Guideline-Directed Medical Therapy (GDMT) for HFrEF: The Four Pillars<\/p>\n
\u2022\u2060 \u2060All symptomatic HFrEF patients should receive the four foundational therapies as early as possible, starting with low doses and uptitrating in parallel to the target or maximally tolerated dose.<\/p>\n
1.\u2060 \u2060Renin\u2013Angiotensin System Inhibitor \/ ARNI<\/p>\n
\u2022\u2060 \u2060Sacubitril\/valsartan : 24\/26mg (50mg tab)or 49\/51mg(100mg tab) bid \u2192 97\/103 mg (200mg tab)bid (preferred).
\n\u2022\u2060 \u2060If ARNI is not used:
\n* Candesartan: 4 \u2192 32 mg daily.
\n* Losartan: 50 \u2192 150 mg daily.
\n* Valsartan: 40 mg bid \u2192 160 mg bid (unlike its once-daily use in hypertension).
\n\u2022\u2060 \u2060Increase dose every \u22652 weeks; monitor blood pressure, renal function, and electrolytes.
\n\u2022\u2060 \u2060Allow a 36-hour washout when switching from an ACE inhibitor to ARNI.<\/p>\n
2.\u2060 \u2060Evidence-Based Beta-Blockers<\/p>\n
\u2022\u2060 \u2060Bisoprolol: 1.25 \u2192 10 mg daily.
\n\u2022\u2060 \u2060Carvedilol: 3.125 mg bid \u2192 25 mg bid (50 mg bid if >85 kg).
\n\u2022\u2060 \u2060Nebivolol: 1.25 \u2192 10 mg daily.
\n\u2022\u2060 \u2060Start only in stable, euvolemic patients and uptitrate every \u22652 weeks.<\/p>\n
3.\u2060 \u2060Mineralocorticoid Receptor Antagonists (MRA)<\/p>\n
\u2022\u2060 \u2060Spironolactone: 25 \u2192 50 mg daily.
\n\u2022\u2060 \u2060Eplerenone: 25 \u2192 50 mg daily.
\n\u2022\u2060 \u2060Frail or elderly patients may start at 12.5 mg daily.
\n\u2022\u2060 \u2060Increase after 4\u20138 weeks; monitor potassium and renal function.
\n\u2022\u2060 \u2060Avoid initiation if eGFR <30 mL\/min\/1.73 m\u00b2 or K\u207a >5.0 mmol\/L.<\/p>\n
4.\u2060 \u2060SGLT2 Inhibitors<\/p>\n
\u2022\u2060 \u2060Dapagliflozin: 10 mg daily.
\n\u2022\u2060 \u2060Empagliflozin: 10 mg daily.
\n\u2022\u2060 \u2060Starting dose = target dose; no titration required.
\n\u2022\u2060 \u2060Avoid use in eGFR <20 mL\/min\/1.73 m\u00b2, SBP <95 mmHg, pregnancy, or type 1 diabetes.<\/p>\n
Key Message<\/p>\n
\u2022\u2060 \u2060Start all four pillars early and uptitrate together, rather than maximizing one drug before introducing the others, while closely monitoring blood pressure, heart rate, renal function, and serum potassium.<\/p>\n