Speaker Series: Heart Failure Management in 2023

A RESEARCH REVIEW™

Making Education Easy

About the speaker

Associate Professor

(Hon) Gerry Devlin

Dr Gerry Devlin is an experienced general cardiologist and an Honorary Associate Professor in Medicine with the University of Auckland. Gerry has a special interest in the prevention and management of coronary artery disease, hypertension and heart failure.

Abbreviations used in this review

ACE = angiotensin converting enzyme

AF = atrial fibrillation

ARB = angiotensin receptor blocker

ARNI = angiotensin receptor neprilysin inhibitor

BMI = body mass index

BP = blood pressure

BPM = beats per minute

CR = controlled release

CV = cardiovascular

ECG = echocardiogram

EF = ejection fraction

ESC = European Society of Cardiology

ESM = early systolic murmur

GI = gastrointestinal

Hb = haemoglobin

HF = heart failure

HFmrEF = heart failure minimally reduced ejection fraction

HFpEF = heart failure preserved ejection fraction

HFrEF = heart failure reduced ejection fraction

HR = hazard ratio

JVP = jugular venous pressure

LAD = left anterior descending artery

LDLC = low-density lipoprotein cholesterol

LV = left ventricular

LVH = left ventricular hypertrophy

MI = myocardial infarction

MRA = mineralocorticoid receptor antagonist

NNT = number needed to treat

NT-pro BNP = n-terminal prohormone brain natriuretic

peptide

NYHA = New York Heart Association

NSAID = non-steroidal anti-inflammatory drugs

PCI = percutaneous coronary intervention

QoL = quality of life

SGLT2 = sodium/glucose cotransporter

T2D = type 2 diabetes

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Heart Failure Management in 2023: Challenges and Opportunities

2023

This publication summarises a presentation given by Associate Professor Gerry Devlin at the 2023 Goodfellow Symposium. With the aid of case studies, Dr Devlin discussed the evidence supporting the early and optimal use of foundational medicines in the management of heart failure with both reduced and preserved ejection fractions, providing practical recommendations for the management of heart failure in primary care. This review is sponsored by an educational grant from Boehringer Ingelheim and Eli Lilly.

Epidemiology

The burden HF places on health systems around the world is substantial. The NZ situation is similar where there were estimated to be 68,000 adults with HF in 2021/22.1 The prognosis for these patients is frequently poor with one in three who present to hospital with HFrEF dying within 3 years.2 Although the prognosis is better for patients who present with HFpEF, there is still significant morbidity and mortality in this group at 3 years. Hospitalisation with HF increases a patient’s mortality risk six-fold. The burden of HF is also higher in Māori and Pacific Island communities which is unacceptable.

Patients with HF interact with primary care on average 12 times per year, with three consultations specifically related to HF symptoms. These are opportunities for primary care to help patients and their whānau improve patient health and keep them living in the community.

CASE STUDY 1: Typically seen in primary care with class III-IV symptoms, i.e. breathless on minimum exertion and waking at night with breathlessness

Medical history Examination and investigations Medicines at discharge

• 64-year-old male

• NYHA Class III-IV symptoms

• Anterior MI 2 years prior with late presentation and did not receive reperfusion therapy

• Angiography was performed after 4 days and PCI due to total LAD occlusion

• EF was 40% at discharge

• BP 150/94 mmHg

• Tachycardiac with irregular rate of 100 bpm

• No murmurs and occasional bilateral crackles

• JVP was not elevated

• Chest X-ray revealed cardiomegaly and interstitial oedema

• ECG shows sinus tachycardia with Q-wave anterior to prior MI

• NT-pro BNP = 564 pmol/L (elevated)

• Renal function is normal

• HbA1c = 44 mmol/mol

• Aspirin 100 mg/day

• Cilazapril 1 mg/day

• Metoprolol CR 23.75 mg/day

• Atorvastatin 20 mg/day

This patient has advanced symptomatic HF. A cardiac insult has affected his LV function, resulting in HFrEF. Medication compliance has been erratic and he has not attended primary care for 18 months.

