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Cardiovascular

Heart failure - pharmacological management

Quadruple therapy is now the international standard for HFrEF. The NZ story is about which of the four agents are funded, when, and whether primary care can initiate them.

Reviewed May 2026 Cardiac Society NZ / BPAC 2023 NHF Australia 2018 (updated) ESC 2021

Scope: Pharmacological management of heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%) and mildly reduced/preserved ejection fraction (HFmrEF/HFpEF) in adults. Does not cover acute decompensated heart failure or device therapy.

Where they agree

  • All guidelines recommend echocardiography to confirm diagnosis and classify HF by LVEF
  • Diuretics (furosemide) for symptom relief of congestion - not disease-modifying but essential for QoL
  • All four quadruple therapy pillars are recommended for HFrEF: (1) ACEi or ARNi (sacubitril-valsartan), (2) evidence-based beta-blocker (bisoprolol, carvedilol, or metoprolol succinate), (3) mineralocorticoid receptor antagonist (MRA: spironolactone or eplerenone), (4) SGLT2 inhibitor (dapagliflozin or empagliflozin)
  • These four drug classes reduce mortality and hospitalisation independently; the combination is additive
  • Target-dose titration is important - under-dosing is common and suboptimal
  • Cardiac rehabilitation improves outcomes and QoL for stable HF patients

Where they diverge

  • Sacubitril-valsartan (Entresto): ESC 2021 recommends replacing ACEi with sacubitril-valsartan in symptomatic HFrEF on optimised background therapy. PHARMAC funds with Special Authority but criteria are restrictive
  • SGLT2 inhibitors: PHARMAC funding expanded in 2023-2024 to cover HFrEF, HFmrEF, and HFpEF - check current SA criteria
  • HFpEF management: limited disease-modifying pharmacotherapy beyond SGLT2i and diuretics; major unmet need
  • Ivabradine: ESC recommends for HFrEF with HR ≥70 bpm on maximum beta-blocker. PHARMAC funding: check current status
  • Vericiguat: ESC 2021 gives Class IIb. Not funded in NZ

Comparison

Domain NZ - BPAC / Cardiac Society 2023 AU - NHF 2018 (updated) International - ESC 2021
Diagnosis and classification Echocardiography required to confirm and classify. HFrEF: LVEF ≤40%. HFmrEF: LVEF 41-49%. HFpEF: LVEF ≥50% with evidence of structural/functional abnormality and elevated BNP.

BNP or NT-proBNP: useful for diagnosis in uncertain cases and for monitoring. BNP <35 pg/mL or NT-proBNP <125 pg/mL makes HF unlikely in non-acute setting.PHARMAC funds

Refer for echocardiography - available via cardiology or community echocardiography services. 		Consistent. NHF Australia recommends echocardiography for all patients with suspected HF. BNP/NT-proBNP as a gatekeeper before echo in uncertain cases. Consistent. ESC 2021 updated HFmrEF as a distinct category (LVEF 41-49%); previously called HFmEF. Elevated natriuretic peptides (BNP >35 or NT-proBNP >125) required for HFpEF diagnosis in non-acute setting.
ACEi/ARNi - first pillar ACEi (ramipril, lisinopril - PHARMAC-funded) as initial therapy in all HFrEF. Target maximum tolerated dose (ramipril up to 10 mg daily; lisinopril up to 35 mg daily).Funded

Sacubitril-valsartan (Entresto): funded with Special Authority - broadly: LVEF ≤40%, NYHA Class II-IV, already on optimised ACEi/ARB + beta-blocker + MRA, with specific eGFR and potassium criteria.SA required Confirm current PHARMAC SA criteria before prescribing. Transition from ACEi to sacubitril-valsartan requires 36-hour washout to avoid angioedema. Do not use ACEi + sacubitril-valsartan simultaneously. 		ACEi first-line; sacubitril-valsartan PBS-listed for HFrEF with similar background therapy requirement. Transition protocol same as international.PBS ACEi for all HFrEF patients (Class IA). Replace with sacubitril-valsartan in patients who remain symptomatic on optimised ACEi + beta-blocker + MRA (Class IB). The PARADIGM-HF trial showed sacubitril-valsartan reduced CV death and HF hospitalisation by 20% vs enalapril. Some guidelines now advocate initiating sacubitril-valsartan as first-line (bypassing ACEi) - not yet standard NZ/AU practice.
Beta-blocker - second pillar Three evidence-based beta-blockers: bisoprolol (1.25 mg → 10 mg daily), carvedilol (3.125 mg BD → 25 mg BD), metoprolol succinate (12.5-25 mg → 200 mg daily). PHARMAC funds all three.Funded

