What are the categories of medicines for treating heart failure?

Categories of Medicines for Treating Heart Failure

The four primary categories of medicines for treating heart failure with reduced ejection fraction (HFrEF) are ACE inhibitors/ARBs/ARNIs, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors. 1

Core Medication Categories for Heart Failure

1. Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors

• ACE Inhibitors: First-line therapy for patients with reduced left ventricular systolic function 1

  • Examples: enalapril, lisinopril, ramipril
  • Mechanism: Block conversion of angiotensin I to angiotensin II
  • Common side effect: Dry cough 2

• Angiotensin Receptor Blockers (ARBs): Alternative for patients who cannot tolerate ACE inhibitors 1

  • Examples: valsartan, losartan, candesartan
  • Mechanism: Block angiotensin II receptors
  • Advantage: Less cough than ACE inhibitors 2

• Angiotensin Receptor-Neprilysin Inhibitors (ARNIs): Newer class combining ARB with neprilysin inhibition 3

  • Example: sacubitril/valsartan
  • Mechanism: Combines ARB effects with inhibition of neprilysin (which degrades natriuretic peptides)
  • Indication: Reduces risk of cardiovascular death and hospitalization for heart failure 3

2. Beta-Adrenergic Blockers

• Beta-Blockers: Reduce sudden death and improve survival in heart failure 1
  • Examples with proven mortality benefit: carvedilol, metoprolol succinate, bisoprolol 1
  • Mechanism: Block harmful effects of the sympathetic nervous system on the heart
  • Class I recommendation with level A evidence 1

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Aldosterone Inhibitors: Block effects of aldosterone 1
  • Examples: spironolactone, eplerenone
  • Mechanism: Block aldosterone receptors, reducing sodium retention and fibrosis
  • Indicated in advanced heart failure (NYHA III-IV) 1
  • Require careful monitoring of potassium and renal function 1

4. SGLT2 Inhibitors

• Sodium-Glucose Cotransporter-2 Inhibitors: Newest class added to guideline-directed medical therapy 1
  • Examples: empagliflozin, dapagliflozin
  • Mechanism: Promote glucose excretion in urine, reduce cardiac workload
  • Effective across the spectrum of heart failure, including HFrEF, HFmrEF, and HFpEF 4

Additional Medication Categories

5. Diuretics

• Loop Diuretics: Essential for symptom management when fluid overload is present 1

  • Examples: furosemide, bumetanide, torsemide
  • Mechanism: Increase urinary sodium and water excretion
  • No proven mortality benefit but improve symptoms and exercise tolerance 1

• Thiazide Diuretics: Often used in combination with loop diuretics for resistant edema 1

  • Examples: hydrochlorothiazide, chlorthalidone
  • May be used as initial therapy in mild heart failure but ineffective if GFR <30 ml/min 1

6. Cardiac Glycosides

• Digitalis: Used for rate control in atrial fibrillation with heart failure 1
  • Example: digoxin
  • Mechanism: Inhibits Na+/K+-ATPase, increases cardiac contractility
  • May improve symptoms but minimal effect on mortality 1

7. Vasodilators

• Nitrates and Hydralazine: Alternative for patients who cannot tolerate RAAS inhibitors 1
  • Mechanism: Direct vasodilation reducing cardiac workload
  • Particularly beneficial in specific populations (e.g., African Americans) 1

8. Ivabradine

• Funny Channel Blockers: Reduces heart rate by inhibiting If channels in the sinoatrial node
  • Primarily reduces hospitalizations rather than mortality 1
  • Used when heart rate remains elevated despite beta-blocker therapy

Medications to Avoid in Heart Failure

• Non-steroidal anti-inflammatory drugs (NSAIDs): Cause sodium and water retention, reduce effectiveness of diuretics and ACE inhibitors 5
• Most calcium channel blockers: Have negative inotropic effects that can worsen heart failure 1, 5
• Most antiarrhythmic drugs: Can have proarrhythmic effects and negative inotropic properties 5
• Thiazolidinediones: Can cause fluid retention and worsen heart failure 5
• Long-term inotropic therapy: May increase mortality except in end-stage disease 1

Treatment Considerations by Heart Failure Type

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Strongest evidence base for treatment
• Quadruple therapy (ARNI/ACEi/ARB + beta-blocker + MRA + SGLT2i) provides comprehensive mortality benefit 1

Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)

• SGLT2i have Class 2a recommendation
• ARNi, ACEi, ARB, MRA, and beta-blockers have Class 2b recommendations 1

Heart Failure with Preserved Ejection Fraction (HFpEF)

• More limited evidence for mortality benefit
• SGLT2i (Class 2a), MRAs (Class 2b), and ARNi (Class 2b) have emerging evidence 1, 4
• Treatment of underlying conditions (especially hypertension) is crucial 1

Common Pitfalls in Heart Failure Medication Management

• Underutilization of evidence-based therapies: All four core medication classes should be considered for eligible patients with HFrEF
• Inadequate dose titration: Medications should be titrated to target doses used in clinical trials when possible
• Inappropriate discontinuation: Medications should generally be continued even when ejection fraction improves 1
• Failure to monitor: Regular assessment of renal function, electrolytes, and blood pressure is essential, especially when initiating or titrating medications
• Polypharmacy issues: Consider drug interactions, especially with potassium-sparing diuretics and RAAS inhibitors

Understanding these medication categories and their appropriate use is essential for optimizing outcomes in patients with heart failure, with the goal of reducing mortality, hospitalizations, and improving quality of life.