Where do we begin with this patient?

Dr Devlin emphasised that it is important to have clinical objectives with any HF patient (HFrEF or HFpEF):3,4

1. Make the patient feel better by reducing symptoms and improving QoL.

2. Improve the prognosis by reducing mortality and preventing hospitalisation via evidence-based care.

3. Prevent disease progression, where possible, through management of factors such as blood pressure and coronary artery disease.

It is not sufficient to simply up-titrate the patient’s diuretic dose and leave other treatments unchanged because intensification of diuretic therapy is associated with poor outcomes. Increasing the diuretic dose for a patient with HF may help to relieve symptoms, but in the long-term it is a poor prognostic marker that in terms of mortality is approximately equivalent to hospitalisation (Figure 1). Consideration of diuretic up-titration should therefore be a checkpoint, potentially triggering additional interventions to improve the patient’s prognosis.

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ESC 2021 guidelines

Dr Devlin highlighted, and later expanded upon, the ESC 2021 HF guidelines recommending (level 1A) four pharmaceutical interventions for patients with NYHA class II-IV with LVEF ≤40% to reduce the risk of HF hospitalisation and death:6

1. An ACE inhibitor.

2. A beta-blocker.

3. An MRA.

4. Dapagliflozin or empagliflozin.

The dosing of ACE inhibitors and beta-blockers is important. At a minimum, the aim should be to achieve at least 50% of the recommended dose. Reaching <50% of the recommended ACE inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or HF hospitalisation.5 Patients reaching 50-99% of the recommended dose had a comparable risk of death or HF hospitalisation as those achieving ≥100% (Figure 2). ARBs are being increasingly initiated in preference to ACE inhibitors for HFrEF because the subsequent transition to an ARNI may be easier. ARBs are as effective, but not superior to an ACE inhibitor for HFrEF as two studies have shown no significant difference in outcomes for patients treated with either medicine.8,9

Mineralocorticoid receptor antagonists

The recommendation for MRA treatment in the ESC 2021 HF guidelines has undergone an important change since 2016. An MRA should now be considered early for asymptomatic patients with HFrEF.6 Previously, the recommendation was for MRA initiation for patients who remained symptomatic following treatment with an ACE inhibitor and a betablocker. Combining an ACE inhibitor, a beta-blocker and an MRA can reduce mortality over 1-3 years by 50-60%.10

Dr Devlin pointed out that MRA treatment is an opportunity to improve outcomes for HF patients in New Zealand because historically this class of medicine has been viewed with caution due to the risk of hyperkalaemia and worsening renal function. Treatment with an MRA needs to be considered more often and earlier in patients with HFrEF.

Dr Devlin emphasised the importance of explaining the expected benefits of treatments to patients when medicines are initiated. In the case of spironolactone, treatment is given to improve symptoms, prevent worsening HF and to increase survival. Symptom improvement should occur within a few weeks of beginning treatment. Due to the risk of renal complications during acute illness, patients should be advised to avoid over-the-counter NSAIDs and to temporarily stop spironolactone and contact a physician if diarrhoea and/or vomiting occurs. Painful gynaecomastia is the most frequent reason for patients being unable to tolerate spironolactone.

Eplerenone is funded indefinitely under Special Authority for patients with HF and EF <40% who are either intolerant to optimal dosing of spironolactone or who experience a clinically significant adverse event while taking an optimal dose of spironolactone. This means any prescriber who is treating a patient with HF can potentially prescribe funded eplerenone. The dosing of eplerenone is the same as for spironolactone.