Start LOW dose and titrate slowly (increase every 2 weeks if tolerated). Initiate only when patient is clinically stable and euvolaemic - do not start during acute decompensation. Common mistake: stopping beta-blocker during decompensation - continue unless haemodynamically compromised (significant bradycardia, severe hypotension, or cardiogenic shock). 		Consistent agent selection. Same titration principles.PBS Class IA for all HFrEF. Same three agents. Target doses matter: mortality benefit is dose-dependent. Do not stop beta-blocker during mild-moderate decompensation.
MRA - third pillar Spironolactone 25-50 mg daily (PHARMAC-funded). Eplerenone (PHARMAC-funded with SA for post-MI HF): higher cost, less gynaecomastia.Funded

Monitor potassium and renal function closely - hyperkalaemia is the key risk (check at 1 week, 1 month, then 3-6 monthly). Avoid if eGFR <30 or K+ ≥5.0 mmol/L. The RALES trial (spironolactone) and EMPHASIS-HF (eplerenone) established mortality benefit. 		Consistent. Spironolactone preferred for most; eplerenone for those with gynaecomastia or post-MI HF.PBS MRA recommended for all HFrEF patients tolerating ACEi/ARB and beta-blocker (Class IA). K+ and creatinine monitoring mandatory. Finerenone (non-steroidal MRA) has emerging data in HF but is currently primarily used in T2D + CKD; not currently in mainstream HF guidelines.
SGLT2 inhibitor - fourth pillar Dapagliflozin is PHARMAC-funded for HF - confirm current Special Authority criteria. As of 2023-2024, SA has been broadened beyond HFrEF to include HFmrEF and HFpEF based on DELIVER trial evidence.SA required

Empagliflozin has evidence for HFrEF (EMPEROR-Reduced) and HFpEF (EMPEROR-Preserved) - confirm PHARMAC funding status for HF indication separately from the T2D indication. SGLT2i benefit in HF is independent of diabetes status - these drugs reduce HF hospitalisation and CV death in patients without diabetes. 		Both dapagliflozin and empagliflozin PBS-listed for HF indications (HFrEF and expanded to HFpEF based on DELIVER/EMPEROR-Preserved). No diabetes diagnosis required for HF indication.PBS Dapagliflozin and empagliflozin recommended for HFrEF (Class IA) based on DAPA-HF and EMPEROR-Reduced. Subsequent HFpEF trials (DELIVER, EMPEROR-Preserved) led to Class IIa recommendation for SGLT2i in HFpEF/HFmrEF in focused 2023 update. The mechanism in HF appears independent of glycaemic effect - haemodynamic and direct myocardial effects.
HFpEF management Diuretics for congestion. Treat underlying conditions (hypertension, AF, diabetes, obesity, sleep apnoea) aggressively - these drive HFpEF.

SGLT2i (dapagliflozin): check current SA criteria.Check SA criteria

No disease-modifying pharmacotherapy with unequivocal Class I evidence beyond SGLT2i. Spironolactone has modest evidence (TOPCAT trial was positive in Americas subgroup but overall mixed). Avoid ACEi/ARB as disease-modifying therapy in isolated HFpEF (no mortality benefit). 		Consistent. SGLT2i for HFpEF is the major new addition. Spironolactone considered in selected cases. SGLT2i receive a IIa recommendation for HFpEF (updated from ESC 2021 where no therapy had a Class I indication for HFpEF). This is the most significant recent change in HFpEF management. Treat underlying conditions aggressively.
Initiation in primary care vs secondary care Most HF patients in NZ are diagnosed in hospital or cardiology outpatient setting. Primary care role: titration of therapy, monitoring (U&E, eGFR, BP), managing decompensations, coordinating specialist review, and cardiac rehabilitation referral.

