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.