A 65-year-old woman with NYHA Class II heart failure (EF 35%) is on ramipril 5 mg daily, bisoprolol 2.5 mg daily, and spironolactone 25 mg daily. She reports persistent dyspnoea on exertion and ankle oedema. Her BP is 105/68 mmHg, HR 72/min, K^+^ 4.2 mEq/L, and eGFR 52 mL/min/1.73m². What is the most appropriate next step in management?

Explanation

## Clinical Context This patient has symptomatic systolic HF (EF 35%, NYHA II) on triple therapy (ACE-I, beta-blocker, aldosterone antagonist) at modest doses. She remains dyspnoeic despite guideline-directed medical therapy, indicating inadequate neurohormonal blockade. ## Why ARNI Is the Next Step **Key Point:** The fourth pillar of GDMT for systolic HF is replacement of ACE-I/ARB with an ARNI (sacubitril/valsartan). ARNIs provide dual benefit: ARB effect (valsartan) + neprilysin inhibition (sacubitril), reducing natriuretic peptide degradation and enhancing vasodilation and natriuresis. **High-Yield:** PARADIGM-HF trial demonstrated that sacubitril/valsartan reduces mortality and HF hospitalisation by ~20% compared to enalapril in systolic HF. This is now Class I recommendation for EF ≤40% [cite:Harrison 21e Ch 297]. **Clinical Pearl:** ARNI transition protocol: 1. Discontinue ACE-I/ARB for 24–48 hours (washout period) 2. Start sacubitril/valsartan 24/26 mg twice daily 3. Titrate to target: 97/103 mg twice daily over 2–4 weeks 4. Monitor BP, K^+^, and Cr at 1–2 weeks and then regularly **Mnemonic:** ARNI = **A**ngiotensin **R**eceptor **N**eprilysin **I**nhibitor — blocks two pathways simultaneously. ## Why ARNI Over ACE-I Escalation This patient is on ramipril 5 mg (below target of 10 mg), but the evidence-based approach is not to escalate the ACE-I further. Instead, replacing it with an ARNI provides superior mortality reduction and is the next step in the algorithm. The GDMT sequence is: 1. ACE-I/ARB + beta-blocker 2. Add aldosterone antagonist 3. **Replace ACE-I/ARB with ARNI** ← Current step 4. Add SGLT2 inhibitor or ivabradine if HR >70 or EF <27% ## Dosing and Monitoring | Parameter | Baseline | At 1–2 weeks | At 4 weeks | Target | | --- | --- | --- | --- | --- | | Sacubitril/valsartan | 24/26 mg BD | Check BP, K^+^, Cr | Titrate if tolerated | 97/103 mg BD | | Systolic BP | 105 | Monitor; avoid <90 | Maintain >90 | 90–110 | | K^+^ | 4.2 | <5.5 acceptable | <5.5 acceptable | <5.5 | | eGFR | 52 | Monitor decline | Acceptable if stable | >30 | **Tip:** Sacubitril/valsartan is contraindicated in pregnancy (teratogenic) and angioedema history with ACE-I. This patient has neither. ## Why Other Options Are Suboptimal **Increase bisoprolol:** Beta-blocker is already at 2.5 mg daily (low-moderate dose). While titration is part of GDMT, the priority in a symptomatic patient on triple therapy is to add the fourth pillar (ARNI), not escalate an existing agent without evidence of underdosing (e.g., HR >70 or recent decompensation). **Add furosemide:** Diuretics are for symptomatic relief of congestion (pulmonary oedema, peripheral oedema) but do NOT reduce mortality. This patient has ankle oedema (mild congestion), but the primary step is to optimise GDMT. Diuretics may be added if congestion worsens, but they are not the next step in the algorithm. **Initiate ivabradine:** Ivabradine (selective I~f~ inhibitor) is indicated in systolic HF with EF ≤35% and resting HR ≥70 bpm despite beta-blocker. This patient's HR is 72 (borderline), but ivabradine is a fifth-line agent, reserved after ARNI and SGLT2i are optimised. It is not the next step here.