Asian Pacific Society of Cardiology Consensus Statements on the Management of Worsening Heart Failure

In 2023, the Asian Pacific Society of Cardiology (APSC) issued consensus statements on the management of chronic heart failure (CHF) to improve the quality of care given to patients with CHF in the region.¹ However, heart failure (HF) patients in the Asia-Pacific region face multiple challenges with disease management, which may lead to worsening HF. One of these challenges is the suboptimal use of optimised medical therapy (OMT) immediately after discharge and during the maintenance phase of treatment. Because recent evidence from the STRONG-HF trial underscores the profound benefit of rapid uptitration of OMT in patients discharged from hospital for worsening HF, there is a need to improve both the level and quality of care provided to HF patients in the region.²

Hence, the APSC developed these consensus recommendations, with general cardiologists and internal medicine specialists practising cardiology as the intended readers, to guide them in the appropriate evaluation and management of worsening HF. In addition, these statements also aim to update the recommended medical therapy for patients with worsening HF upon discharge, based on the latest data.

Methods

The APSC convened an expert consensus panel to review the literature on the assessment and management of worsening HF, discuss gaps in current management, determine areas where further guidance is needed and develop consensus recommendations. The 19 experts on the panel are either members of the APSC who were nominated by national societies and endorsed by the APSC consensus board or invited international experts. The consensus panel defined worsening HF as the escalation of HF signs and symptoms on a background of chronic HF in an inpatient or outpatient setting, despite previously stable therapy, or a patient who requires urgent escalation of therapy, usually centred on the administration of diuretics.

After a comprehensive literature search, selected applicable articles were reviewed and appraised using the Grading of Recommendations Assessment, Development, and Evaluation system.³ Based on this system, the levels of evidence were designated as:

1. High (authors have high confidence that the true effect is similar to the estimated effect).
2. Moderate (authors believe that the true effect is probably close to the estimated effect).
3. Low (true effect might be markedly different from the estimated effect).
4. Very low (true effect is probably markedly different from the estimated effect).

As indicated by these levels, the authors adjusted the level of evidence if the estimated effect, when applied in the Asia-Pacific region, could differ from the published evidence because of various factors such as ethnicity, cultural differences and/or healthcare systems and resources.

The available evidence was then discussed and consensus recommendations were developed during two virtual consensus meetings (December 2024 and February 2025). The final consensus statements were then put to an online vote, with each recommendation being voted on by each panel member using a three-point scale (i.e. agree, neutral or disagree). Consensus was defined as 80% or more of votes being ‘agree’ or ‘neutral’ for a given recommendation. In the case of non-consensus, the recommendations were further discussed using email communication and then revised accordingly until the criteria for consensus were fulfilled.

The authors acknowledge that patients with worsening HF may present with acute coronary syndrome and/or cardiogenic shock. However, the management of these two conditions is beyond the scope of these statements. Furthermore, the APSC has previously published consensus statements on the management of cardiogenic shock.⁴

Recommendations

Use of N-terminal Pro B-type Natriuretic Peptide in the Acute and Post-acute Setting

In a previous consensus statement, the APSC recommended the measurement of N-terminal pro-B-natriuretic peptide (NT-proBNP) in patients suspected of CHF on top of clinical examinations and imaging studies.¹ More recently, there is growing evidence supporting the role of NT-proBNP measurement in the management of worsening HF, wherein NT-proBNP may be used to both diagnose worsening clinical status and for prognostication. Most published studies use a threshold of at least a 30% increase in NT-proBNP levels to indicate worsening HF.⁵ However, a few expert panellists note that a fixed cut-off is not necessary for many patients and that the trend is more clinically informative, even if the change is less than 30%.

The role of NT-proBNP measurement was further supported by the STRONG-HF trial.² This was a multinational open-label randomised parallel-group trial that included haemodynamically stable adult patients with acute HF who were not treated with full doses of guideline-directed medical therapy. The STRONG-HF trial aimed to compare a high-intensity intervention involving rapid uptitration of HF treatments versus usual care. In that trial, enrolment was guided by NT-proBNP measurement, wherein patients had to have an initial BNP measurement of >2,500 pg/ml, followed by a greater than 10% decrease between screening and before randomisation (but still greater than 1,500 pg/ml). This strategy aimed to identify patients who were still at risk but were showing improvement during hospitalisation, providing information on a patient’s clinical status upon discharge. STRONG-HF also used regular NT-proBNP measurement to closely monitor the clinical status of enrolled patients over 2 months, including the 2-week uptitration phase.

The authors acknowledge that rapid NT-proBNP measurement helped identify candidates for treatment, in prognostication and in monitoring the safety and efficacy of the intervention. However, they also note that measurement of NT-proBNP is not readily accessible in many countries in the Asia-Pacific region. Furthermore, the cost of this test is not negligible, which may hinder its repeated use. Nonetheless, this test may be considered before discharge and/or during the first follow-up visit to inform clinicians on a patient’s present clinical status, including congestion, clinical course, prognosis and eligibility for and safety of rapid uptitration.