Dapagliflozin or empagliflozin

A meta-analysis of the EMPEROR-Reduced and DAPA-HF trials (n = 8,474) found that in patients with HFrEF, SGLT2 inhibitors were associated with significant reductions in end-points, including:11

• 13% reduction in all-cause mortality (HR 0·87, 95% CI 0·77–0·98; p=0·018)

• 14% reduction in CV mortality (HR 0·86, 0·76–0·98; p=0·027)

• 26% relative reduction in the combined risk of CV death or first HF hospitalisation (HR 0·74, 0·68–0·82; p<0·0001)

• 25% decrease in the composite of recurrent HF hospitalisations or CV death (HR 0·75, 0·68–0·84; p<0·0001)

• Reduced risk of the composite renal endpoint (HR 0·62, 0·43–0·90; p=0·013)

The benefit of SGLT2 inhibitors in patients with HFrEF occurred regardless of the presence or absence of diabetes, the age of the patient, their gender, the presence or absence of ARNI treatment or their baseline health status. Furthermore, the benefit of an ARNI appears to be augmented by SGLT2 inhibitor treatment. The reduced progression or renal dysfunction in HF patients is an important additional benefit of SGLT2 inhibitor treatment.

Sacubitril/valsartan

The ESC 2021 guidelines state as evidence level 1B that:6

• Sacubitril/valsartan is recommended as a replacement for an ACE inhibitor in patients with HFrEF to reduce the risk of HF hospitalisation and death.

Sacubitril/valsartan is associated with:

• A 20% reduction in the risk of CV mortality, compared to an ACE inhibitor.12

• A 21% reduction in the risk of HF hospitalisation, compared to an ACE inhibitor.12,13

• Improved physical and social activities and improved QoL.14

• Comparable safety and superior efficacy vs ACE inhibitors when initiated after acute HF decompensation.13,15

SGLT2 inhibitors and ARNI can be safely initiated prior to discharge

Two important changes to the ESC 2021 guidelines are:6

• Optimal evidence-based oral medical treatment should be administered before discharge.

• An early follow-up visit occurs 12 weeks after discharge to assess signs of congestion, drug intolerance and to up-titrate evidence-based therapy.

These recommendations recognise the importance of establishing HFrEF patients on optimal care, before they are discharged from hospital, and of continuing to up-titrate therapy.

Dr Devlin highlighted data from the PIONEER-HF study showing that it is safe to initiate sacubitril/ valsartan in hospital following an admission for HFrEF.15

Safety and efficacy data from the EMPULSE trial show that in patients hospitalised with acute HFrEF and HFpEF, treatment with empagliflozin resulted in significant clinical benefit within 90 days, QoL improvements, and greater reductions in NT-pro BNP, compared to placebo with no safety concerns.16

Figure 2: Adjusted mortality rates for patients receiving 0, 1-49, 50-99% or ≥100% of the recommended ACE inhibitor/ARB or beta-blocker dose. Adapted from Ouwerkerk et al (2017).7

Figure 1: All-cause mortality after first manifestation of worsening HF in enalapril treated patients in the PARADIGM-HF trial. Adapted from Okumura et al (2016).5

Heart Failure Management in 2023: Challenges and Opportunities

Combination therapy

A meta-analysis of 75 trials (>95,000 participants) demonstrated that optimised, combination, evidence-based therapies are the most effective strategy in HF.17 Replacing an ACE inhibitor with ARNI (sacubitril/valsartan) in combination therapy was associated with a greater reduction in CV mortality and HF hospitalisation (Figure 3).

via aggressive up-titration. High-intensity therapy was associated with a 34% relative reduction in the primary endpoint of HF readmission or all-cause death at 180 days This was driven by a 44% reduction HF readmission, a 26% reduction in CV death and a 16% reduction in all-cause death, compared to usual care. There was a slight increase in adverse effects in patients receiving high-intensity care, although there was no difference in serious adverse effects such as hypokalaemia and worsening renal function between the two groups.

