Definition differs by source. Thai HFCT 2019 & ESC 2021/2023: HFrEF = LVEF ≤40% (Thai text: <40% / ≤35% for some add-ons). ESC 2026 merges old HFmrEF into HFrEF (LVEF <50%) and retires the term GDMT (FMT / AMT / GDIT).
4 classesBB · RAASi (ARNI/ACEi/ARB) · MRA · SGLT2i
Start togetherall four early; do not wait months between drugs
2–4 wkup-titration interval to target / max tolerated
≥3 moon optimal therapy before ICD/CRT decision
Stepwise approach
- Confirm HFrEFNT-proBNP/BNP + ECG, then echo for LVEF. Look for cause (ischaemia, valve, hypertension, tachy-arrhythmia, toxins).
- DecongestLoop diuretic for congestion only; it relieves symptoms but does not replace the 4 drugs.
- Start the 4 classes in low doseBeta-blocker once euvolaemic; RAASi, MRA and SGLT2i can start together (check K⁺, creatinine, SBP first).
- Up-titrate every 2–4 weeksAim for target dose or maximum tolerated; check K⁺/creatinine/BP at each step.
- Reassess at ≥3 monthsRepeat echo. LVEF ≤35% + NYHA II–III on optimal therapy → ICD / CRT assessment. Persistent symptoms → add-on therapy.
Which RAAS agent?
HFrEF, no contraindication to RAASi
↓
ESC 2021/2023ARNI (Entresto) recommended to replace ACEi (I-B); ACEi still an accepted start (I-A).
Thai HFCT 2019ACEi/ARB first + BB + MRA. ARNI instead of ACEi/ARB if still symptomatic (I-B). De novo ARNI only IIb-C (SBP >100, age <75).
Cannot take ARNI / ACEiARB (valsartan, candesartan). ACEi cough → ARB. ARNI angioedema → no ACEi, no ARNI.
Thai practice: follow the Thai column unless local protocol (or ARNI access) says otherwise; where the sources conflict this page flags it.
1 Beta-blocker
| Drug | Start | Target | Notes |
|---|---|---|---|
| BisoprololConcor | 1.25 mg OD | 10 mg OD | CIBIS-II. Once-daily; good for adherence. |
| CarvedilolDilatrend | 3.125 mg BID | 25 mg BID | 50 mg BID if >85 kg (ESC). COPERNICUS. Alpha-blockade: watch BP; useful if hypertensive. |
| Metoprolol succinate ERBetaloc ZOK | 12.5–25 mg OD | 200 mg OD | MERIT-HF. Succinate ER only — not tartrate. |
Start when euvolaemic, not in shock. Double dose every 2–4 wk. Do not stop abruptly. Continue in decompensation unless cardiogenic shock / severe bradycardia.
2 RAAS inhibitor
| Drug | Start | Target | Notes |
|---|---|---|---|
| Sacubitril/valsartanEntresto | 24/26 or 49/51 mg BID | 97/103 mg BID | PARADIGM-HF. 24/26 if RAASi-naïve/low dose; 49/51 if on ≥ enalapril 10 mg/d or valsartan 160 mg/d. 36 h ACEi washout. Thai: titrate over 3–4 wk (49/51 start) or 6 wk (24/26 start). |
| EnalaprilRenitec | 2.5 mg BID | 10–20 mg BID | SOLVD / CONSENSUS. |
| RamiprilTritace | 1.25–2.5 mg OD | 10 mg OD | Or 5 mg BID. |
| LisinoprilZestril | 2.5–5 mg OD | 20–35 mg OD | Thai table: target 20–40 mg OD. |
| CaptoprilCapoten | 6.25 mg TID | 50 mg TID | Short half-life; high pill burden. |
| Valsartan (ARB)Diovan | 40 mg BID | 160 mg BID | Val-HeFT. If ACEi-intolerant. |
| Candesartan (ARB)Atacand / Blopress | 4 mg OD | 32 mg OD | CHARM-Alternative. |
| Losartan (ARB)Cozaar | 25–50 mg OD | 150 mg OD | Thai table: 50–150 mg OD. Weaker HFrEF outcome data. |
ARNI contraindications (Thai 2019): SBP <90 · eGFR <30 · K⁺ >5.2 · prior angioedema · pregnancy. Never with an ACEi.
3 MRA
| Drug | Start | Target | Notes |
|---|---|---|---|
| SpironolactoneAldactone | 12.5–25 mg OD | 25 mg OD* | RALES. *ESC target 50 mg. Thai: avoid ≥50 mg/day. Gynaecomastia ~10%. |
| EplerenoneInspra | 25 mg OD | 50 mg OD | EMPHASIS-HF. No anti-androgen effect; use if spironolactone not tolerated. |
Source conflict: ESC target spironolactone 50 mg OD vs Thai HFCT 2019 “avoid ≥50 mg/day”. This page follows Thai (target ≈25 mg OD).
4 SGLT2 inhibitor
| Drug | Start | Target | Notes |
|---|---|---|---|
| DapagliflozinForxiga | 10 mg OD | 10 mg OD | DAPA-HF (eGFR ≥30 enrolled). No titration. With or without diabetes. |
| EmpagliflozinJardiance | 10 mg OD | 10 mg OD | EMPEROR-Reduced (eGFR ≥20 enrolled). No titration. |
Thai CPG gap: HFCT 2019 predates DAPA-HF/EMPEROR-Reduced and has no SGLT2i recommendation for HFrEF. Class I comes from ESC 2021/2023 (and ESC 2026 FMT).