BPAC 2023 guidance supports GP initiation of SGLT2i and sacubitril-valsartan if SA criteria are met and cardiologist has confirmed diagnosis and initiated the drug class. Annual or 6-monthly review for stable HF is appropriate in primary care. 		Similar shared-care model. GPs often manage stable, optimised HF patients; specialist review for new diagnosis and drug initiation. No specific primary/secondary care allocation - titration and monitoring often occur in specialist HF clinics.

NZ clinical context

Quadruple therapy in NZ: what's funded, when to initiate, and what to check

The practical NZ quadruple therapy sequence

NZ's HF pharmacotherapy landscape has been substantially updated in recent years. The four pillars of HFrEF management are now all accessible - but three of them require Special Authority or at least SA verification.

Monitoring at each visit

BP, HR, weight (fluid status), eGFR, K+, Na+. The most common adverse effects requiring dose adjustment: hypotension (ACEi/ARNi, beta-blocker), hyperkalaemia (MRA, ACEi), bradycardia (beta-blocker), volume depletion (SGLT2i in hot weather or illness).

When to refer acutely

Features of decompensation - increasing dyspnoea, orthopnoea, weight gain >2 kg in 2 days, new S3, worsening peripheral oedema. Most decompensations can be managed with furosemide dose increase and close telephone follow-up, but severe decompensation requires hospital.

Sick day rules

Advise patients to hold ACEi/ARB, MRA, and SGLT2i (but NOT beta-blocker) if severely dehydrated, vomiting, or with acute kidney injury - the "sick day" rule. This is especially important with SGLT2i (euglycaemic DKA risk; Fournier's gangrene risk though rare).

Sacubitril-valsartan initiation in primary care

If SA criteria are met and the cardiologist has confirmed the diagnosis, GPs can transition patients from ACEi to sacubitril-valsartan. The key is: stop ACEi, wait 36 hours to prevent angioedema, then start sacubitril-valsartan 24/26 mg BD. Do not overlap ACEi and sacubitril-valsartan. Titrate up by doubling the dose every 2-4 weeks to target 97/103 mg BD.

SGLT2 inhibitor benefit is independent of diabetes

Dapagliflozin and empagliflozin reduce hospitalisation and CV mortality in HF patients without diabetes. Do not limit SGLT2i consideration to patients with concurrent diabetes. The HF benefit is a distinct indication from the diabetes indication.

Bottom line for NZ practice

What this means in the consulting room

  1. All four quadruple therapy pillars are now funded or accessible in NZ for HFrEF - ACEi/ramipril (funded), bisoprolol (funded), spironolactone (funded), dapagliflozin (funded with SA). Check PHARMAC SA for dapagliflozin HF indication at every HF review.
  2. Start ACEi and beta-blocker early and together (or in close sequence) rather than waiting to reach maximum dose of one before starting the other - trial data supports this approach.
  3. For patients on ACEi + beta-blocker + MRA who remain symptomatic, check sacubitril-valsartan SA criteria. If met, the transition from ACEi to sacubitril-valsartan reduces CV death and hospitalisation by ~20%.
  4. SGLT2i benefit in HF is independent of diabetes - do not exclude patients without T2D from dapagliflozin consideration. This is a distinct HF indication.
  5. For HFpEF: treat underlying drivers aggressively (hypertension, AF, obesity, sleep apnoea), check current SA criteria for dapagliflozin (HFpEF indication), and diurese for symptoms. This is the area with the fewest treatment options and the most need.

Sources

  1. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726.
  2. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF). N Engl J Med. 2019;381(21):1995-2008.
  3. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure (EMPEROR-Reduced). N Engl J Med. 2020;383(15):1413-1424.
  4. Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction (DELIVER). N Engl J Med. 2022;387(12):1089-1098.
  5. McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure (PARADIGM-HF). N Engl J Med. 2014;371(11):993-1004.
  6. Zannad F, McMurray JJV, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms (EMPHASIS-HF). N Engl J Med. 2011;364(1):11-21.
  7. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure (RALES). N Engl J Med. 1999;341(10):709-717.