What is the best choice of antihypertensive (anti-hypertensive) medication for a patient with Heart Failure with preserved Ejection Fraction (HFpEF), a heart rate in the 60s (bradycardia), fluid overload, and impaired renal function (elevated creatinine)?

Antihypertensive Selection for HFpEF Patient with Bradycardia, Fluid Overload, and Renal Impairment

For a patient with HFpEF, heart rate in the 60s, fluid overload, and impaired renal function (creatinine 250), a loop diuretic should be the first-line antihypertensive therapy, with cautious addition of an ARB if blood pressure remains uncontrolled after diuresis. 1

Initial Management: Addressing Fluid Overload

• Loop diuretics (furosemide, torsemide, or bumetanide) are the cornerstone of treatment for patients with HFpEF who have evidence of fluid retention, as they are the only drugs that can adequately control fluid retention in heart failure 1
• For patients with significant renal impairment (creatinine 250), loop diuretics are preferred over thiazides due to their effectiveness even at lower GFR levels 1
• Start with a lower dose and titrate based on response, with close monitoring of renal function and electrolytes 1, 2
• Torsemide may be preferred over furosemide in this setting due to its longer duration of action (12-16 hours vs. 6-8 hours) and potentially better bioavailability in patients with renal impairment 1

Secondary Antihypertensive Options

Preferred Agents:

• ARBs may be considered after achieving euvolemia to reduce heart failure hospitalizations and further control blood pressure 1

  • Candesartan specifically has shown modest benefit in HFpEF for reducing hospitalizations 1, 3
  • Start with low doses and titrate slowly while monitoring renal function and potassium levels 2

• SGLT2 inhibitors are recommended for patients with HFpEF to improve outcomes, with modest BP-lowering properties 1, 4

  • These have shown benefit in reducing cardiovascular death and heart failure hospitalizations in HFpEF patients, including those with CKD stage 3-4 (eGFR >20 ml/min/1.73m²) 2, 4

Agents to Use with Caution:

• Mineralocorticoid receptor antagonists (MRAs) like spironolactone may be considered in selected patients with HFpEF to reduce hospitalizations 1

  • However, with a creatinine of 250, the risk of hyperkalemia is significant, requiring very careful monitoring if used 1, 2

• ACE inhibitors should be used with extreme caution given the significant renal impairment and risk of further worsening kidney function 5, 2

Agents to Avoid:

• Beta-blockers should be avoided or used with extreme caution given the patient's existing bradycardia (HR in 60s) 1

  • While they may help with hypertension control, they could worsen bradycardia and potentially reduce cardiac output 1

• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) should be avoided in this patient due to their negative chronotropic effects that could worsen bradycardia 1

Management Algorithm

1. First step: Optimize volume status with appropriate loop diuretic therapy

   • Start with lower doses (e.g., furosemide 20-40mg daily or torsemide 10-20mg daily) 1
   • Titrate based on clinical response (improvement in fluid overload) and renal function 1

2. Second step: If blood pressure remains elevated after achieving euvolemia:

   • Add low-dose ARB (e.g., candesartan starting at 4mg daily) with careful monitoring of renal function and potassium 1
   • Consider SGLT2 inhibitor if diabetes is present or if further BP control is needed 1, 4

3. Third step: If BP remains uncontrolled:

   • Consider adding a dihydropyridine calcium channel blocker (amlodipine) which has been shown to be safe in HFpEF 1

4. Monitoring requirements:

   • Frequent assessment of renal function and electrolytes (especially potassium)
   • Daily weight measurements to assess fluid status
   • Blood pressure and heart rate monitoring 2

Special Considerations

• The target systolic BP for patients with HFpEF and CKD should be 130-139 mmHg, with individualized treatment based on tolerability and impact on renal function 1
• For patients with eGFR <30 ml/min/1.73m² (as in this case), BP targets should be individualized 1
• Combination of multiple renin-angiotensin system blockers (ACE inhibitors, ARBs, or direct renin inhibitors) should be avoided due to increased risk of hyperkalemia and worsening renal function 1, 2