The challenge is how to achieve this rapid up-titration of therapies once patients have been discharged. Dr Devlin introduced a novel algorithm for achieving HFrEF treatment targets within 3 months that involved up-titration of each therapy every 2 weeks:20

• Week 1 – Initiate ARNI + SGLT2 inhibitor

• Week 2 – Exercise and rehabilitation

• Week 3 – Initiate beta-blocker

• Week 4 – Exercise and rehabilitation

• Week 5 – Initiate MRA

Figure 3: Relative risk reduction for cardiovascular mortality or HF hospitalisation of different pharmacological treatment combinations. Adapted from Tromp et al (2022).17

Early initiation of optimal combination therapy is associated with significant reductions in HF mortality and hospitalisation. The accumulating evidence supporting combination therapy has resulted in the consensus recommendation to promote optimal care and minimise hospitalisations.1

An ARNI/ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor is recommended in all patients with HFrEF (Figure 4).

Euvolaemic

This novel approach resulted in a significant increase in the percentage of HF patients achieving maximally tolerated doses of all four classes of foundational therapies at 3 months (p<0.01).20

The involvement of pharmacists in optimising HF treatments is also helpful. One study evaluated the effectiveness of pharmacist-led HF clinics in optimising treatment for HFrEF patients.21 In 76 patients with 34% virtual consultations, pharmacist-led clinics resulted in a high uptake of optimally dosed, guidance-directed therapies as well as improvements in NT-pro BNP and LVEF.

CASE STUDY 1: 64-year-old male with decompensated HFrEF

Returning to this case study the recommended interventions included:

• A diuretic for symptoms.

• Switching cilazapril to sacubitril/valsartan after a 36-hour washout.

• The addition of spironolactone.

Diu r etic for symptoms of congestion

If LVEF ≤35% after 3 months: ICD and/or CRT (if QRS ≥130ms)

If SR ≥70 bpm + LVEF ≤35%: add ivabradine#

* ARNI preferred. ACE inhibitor can be considered as an alternative if problematic hypotension and consider switching to ARNI later. † Carvedilol, bisoprolol or metoprolol succinate recommended. ‡ Empagliflozin recommended. # Not funded for use in heart failure in New Zealand.

Figure 4: Treatment algorithm based on the presence or absence of clinical congestion. Adapted from Sindone et al (2022).18

Managing acute decompensated HF

Once again, Dr Devlin emphasised the importance of initiating all four foundational therapies as soon as possible in HF patients. In practice, this means that if a patient presents with acute decompensated HF, a small dose of all four therapies, i.e. an ARNI/ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor, is better than up-titrating one or two classes to maximum doses before adding additional therapies. A tailored approach to treatment can be considered to achieve this. For example, if the patient has tachycardia or AF, a beta-blocker can be added early and/or if renal dysfunction is present a SGLT2 inhibitor should be considered.

The STRONG-HF study demonstrated that patients who had been admitted to hospital with acute HF benefited from the rapid up-titration of guideline-directed therapy and that this approach was safe.19 The study randomised 1,078 patients to high-intensity or usual care prior to discharge. The intention of the high-intensity group was to achieve maximum-tolerated doses of guideline-directed therapy as quickly as possible

• Up-titration of metoprolol.

• Ideally, the addition of empagliflozin.

CASE STUDY 2: 71-year-old female with HFpEF

Medical History Investigations Medications

• Mild effort intolerance for 2-3 years, more pronounced recently

• No chest discomfort or palpitations

• T2D

• Hypertension

• Hyperlipidaemia

• GI reflux disease

• Overweight (BMI 27)

• BP 160/96 mmHg

• Heart rate 86/regular

• JVP +3 cm

• Bilateral pitting ankle oedema

• No sacral oedema

• Soft ESM, S4, no S3

• Occasional basal crackles

• Hb 118 g/dL

• eGFR 44 mL/min/m2

• HbA1c 57 mmol/mol

• NT-pro BNP 358 pmol/L

• LDLC 2.3 mmol/L

• Echocardiogram

- Normal LV size and contractility

- EF 54%

- Moderate LVH

- Dilated left atrium

- Impaired relaxation

- Aortic sclerosis

• Quinapril 20 mg/day

• Atorvastatin 40 mg/day

• Pantaprozole 20 mg nocte

• Metoprolol CR 47.5 mg/day

• Metformin 500 mg BD

The clinical picture for this patient was consistent with hypertensive heart disease with aortic sclerosis and the patient was diagnosed with HFpEF. The NT-pro BNP level was important in arriving at this diagnosis.