Before starting
| Drug | Do not start / hold if | Recheck |
|---|---|---|
| ARNI / ACEi / ARB | SBP <90 · K⁺ >5.2 (ARNI) · eGFR <30 (ARNI) · angioedema · pregnancy · bilateral RAS | K⁺ & creatinine 1–2 wk after each dose step |
| Beta-blocker | Decompensated/wet, shock, HR <50, 2°/3° AV block, severe asthma | HR, BP, weight at each step |
| MRA | K⁺ >5.0 · Cr >2.5 (M) / >2.0 (F) · eGFR <30 · with ACEi + ARB together | K⁺ within 7 d of any dose increase; then ≥ every 3 mo |
| SGLT2i | Type 1 DM / DKA risk · recurrent genital infection · volume depleted (eGFR below trial limits) | Volume status; expect small early eGFR dip |
Switching to ARNI (Thai 2019 Table 16)
| Current RAASi | ARNI start | Titrate to 97/103 BID |
|---|---|---|
| ≥ enalapril 10 mg/d, lisinopril 10, perindopril 4, ramipril 5, losartan 50, valsartan 160, candesartan 16, irbesartan 150, olmesartan 10, telmisartan 40 mg/d | 49/51 mg BID | over 3–4 weeks |
| Lower doses than above · RAASi-naïve · hypotension risk | 24/26 mg BID | over ~6 weeks |
ACEi → ARNI: stop ACEi ≥36 h first (angioedema). ARB → ARNI: switch directly, no washout.
Practical rules
- Accept small rises: creatinine up to ~30% and K⁺ ≤5.5 are tolerated; larger → review dose, volume, NSAIDs, K⁺ supplements.
- Avoid NSAIDs, K⁺ supplements and non-DHP CCB (diltiazem/verapamil) in HFrEF.
- Low BP alone is not a reason to drop a class: reduce diuretic first if not congested, then stagger the doses.
- Do not combine MRA + ACEi + ARB (Thai 2019).
Persistent symptoms on the 4 classes
| Option | Dose | Use when | Source / strength |
|---|---|---|---|
| IvabradineProcoralan | 5 mg BID → 7.5 mg BID | Sinus rhythm, HR >70 despite max-tolerated BB, LVEF ≤35% | Thai 2019 IIa; SHIFT |
| Hydralazine + ISDNApresoline + Isordil | 25–75 mg + 20–40 mg TID | Cannot use ACEi/ARB/ARNI (intolerance, renal) | Thai 2019 IIb |
| DigoxinLanoxin | 0.125 mg OD | Sinus rhythm, still symptomatic on optimal therapy; AF rate control | Thai 2019 IIb; keep level <1.0 ng/mL |
| IV ferric carboxymaltoseFerinject | per weight/Hb table | Symptomatic HFrEF with iron deficiency (ferritin <100, or 100–299 with TSAT <20%) | ESC 2023 FU: I-A symptoms/QoL, IIa-A fewer HF admissions |
| VericiguatVerquvo | 2.5 → 10 mg OD | Worsening HF event despite therapy (VICTORIA) | ESC 2021 IIb. Not in Thai CPG; availability limited |
Devices (after ≥3 months optimal therapy)
- ICD: LVEF ≤35%, NYHA II–III, expected survival >1 y (ESC 2021). Ischaemic and non-ischaemic criteria differ.
- CRT: LVEF ≤35% with LBBB and wide QRS (ESC 2021: ≥150 ms I-A; 130–149 ms IIa-B).
Refer to cardiology/EP; Thai 2019 has its own device section — verify locally before listing.
Avoid / harmful in HFrEF: NSAIDs, thiazolidinediones, non-DHP CCB, class I antiarrhythmics, dronedarone, and ARNI + ACEi together.
What changed vs the old page
| Item | Thai HFCT 2019 | ESC 2023 FU | ESC 2026 |
|---|---|---|---|
| HFrEF LVEF | <40% | ≤40% | <50% (HFmrEF merged) |
| Core therapy | ACEi/ARB, BB, MRA (I-A). ARNI next step. | ARNI/ACEi + BB + MRA + SGLT2i (4 pillars) | “FMT” — one drug per class, together |
| ARNI | Replace ACEi/ARB if symptomatic (I-B); de novo IIb-C | Replace ACEi (I-B) | FMT RAASi option |
| SGLT2i | Not addressed | I-A (dapagliflozin / empagliflozin) | FMT |
| MRA dose | Low dose; avoid ≥50 mg spironolactone | Spironolactone target 50 mg | FMT (see full text) |
| Terminology | GDMT | GDMT | FMT / AMT / GDIT |
Thai CPG gap: a post-2019 Thai HF update was not found. SGLT2i-in-HFrEF, ARNI first-line and the 4-pillar simultaneous start come from ESC, not the Thai CPG.
ESC 2026 caveat: the ESC 2026 items here come from the linked HF ESC 2026 reference, built from secondary coverage — verify against the full text (Eur Heart J 2026) before changing practice.