Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

all patients

1st line – sodium-glucose cotransporter-2 (SGLT2) inhibitor

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ACUTE
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all patients
1st line – 

sodium-glucose cotransporter-2 (SGLT2) inhibitor

SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) are recommended for patients with HFpEF to decrease heart failure hospitalisations and cardiovascular mortality.[2][3][5]​​[87][88]

The EMPEROR-Preserved trial found that empagliflozin reduced the combined risk of cardiovascular death or hospitalisation for heart failure (HF) in patients with HFpEF, regardless of the presence or absence of diabetes, compared with placebo.[89][90][91]​​​​​ Patients who received empagliflozin also had an early and sustained reduction in risk and severity of a broad range of inpatient and outpatient events, such as a decrease in the need for hospitalisations requiring aggressive therapy, a decrease of worsening events requiring intensification of diuretics, and an increased likelihood of functional class improvement.[94]​ ​Health-related quality of life was also improved.[95] T​he effects were similar in women and men, and seen across a broad age spectrum.[96][97]​ The PRESERVED-HF trial compared dapagliflozin with placebo in patients with HFpEF and found that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations, and exercise function, and was well tolerated in chronic HFpEF.[99]​ The DELIVER trial found that dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction, both in those with and without history of recent heart failure hospitalisation, and across the spectrum of baseline kidney function and glycaemic range.[101][102][103][104][105][106][107]​ Prespecified analysis on outcomes according to frailty status found that improvements in symptoms, physical function, and quality of life were larger in patients with the greatest level of frailty.[114]​ The efficacy and safety of dapagliflozin was also found to be consistent across the spectrum of body mass index, with a larger absolute effect seen in patients with obesity.[115]

Primary options

dapagliflozin: 10 mg orally once daily in the morning

OR

empagliflozin: 10 mg orally once daily in the morning

Plus – lifestyle measures

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ACUTE
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all patients
Plus – 

lifestyle measures

Treatment recommended for ALL patients in selected patient group

Lifestyle changes, dietary and nutritional modifications, exercise training, and health maintenance have the potential to reduce heart failure progression.[77]​

Weight loss should be promoted in patients who are overweight.

Exercise training or regular physical activity is recommended to improve function and quality of life.[3][78]​​​​​[79][80][81]​​​​​​​ Cardiac rehabilitation, which includes medical evaluation, education on adherence to medication, advice on diet, psychosocial support, and an exercise training and physical activity programme can also be recommended to improve function, exercise tolerance, and quality of life. US guidelines advise that patients who are on optimal guideline-directed medical treatment for HF, in stable medical condition, and able to participate in an exercise programme are candidates for an exercise rehabilitation programme.[3] ​There is developing evidence to support home-based cardiac rehabilitation alternatives to centre-based programmes.[82][83][84]

Dietary sodium intake is an easily modifiable factor. There is limited evidence for sodium restriction in patients with heart failure; however, guidelines recommend that excessive sodium intake should be avoided.[3][4]​​[86]​​​​

Tobacco and alcohol discontinuation should be encouraged.

Consider – diuretic

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ACUTE
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all patients
Consider – 

diuretic

Additional treatment recommended for SOME patients in selected patient group

All patients with signs of congestion should receive diuretics to relieve symptoms and prevent worsening heart failure.[2][3][4]​​[5]​​​​​​​​​

Loop diuretics are the preferred diuretic for use in most patients with heart failure. In patients with comorbid hypertension, and only mild fluid retention, a thiazide diuretic may be preferred because they confer more persistent antihypertensive effects.[3]​

Loop diuretics used for the treatment of heart failure and congestion include furosemide, bumetanide, and torasemide. The most commonly used agent appears to be furosemide, but some patients may respond more favourably to another loop diuretic. In treatment resistance, loop diuretics should be combined with a thiazide diuretic (e.g., chlorothiazide, hydrochlorothiazide) or a thiazide-like diuretic (e.g., metolazone, indapamide).

Careful monitoring of renal function and electrolytes is essential. The minimum dose of diuretic should be used to relieve congestion, keep the patient asymptomatic, and maintain a dry weight. Some patients may be able to come off the diuretics completely, but they need very close long-term follow-up.

Primary options

furosemide: 20-40 mg intravenously/intramuscularly initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg/dose increments every 6-8 hours according to response, maximum 600 mg/day

OR

bumetanide: 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours according to response, maximum 10 mg/day; 0.5 to 2 mg orally once daily initially, may repeat every 4-5 hours until response, maximum 10 mg/day

OR

torasemide: 5-20 mg orally once daily initially, increase dose gradually according to response, maximum 40 mg/day

OR

chlorothiazide: 500-1000 mg orally once or twice daily

OR

hydrochlorothiazide: 25-200 mg orally once daily

OR

indapamide: 2.5 to 5 mg orally once daily

OR

metolazone: 5-20 mg orally once daily

Consider – aldosterone antagonist

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ACUTE
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all patients
Consider – 

aldosterone antagonist

Additional treatment recommended for SOME patients in selected patient group

US guidelines recommend that aldosterone antagonists (e.g., spironolactone, eplerenone) should be considered in patients with HFpEF with and without congestion, particularly among those with lower left ventricular ejection fraction (LVEF).[2][3]​​​

For patients with HFpEF and congestion, an aldosterone antagonist (e.g., spironolactone, eplerenone) can be started upfront with or without a loop diuretic.[11]

European guidelines make no recommendation for aldosterone antagonists in HFpEF.