Heart Failure Management in 2023: Challenges and Opportunities

The clinical characteristics of the HF phenotypes are shown in Table 1. Dr Devlin noted that HFpEF results in significant morbidity in New Zealand communities and accounts for approximately 40% of acute HF hospital admissions.22

Table 1: Clinical characteristics of HF phenotypes. Adapted from Savarese et al (2022).23

Phenotype

Age

Women

Ischemic heart disease

Atrial fibrillation

Hypertension

Chronic kidney disease

Natriuretic peptide levels

HFpEF and HFmrEF management has changed

Prior to 2021, patients with HFpEF were investigated for significant coronary artery disease, treated to a target BP ≤120/80 mmHg (particularly if LVH is present), prescribed a diuretic for symptoms and the possibility of AF considered. Practice recommendations for patients with HFpEF and HFmrEF have recently changed, however, due to studies involving dapagliflozin (DAPA-HF) and empagliflozin (EMPEROR-Preserved).24,25 These studies showed a significant and comparable reduction in HF hospitalisations with SGLT2 inhibitors, which were well tolerated in patients with HFpEF and HFmrEF. Guidelines are likely to be updated worldwide following these studies.

Questions and answers

Dr Devlin provided the following answers to questions from the audience:

2023 management of patients with HFpEF and HFmrEF should include:

• Initiating an SGLT2 inhibitor.

• An ACE inhibitor/ARB for BP.

• Consider spironolactone.

• Consider switching to ARNI.

• Exclude ischaemia.

• Consider the possibility of AF.

CASE STUDY 2: 71-year-old female with HFpEF

Dr Devlin returned to case study two. The patient began treatment with:

• Empagliflozin 10 mg daily as she had T2D.

• Spironolactone 12.5 mg daily.

The possibility of ischaemic heart disease was investigated and excluded.

Dr Devlin finished his presentation with three key questions for all clinicians to ask on Monday:

• Are my patients with HF on optimal evidence-based care?

• Does this include an aldosterone antagonist and consideration of sacubitril/ valsartan?

• If the patient has T2D, are they eligible for an SGLT2 inhibitor?

1. In the experience of one attendee, many patients who have been discharged from hospital following an admission for acute HF are experiencing symptoms of postural hypotension. Is it possible that patients with NYHA II symptoms tolerate the combination of four recommended HF medicines better than patients with more advance HF, i.e. type IV? Symptomatic postural hypotension is an important limitation to optimisation of evidence-based care, particularly for patients with more advanced HF. When present, the need for other medications that lower blood pressure should be reviewed. For example, if a patient is taking 80 mg of frusemide and it is not possible to up-titrate sacubitrilvalsartan due to symptomatic postural hypotension, is it possible to consider reducing the dose of frusemide? Are there other medicines that can be reduced to reduce the symptoms of hypotension?

2. What is the next step if a patient becomes hyperkalemic on the foundational medicines?

Firstly, Dr Devlin would consider if there were other explanations for an elevated potassium level. Withholding spironolactone would be one possible strategy in this situation as well as being cautious when restarting it, e.g. spironolactone 12.5 mg every second day. If the patient’s renal function has declined significantly, it may be appropriate to also withhold the ACE inhibitor/ARB. Treatment needs to be individualised in this situation.

3. What is the role of NT-pro BNP for monitoring worsening HF?

In Dr Devlin’s opinion, NT-pro BNP is a useful test to firstly exclude HF. In his practice, he also finds NT-pro BNP helpful in optimising evidence-base care. Finally, if a patient with HF has had a stable NT-pro BNP but their level is now elevated, this should be cause for concern and potential reasons for the elevation investigated.

