Drugs for Heart Failure

HFrEF Pillars: Part 1 - RAAS Rousters & Beta Blockers

• RAAS Inhibitors: Cornerstone for ↓ mortality & remodeling.
  • ACEIs (e.g., Ramipril): ↓ Ang II, ↑ Bradykinin. SEs: Cough, angioedema, hyperK+. ⚠️ Teratogenic.
  • ARBs (e.g., Valsartan): Block AT1. Use if ACEI cough. SEs: HyperK+. ⚠️ Teratogenic.
  • ARNI (Sacubitril/Valsartan): Neprilysin inhibitor + ARB. Superior to ACEI/ARB. Requires 36hr ACEI washout.
• Beta Blockers (BBs): ↓ Mortality, ↓ remodeling, ↓ arrhythmias.
  • Evidence-based: Carvedilol, Metoprolol Succinate, Bisoprolol. 📌 CMB for HFrEF.
  • Mech: ↓ Sympathetic drive, ↓ Renin.
  • Initiate: Low dose, stable patients, titrate slow. SEs: Bradycardia, hypotension.

⭐ ARNI (Sacubitril/Valsartan) is preferred over ACEIs/ARBs in eligible HFrEF patients for further reduction in mortality and hospitalizations.

HFrEF Pillars: Part 2 - Aldo Antagonists & Flozin Friends

1. Aldosterone Antagonists (MRAs)

• Drugs: Spironolactone, Eplerenone.
• Mech: Block aldosterone → ↓Na+/H2O retention, ↓K+ loss, ↓cardiac fibrosis & remodeling.
• Benefits: ↓Mortality, ↓HF hospitalizations.
• SEs: Hyperkalemia (monitor K+!), gynecomastia (Spironolactone > Eplerenone). 📌 Spironolactone: Saves lives, Swells breasts, Spikes K+.
• C/I: K+ >5.0 mEq/L, eGFR <30 mL/min/1.73m².

2. SGLT2 Inhibitors ("Flozins")

• Drugs: Dapagliflozin, Empagliflozin.
• Mech (HF): Multiple benefits: ↓Intraglomerular pressure, ↓Sympathetic tone, ↓Inflammation, ↑Myocardial efficiency. Not just glycosuria.
• Benefits: ↓Mortality, ↓HF hospitalizations (even in non-diabetics).
• SEs: Genital mycotic infections, UTIs, euglycemic DKA (rare), volume depletion.
• Start: eGFR >20-30 mL/min/1.73m².

⭐ SGLT2 inhibitors reduce risk of cardiovascular death and hospitalization for heart failure in HFrEF patients, irrespective of diabetes status.

HF Symptom Relief - Fluid Fighters & Heart Helpers

• Diuretics: Relieve fluid overload.
  • Loop (Furosemide): Potent (TAL; Na-K-2Cl). SE: HypoK, Ototox.
  • Thiazides (HCTZ): Milder (DCT; Na-Cl). SE: HypoK, HyperCa.
  • K+-sparing: Aldo antags (Spironolactone); ENaC blockers (Amiloride).
• Digoxin: ↑Inotropy, ↓Chronotropy.
  • MOA: Na+/K+ ATPase inhib → ↑Ca2+ (contractility); ↑vagal tone (↓HR).
  • Use: Symptomatic HFrEF; AF (RVR). No mortality benefit.
  • Tox: Narrow index (0.5-0.9 ng/mL). Arrhythmias, GI, xanthopsia. 📌 Antidote: DigiFab.
• Hydralazine + ISDN: Vasodilator (arterial + venous).
  • Use: HFrEF (African Americans); ACEi/ARB intolerant. ↓Pre/Afterload.
• Ivabradine: ↓HR.
  • MOA: Selective $I_f$ inhibitor (SA node).
  • Use: HFrEF (LVEF ≤35%, SR, HR ≥70) on max BB / BB C/I.

⭐ Digoxin toxicity classically presents with xanthopsia (yellow vision) and atrial tachycardia with AV block.

HFpEF & Acute HF - Preserved Puzzles & Acute Alerts

HFpEF (Heart Failure with Preserved Ejection Fraction):

• Diastolic dysfunction, LVEF ≥ 50%.
• Focus: Control comorbidities (HTN, DM, AF, obesity).
• Diuretics for volume overload symptoms.
• Key therapies improving outcomes:
  • SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin).
  • MRAs (e.g., spironolactone, eplerenone).
• ARNI (sacubitril/valsartan) shows benefit in some HFpEF subgroups.

Acute Decompensated HF (ADHF):

• Life-threatening; requires rapid assessment & intervention.
• Goals: Improve symptoms (dyspnea), restore perfusion, limit organ damage.
• Initial: IV Loop Diuretics (e.g., Furosemide 40-80 mg IV). Oxygen if SpO₂ < 90%.
• 📌 "POND": Position (upright), Oxygen, Nitrates, Diuretics.
• Therapy guided by hemodynamic profile (see flowchart).

⭐ In HFpEF, SGLT2 inhibitors (dapagliflozin, empagliflozin) are a cornerstone, reducing HF hospitalizations and improving quality of life, irrespective of diabetes status.

High‑Yield Points - ⚡ Biggest Takeaways

• ACE inhibitors/ARBs: First-line in HFrEF, reduce mortality and morbidity.
• Beta-blockers (carvedilol, metoprolol, bisoprolol): Improve survival in chronic stable HFrEF.
• Diuretics: Provide symptomatic relief from congestion; no mortality benefit.
• Aldosterone antagonists (spironolactone): Reduce mortality in HFrEF; risk of hyperkalemia.
• SGLT2 inhibitors (dapagliflozin, empagliflozin): Mortality benefit in HFrEF, even non-diabetics.
• ARNI (Sacubitril/Valsartan): Superior to ACEi/ARB for reducing HFrEF mortality/hospitalization.
• Digoxin: For symptomatic HFrEF with AFib; narrow therapeutic index, monitor toxicity.