What is the appropriate Guideline-Directed Medical Therapy (GDMT) for heart failure in patients with End-Stage Renal Disease (ESRD) on Hemodialysis (HD)?

GDMT for Heart Failure in ESRD on Hemodialysis

Patients with ESRD on hemodialysis should receive guideline-directed medical therapy for heart failure—specifically beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) and ACE inhibitors or ARBs—combined with meticulous volume management through optimized dialysis, as these therapies reduce mortality even in advanced kidney disease, though they are significantly underutilized in this population. 1, 2

Core Pharmacologic Therapy

Beta-Blockers (First Priority)

• Beta-blockers should be initiated and continued in all ESRD patients with HFrEF unless contraindicated, as they provide at least 20% mortality reduction and are safe in this population 3, 1
• Use HF-specific beta-blockers: carvedilol, metoprolol succinate, or bisoprolol 3, 4
• Start at low doses after volume optimization and titrate gradually with close monitoring 5
• Do not discontinue beta-blockers during dialysis or hospitalization unless hemodynamically unstable, as discontinuation increases mortality risk 5

Renin-Angiotensin System Inhibition (Second Priority)

• ACE inhibitors or ARBs should be used in ESRD patients with HF despite concerns about hyperkalemia and renal function, as they reduce mortality by 5-16% 3, 1
• ARNI (sacubitril/valsartan) provides superior mortality benefit (at least 20% reduction) compared to ACE inhibitors and should be preferred when tolerated 5, 3
• Continue these medications even with mild decreases in residual renal function during dialysis, as routine discontinuation worsens outcomes 5
• Monitor potassium closely but do not withhold therapy based solely on ESRD status 1, 2

Mineralocorticoid Receptor Antagonists (Third Priority)

• Aldosterone antagonists (spironolactone or eplerenone) may be used cautiously in ESRD patients with careful potassium and volume monitoring 1, 2
• These provide at least 20% mortality reduction in HFrEF but carry significant hyperkalemia risk in ESRD 3, 1
• Require frequent electrolyte monitoring (at minimum weekly initially) and dose adjustment based on potassium levels 1

SGLT2 Inhibitors (Emerging Priority)

• SGLT2 inhibitors (dapagliflozin or empagliflozin) should be strongly considered as they provide significant mortality benefits in HFrEF 3
• These medications work even in advanced CKD and may have benefits independent of kidney function 5, 3
• Particularly valuable in ESRD as they can be used when blood pressure is low, unlike other GDMT 3

Volume Management: The Critical Foundation

Dialysis Optimization

• Achieving and maintaining euvolemia through optimized dialysis is the cornerstone of HF management in ESRD and must precede or accompany pharmacologic therapy 1, 6
• Assess dry weight frequently and adjust based on clinical examination, not arbitrary targets 6
• Consider more frequent dialysis sessions (>3 times weekly) or longer session duration for patients with persistent volume overload 1, 6
• Avoid excessive ultrafiltration rates that cause intradialytic hypotension, as this may indicate poor cardiac reserve and worse prognosis 2, 6

Diuretic Therapy

• Loop diuretics should be used for residual urine output if present, with doses adjusted to achieve adequate diuresis 5
• Combination diuretic therapy (loop plus thiazide) is reasonable when single-agent diuresis is inadequate 5
• Ultrafiltration during dialysis is preferred over escalating diuretic doses in anuric patients 5

Medication Initiation and Titration Strategy

During Hospitalization

• Continue all existing GDMT during HF hospitalization unless hemodynamically unstable 5
• Initiate GDMT during hospitalization after clinical stability is achieved, as this is a critical window of opportunity 5
• Do not routinely discontinue GDMT for mild decreases in blood pressure or small changes in residual renal function 5
• If GDMT must be temporarily held, reinitiate as soon as possible before discharge 5

Outpatient Titration

• Start with beta-blockers at low doses after volume optimization 5
• Add ACE inhibitor/ARB or preferably ARNI once beta-blocker is stable 3
• Consider SGLT2 inhibitor early, especially if blood pressure limits other medications 3
• Add MRA last, with intensive potassium monitoring 1
• Target doses provide the greatest mortality benefit, though any dose is better than none 3

Monitoring Requirements

• Check electrolytes, BUN, and creatinine during medication titration 5
• Follow-up within 7-14 days after medication adjustments 5
• Assess volume status, blood pressure (supine and upright), and symptoms at each visit 5

Common Pitfalls and How to Avoid Them

Therapeutic Nihilism

• GDMT is dramatically underutilized in ESRD patients with HF despite proven mortality benefits 1, 7, 2
• The exclusion of ESRD patients from clinical trials has created unwarranted hesitancy to use these medications 7
• Most adverse events in HF patients are not attributable to GDMT and should not prevent therapy 3

Premature Discontinuation

• Do not stop GDMT for asymptomatic hypotension or mild hyperkalemia—adjust doses instead 5
• Discontinuing beta-blockers during hospitalization increases mortality risk 5
• Small incremental dose increases with close monitoring are preferable to withholding therapy 3

Volume Mismanagement

• Residual congestion at discharge dramatically increases rehospitalization and death 5
• Dialysis hypotension may indicate inadequate cardiac reserve rather than excessive ultrafiltration 2, 6
• Coordinate closely with nephrology to optimize dialysis prescription alongside GDMT 6

Device Therapy Considerations

• ICD and CRT devices should be considered using the same criteria as in non-ESRD patients 5
• ESRD alone should not preclude device therapy in appropriate candidates 5
• Cardiac resynchronization therapy may provide additional benefit in selected ESRD patients with HF 1

Multidisciplinary Approach

• A coordinated approach between cardiology and nephrology is essential for optimizing both dialysis and pharmacologic strategies 6
• Referral to an HF clinic significantly increases GDMT utilization and appropriate titration 4
• Consider palliative care consultation for patients with refractory symptoms despite optimal therapy 5