Decongestion is Key in the Acute Setting

Loop diuretics are recommended as first-line agents to induce euvolaemia in patients with congestion (Figure 1) by increasing the renal excretion of salt and water.^1,6 In worsening HF, loop diuretics are preferred due to their rapid onset of action, diuretic efficacy without marked alterations in electrolyte levels and wide therapeutic window. The choice of loop diuretic, especially in the Asian-Pacific region, is usually driven by drug availability. The lowest effective dose is recommended to minimise adverse effects; however, the dose may be increased in patients with a poor initial response.

On top of increasing the dose of loop diuretic, the addition of a second diuretic, such as thiazide diuretics or IV acetazolamide, is a reasonable option. The ADVOR study, a multicentre randomised parallel-group double-blind placebo-controlled trial, showed that in patients with worsening HF and an NT-proBNP level >1,000 pg/ml or a B-type natriuretic peptide level >250 pg/ml, IV acetazolamide was superior to placebo in reducing rehospitalisation for HF or all-cause death.⁷ Conversely, the CLOROTIC trial found that hydrochlorothiazide was more effective than placebo in rapidly reducing body weight in the acute setting, but was similar to placebo in terms of patient-reported dyspnoea and HF rehospitalisation or all-cause death.⁸ Patients on hydrochlorothiazide also had a higher risk of increases in serum creatinine, underscoring the importance of monitoring in patients on combination therapy.⁸

Patients who have been stabilised may be switched to oral diuretic therapy, such as oral furosemide.⁶ However, if the response is inadequate, oral bumetanide or torsemide may be considered.^9,10 Bumetanide has more predictable absorption and greater bioavailability, and is readily available in many countries in the Asia-Pacific region.⁹ Similarly, torsemide has high oral bioavailability, and its efficacy over oral furosemide is supported by small randomised controlled trials.¹⁰

Tolvaptan may also be used as an adjunct in decongesting patients with worsening HF. The TACTICS-HF study, a randomised double-blind placebo-controlled trial, found that tolvaptan, in addition to a fixed-dose furosemide regimen as background therapy, was superior to placebo in improving fluid loss, especially in those who showed some response to diuretics.¹¹ However, the addition of tolvaptan did not improve the response rate to decongestion. Patients with hyponatraemia may also benefit from tolvaptan therapy because its aquaretic action tends to increase serum sodium.

The routine use of inotropes is not recommended for decongestion. The use of inotropes should be reserved for patients with symptomatic hypotension and evidence of hypoperfusion.⁶ Similarly, the use of nitrates may be considered to reduce preload in patients with worsening HF and persistent pulmonary congestion despite systemic decongestion, especially among patients with hypertension.¹²

Oral Pharmacological Therapy in Worsening Heart Failure with Reduced Ejection Fraction (Ejection Fraction ≤40%)

The foundational oral pharmacological therapy for HF with reduced ejection fraction (HFrEF) is well established and includes a renin–angiotensin system inhibitor, such as the preferred angiotensin receptor–neprilysin inhibitor (ARNI) or an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), a β-blocker, a mineralocorticoid receptor antagonist (MRA) and a sodium–glucose cotransporter 2 inhibitor (SGLT2i).¹ Combining these four agents addresses multiple pathophysiological mechanisms of HFrEF and provides prolonged survival, reduced hospitalisation and improved patient-reported outcomes.¹

In patients with worsening HF, this foundational quadruple therapy should be initiated in a timely manner, as demonstrated by the STRONG-HF study. As previously mentioned, STRONG-HF compared high-intensity intervention involving rapid uptitration of HF treatments versus usual care.² Rapid uptitration was defined as achieving 100% of recommended doses within 2 weeks of discharge and included four scheduled outpatient visits over the 2 months after discharge, with close monitoring of clinical status and laboratory parameters including NT-proBNP. STRONG-HF found that the high-intensity care group had a lower risk of all-cause death or HF readmission by day 180 compared with the usual care group (15.2% versus 23.3%, respectively; p=0.0021).²

Based on that study, the authors recommend a similar rapid uptitration for patients with worsening HF. This is facilitated by the initiation of all four drug classes before hospital discharge, as shown in Figure 2. The sequence of initiation should be guided by the principles presented in Table 1 to ensure patient safety during rapid uptitration. Finally, the authors recommend the achievement of the target or maximally tolerated doses within 3 months (ideally within 6 weeks) after discharge, noting that the 2-week target of STRONG-HF is challenging in real-world practice, especially in many countries in the Asia-Pacific region, where there are healthcare resource and real-world logistical issues.

