagliflozin 10mg daily or empagliflozin 10mg daily) regardless of diabetes status, as this has been shown to improve outcomes in heart failure patients 1.
Approach to Acute Decompensated Heart Failure
- Focus initially on diuresis and symptom relief, using loop diuretics as needed, and consider adding an SGLT2 inhibitor to enhance decongestion 1.
- Once the patient is hemodynamically stable with improved symptoms, cautiously reintroduce GDMT starting at low doses (typically 25-50% of usual starting doses), monitoring blood pressure, heart rate, and renal function 1.
- Begin with beta-blockers once euvolemic, followed by ACE inhibitors/ARBs, then add other agents sequentially as tolerated, with the goal of achieving optimal medical therapy to reduce morbidity and mortality 1.
Monitoring and Adjusting GDMT
- Monitor patients closely for signs of decongestion, such as improved symptoms, reduced jugular venous pressure, and increased urine output, and adjust GDMT accordingly 1.
- Use the algorithm outlined in the European Journal of Heart Failure to optimize decongestion in decompensated heart failure, which includes initiating or optimizing GDMT, adjusting loop diuretic doses, and considering the addition of non-loop diuretics or ultrafiltration as needed 1.
From the FDA Drug Label
To reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with reduced left ventricular ejection fraction. The usual recommended starting dose is 2.5 mg (enalapril) or 5 mg (ivabradine) twice daily with food. Doses should be titrated upward, as tolerated, over a period of a few days or weeks. The maximum daily dose administered in clinical trials was 40 mg (enalapril) in divided doses and 7.5 mg (ivabradine) twice daily.
Starting GDMT in Compensated Heart Failure:
- Start with a low dose of 2.5 mg (enalapril) or 5 mg (ivabradine) twice daily.
- Titrate the dose upward every few days or weeks as tolerated.
- Monitor the patient's blood pressure, heart rate, and renal function during titration.
Escalating GDMT in Compensated Heart Failure:
- Increase the dose of enalapril to 5 mg twice daily, then 10 mg twice daily, and up to 20 mg twice daily as needed and tolerated.
- Increase the dose of ivabradine to 7.5 mg twice daily as needed and tolerated.
Starting GDMT in Acute Decompensated Heart Failure:
- Not recommended to start ivabradine in acute decompensated heart failure.
- For enalapril, start with a low dose of 2.5 mg daily under close medical supervision.
- Titrate the dose upward slowly as the patient's condition stabilizes.
Escalating GDMT in Acute Decompensated Heart Failure:
- Once the patient's condition has stabilized, the dose of enalapril can be increased to 2.5 mg twice daily, then 5 mg twice daily, and up to 20 mg twice daily as needed and tolerated.
- Monitor the patient's blood pressure, heart rate, and renal function during titration. 2 3
From the Research
Initiating GDMT in Compensated Heart Failure Patients
- Guideline-directed medical therapy (GDMT) is the cornerstone of pharmacological therapy for patients with heart failure with reduced ejection fraction (HFrEF) 4
- GDMT consists of four main drug classes: renin-angiotensin system inhibitors, evidence-based β-blockers, mineralocorticoid inhibitors, and sodium glucose cotransporter 2 inhibitors 4
- The recommendation for use of GDMT is based on the results of multiple major randomized controlled trials demonstrating improved clinical outcomes in patients with HFrEF who are maintained on this therapy 4
Escalating GDMT in Compensated Heart Failure Patients
- Individualized adjustments in GDMT titration may be necessary based on patient characteristics 5
- Every clinician is responsible for promptly initiating GDMT and titrating it appropriately within the patient's tolerance range 5
- The effect of GDMT is most beneficial when medications from the four main drug classes are used in conjunction 4
Initiating and Escalating GDMT in Acute Decompensated Heart Failure Patients
- Heart failure hospitalization (HFH) represents an important opportunity to titrate GDMT among patients with HFrEF 6
- HFH was positively associated with initiation of angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA) 6
- HFH was also associated with dose escalation of ACE inhibitor/ARB and MRA 6
Challenges and Considerations
- There is an underutilization of GDMT, partially due to lack of awareness of how to safely and effectively initiate and titrate these medications 4
- Many of the recommended GDMT for CHF lack unequivocal evidence of clinical efficacy in patients with diverge etiology of heart failure and concomitant comorbid conditions 7
- De-escalation/discontinuation of GDMT after HFH was associated with increased risk of all-cause mortality 6