4. When is the best time to deprescribe frusemide given that long-term treatment is not recommended, but HF patients are often taking this medicine for years?

The ongoing need for medication needs to be constantly reviewed. In the case of frusemide, it does not make sense for an asymptomatic patient to continue treatment as there is no known prognostic benefit for HF patients to be taking frusemide, it is purely to treat symptoms. Also, as discussed previously, continuing diuretics in a patient with minimal symptoms may limit the ability to maximise treatments that improve outcomes.

REFERENCES

1. Ministry of Health. Annual Update of Key Results 2021/22: New Zealand Health Survey. www.health.govt.nz/publication/annual-update-key-results-2021-22-newzealand-health-survey

2. Ministry of Health. Publicly funded hospital discharges – 1 July 2017 to 30 June 2018. Published 2020. www.health.govt.nz/publication/publicly-funded-hospitaldischarges-1-july-2017-30-june-2018

3. Dickstein K, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J. 2008;29(19):2388-2442.

4. McMurray JJV, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33(14):1787-1847.

5. Okumura N, et al. Importance of Clinical Worsening of Heart Failure Treated in the Outpatient

Setting: Evidence From the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF). Circulation. 2016;133(23):2254-2262.

6. McDonagh TA, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42(36):3599-3726.

7. Ouwerkerk W, et al. Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study. Eur Heart J. 2017;38(24):1883-1890.

8. Pfeffer MA. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349(20):1893-1906.

9. Pitt B, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II. Lancet. 2000;355(9215):1582-1587.

10. Burnett H, et al. Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction: A Network Meta-Analysis. Circ Heart Fail. 2017;10(1):e003529.

11. Zannad F, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet 2020;396(10254):819-829.

12. McMurray JJV, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004.

13. Entresto®New Zealand Data Sheet. New Zealand data sheet. Published online 2020. www.medsafe.govt.nz/profs/datasheet/e/entrestotab.pdf (Accessed Jul, 2021)

14. Chandra A, et al. Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. 2018;3(6):498-505.

15. Velazquez EJ, et al. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med 2019;380(6):539-548.

16. Voors AA, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28(3):568-574.

17. Tromp J, et al. A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction. JACC Heart Fail 2022;10(2):73-84.

18. Sindone AP, De Pasquale C, Amerena J, et al. Consensus statement on the current pharmacological prevention and management of heart failure. Med J Aust 2022;217(4):212-217. doi:10.5694/mja2.51656

19. Mebazaa A, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, openlabel, randomised, trial. Lancet. 2022;400(10367):1938-1952.

20. Pandy A., et al. A novel algorithm for rapid sequence optimization of guideline directed medical therapy for heart failure with reduced ejection fraction. Eur Heart J 2022;43(S2).

21. Williams R, et al. Evaluation of a prescribing pharmacist-led heart failure (HF) up-titration clinic. Eur Heart J 2022;43(S2).

22. Fitzsimons S, et al. Relationship Between Soluble Transferrin Receptor and Clinical Outcomes in Patients With Heart Failure According to Ejection Fraction Phenotype: The New Zealand PEOPLE Study. J Card Fail. 2022;28(8):1255-1263.

23. Savarese G, et al. Heart failure with mid-range or mildly reduced ejection fraction. Nat Rev Cardiol. 2022;19(2):100-116.

24. Anker SD, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-1461.

25. Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387(12):10891098. doi:10.1056/NEJMoa2206286

This article was commissioned by Boehringer Ingelheim (NZ) Ltd and Eli Lilly (NZ ) Ltd. The content is entirely independent and based on studies and the author’s opinion. The views expressed do not necessarily reflect the views of Boehringer Ingelheim and Eli Lilly. Before prescribing any prescription medications mentioned in this article please consult the full data sheet. Treatment decisions based on these data are the full responsibility of the prescribing healthcare professional.

HfrEF HRmrEF HFpEF