In HFrEF patients (ejection fraction [EF] ≤35%) in sinus rhythm and a resting heart rate ≥70 BPM who remain symptomatic despite OMT (including maximally tolerated β-blocker), or in those who cannot tolerate β-blockers, ivabradine should be considered. The role of ivabradine in chronic HF has been previously described by the APSC.¹ The rate-lowering action of ivabradine is associated with a reduction in cardiovascular (CV) mortality and HF hospitalisation in patients already on an ACEI/ARB, a β-blocker and an MRA, or in those who cannot tolerate β-blocker therapy.^13,14

Based on the AFFIRM-HF study, in 2023 the APSC recommended the use of intravenous ferric carboxymaltose in patients with symptomatic HFrEF and iron deficiency (serum ferritin <100 ng/ml or serum ferritin 100–299 ng/ml with transferrin saturation <20%).^1,15 More recently, the IRONMAN study found that ferric derisomaltose may also improve outcomes, although only 15% of the patients in that study were hospitalised and the study narrowly missed statistical significance.¹⁶

The current consensus also reiterates the conditional use of other adjunctive pharmacotherapy previously recommended by the APSC for chronic HFrEF.¹ This includes vericiguat and digoxin in HFrEF patients who have worsening HF despite OMT, and the combination of a nitrate plus hydralazine for HFrEF patients who cannot tolerate ACEI, ARB or ARNI.^17–19

Oral Pharmacological Therapy in Worsening Heart Failure with Mildly Reduced Ejection Fraction (Ejection Fraction 41–49%)

Since the publication of the APSC Consensus Statements on the Management of Chronic HF in 2023, SGLT2i have become more established in the management of HF with reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF).¹ Although the two landmark studies, EMPEROR-Preserved and DELIVER, included both patients with HFmrEF and HFpEF, subgroup analyses of the two trials showed no significant interaction between their primary outcomes and EF subgroup.^20,21 This indicates that empagliflozin or dapagliflozin should be used in patients with HFmrEF, and the panel decided to increase the strength of the recommendation for this treatment.

Emerging evidence also shows a benefit with the use of an MRA in patients with HFmrEF. In the FINEARTS-HF trial, patients with HFmrEF or HFpEF were randomised to receive finerenone (at a maximum dose of 20 or 40 mg once daily) or placebo, on top of standard of care.²² The study found that finerenone reduced the risk of the primary endpoint of worsening HF events and death from CV causes by 16% (RR 0.84; 95% CI [0.74–0.95]; p=0.007).²² Subgroup analysis suggested that patients with worse EF (e.g. those with HFmrEF) tended to benefit more from treatment, although the differences between the groups were not significant.²²

Finally, no change was made in the recommendations regarding the use of an ARNI/ACEI/ARB, combined with a β-blocker, in patients with HFmrEF, based on existing evidence.^1,23–27

Pharmacological Therapy: Worsening Heart Failure With Preserved Ejection Fraction (Ejection Fraction ≥50%)

As with HFmrEF, the role of SGLT2i in the management of HFpEF has increased due to the results of the EMPEROR-Preserved and DELIVER trials.^20,21 Hence, the expert panel voted to raise the strength of recommendation for this treatment for patients with HFpEF. Similarly, the expert panel also voted to increase the strength of recommendation for MRAs, based on the compelling results of the FINEARTS-HF trial, wherein 64% of enrolled patients had HFpEF.^22,28 However, the strength of recommendation was tempered by weaker evidence from TOPCAT, which showed that spironolactone was able to reduce only the risk of HF hospitalisation and was associated with adverse effects, such as hyperkalaemia and increasing creatinine levels.²⁹

No change was made in the recommendations regarding the use of an ARNI/ACEI/ARB, combined with a β-blocker, in patients with HFpEF, based on the lack of new evidence.^1,24,30,31 The authors also recognised that the evidence for ARBs in HFpEF patients shows interstudy inconsistency.^32,33 Hence, more established treatments should be prioritised in HFpEF patients.

Finally, evidence is growing on the benefits of a glucagon-like peptide 1 receptor agonist (GLP-1RA) in patients with HFpEF. Specifically, the STEP-HFpEF and STEP-HFpEF DM studies both showed that semaglutide was superior to placebo in improving exercise capacity and quality of life in patients with HFpEF and obesity.^34,35 Similarly, the SUMMIT trial showed that tirzepatide was associated with a lower risk of CV death or worsening HF than placebo and improved health status in patients with HFpEF and obesity.³⁶

Conclusion

The 26 statements presented here aim to guide clinicians based on the most updated evidence and collective expert opinion from the Asia-Pacific region. However, given the varied clinical situations and healthcare resources present in the region, these recommendations should not replace, but rather augment, clinical judgement. The management of worsening HF should be individualised, taking into account a patient’s clinical characteristics, as well as patient and caregiver concerns and preferences. Clinicians should also be aware of the challenges that may limit the applicability of these consensus recommendations in their centre, such as access to specific interventions and technologies, the availability of resources (including the competency level of clinical staff), accepted local standards of care, cultural factors and one’s own experience and expertise. Nonetheless, these consensus statements could help create and improve protocols and pathways for the management of worsening HF in centres across the Asia-Pacific region to best benefit patients.