🫁 Guideline-Directed Medical Therapy 4-Pillar Simulator

Sacubitril/Valsartan Replacing ACEi/ARB

PARADIGM-HF showed ARNI beats enalapril for mortality and hospitalization.

• PARADIGM-HF: Trial (placeholder summary)
• 20%: Mortality RRR (placeholder summary)
• 97/103mg BID: Target dose (placeholder summary)
• 36h ACEi washout: Key caution (placeholder summary)

Mechanism and titration

Placeholder: neprilysin inhibition plus ARB blockade.

Placeholder: start low, uptitrate every 2-4 weeks.

Evidence-Based Beta-Blockade in HFrEF

Carvedilol, metoprolol succinate, bisoprolol reduce sudden death risk.

• 3 approved: Agents (placeholder summary)
• 35%: Mortality RRR (placeholder summary)
• Every 2 weeks: Titration (placeholder summary)
• Avoid in decompensation: Caution (placeholder summary)

Mechanism and titration

Placeholder: blunts catecholamine-driven remodeling.

Placeholder: initiate once euvolemic and stable.

Spironolactone and Mineralocorticoid Blockade

RALES and EMPHASIS-HF confirmed mortality benefit of MRAs.

• RALES/EMPHASIS: Trial (placeholder summary)
• 30%: Mortality RRR (placeholder summary)
• K+ and eGFR: Monitoring (placeholder summary)
• Hyperkalemia: Risk (placeholder summary)

Mechanism and titration

Placeholder: blocks aldosterone-driven fibrosis.

Placeholder: check potassium 1 week after starting.

SGLT2 Inhibitors Across the Ejection Fraction Spectrum

Dapagliflozin and empagliflozin help regardless of diabetes.

• DAPA-HF/EMPEROR: Trials (placeholder summary)
• 25%: Mortality RRR (placeholder summary)
• Weeks: Onset (placeholder summary)
• Genital infection: Risk (placeholder summary)

Mechanism and titration

Placeholder: natriuresis and metabolic effects combine.

Placeholder: fixed dose, no titration needed.

Four Pillars Stacked — Compounding Mortality Reduction

Together the four drug classes yield very large absolute benefit.

• ~73%: Combined RRR (placeholder summary)
• ~9: NNT (2yr) (placeholder summary)
• <4 weeks goal: Time to all 4 (placeholder summary)
• Clinical inertia: Barrier (placeholder summary)

Why sequencing speed matters

Placeholder: rapid stacking beats slow sequential titration.

Placeholder: start all 4 pillars early, then uptitrate.