One Cochrane review found that aldosterone antagonists in HFpEF have a modest beneficial effect in reducing heart failure hospitalisation, but probably have little or no effect on cardiovascular mortality and quality of life.[123]​

The TOPCAT trial compared spironolactone with placebo in patients with HFpEF (EF 45% or more) and found no significant difference in the primary end point, a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalisation for heart failure.[124]​ The trial included participants in the US, Canada, Brazil, Argentina, Russia, and Georgia. Post-hoc analysis suggested that there were clinical benefits with spironolactone in patients with HFpEF from the Americas, with a significant reduction in the primary end point. In Russia and Georgia, all clinical event rates were markedly lower, and there was no detectable impact of spironolactone on any outcomes.[125]​ Further post-hoc analysis by ejection fraction showed the potential efficacy of spironolactone was greatest at the lower end of the LVEF spectrum.[126]

Spironolactone and eplerenone can both cause hyperkalaemia, and precautions should be taken to minimise the risk; regular monitoring of serum potassium and renal function is recommended.[3] Use of aldosterone antagonists and angiotensin-II receptor antagonists together may increase the risk of hyperkalaemia, especially in older patients or patients with renal impairment.

Primary options

spironolactone: 12.5 to 50 mg orally once daily

OR

eplerenone: 25-50 mg orally once daily

Consider – angiotensin receptor-neprilysin inhibitor (ARNi)

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all patients
Consider – 

angiotensin receptor-neprilysin inhibitor (ARNi)

Additional treatment recommended for SOME patients in selected patient group

US guidelines recommend that sacubitril/valsartan may be considered for selected patients with HFpEF, particularly among those with lower LVEF.[2][3]​​

European guidelines make no recommendation for sacubitril/valsartan in HFpEF.

One Cochrane review found that ARNi treatment in HFpEF has a modest beneficial effect in reducing heart failure hospitalisation, but probably has little or no effect on cardiovascular mortality and quality of life.[123]

The PARAGON-HF trial compared sacubitril/valsartan with valsartan alone in patients with HFpEF (EF 45% or more) and found that sacubitril/valsartan did not achieve a significant reduction in the primary composite end point of cardiovascular death or total (first and recurrent) heart failure hospitalisations.[127]​ In pre-specified subgroup analyses, sacubitril/valsartan was shown to be beneficial in reducing hospitalisation patients at the lower end of the LVEF spectrum and in women.[127][128]​​​

The PARALLAX trial compared sacubitril/valsartan with standard medical therapy (enalapril, valsartan, or placebo) in patients with HFpEF (EF 40% or more) and found sacubitril/valsartan significantly decreased plasma NT-pro-BNP concentration at 12 weeks, but did not improve submaximal exercise capacity.[129]

Primary options

sacubitril/valsartan: treatment-naive or treatment-experienced on a low dose: 24 mg (sacubitril)/26 mg (valsartan) orally twice daily initially, increase gradually according to response, maximum 97 mg (sacubitril)/103 mg (valsartan) twice daily; treatment-experienced on a usual dose: 49 mg (sacubitril)/51 mg (valsartan) orally twice daily initially, increase gradually according to response, maximum 97 mg (sacubitril)/103 mg (valsartan) twice daily

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Consider – angiotensin-II receptor antagonist

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ACUTE
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all patients
Consider – 

angiotensin-II receptor antagonist

Additional treatment recommended for SOME patients in selected patient group

US guidelines recommend that angiotensin-II receptor antagonists may be considered for selected patients with HFpEF, particularly among those with lower LVEF.[2][3]​​​

European guidelines make no recommendation for angiotensin-II receptor antagonists in HFpEF.

One Cochrane review found there was no evidence supporting an important beneficial effect of angiotensin-II receptor antagonists on mortality and hospitalisation outcomes in patients with HFpEF and that their use in HFpEF in the absence of an alternative indication is not supported.[123]​

In the CHARM-preserved trial, candesartan was compared with placebo in patients with HFpEF (EF 40% or more) but there was no significant difference in the primary end point of cardiovascular death or heart failure hospitalisation) between the two groups.[130] Post-hoc analysis showed the potential efficacy of candesartan was greatest at the lower end of the LVEF spectrum.[126]​ 

Primary options

candesartan: 4-32 mg orally once daily

OR

losartan: 25-150 mg orally once daily

OR

valsartan: 40-160 mg orally twice daily

Consider – rate and rhythm control + anticoagulation

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ACUTE
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all patients
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with atrial fibrillation (AF)
Consider – 

rate and rhythm control + anticoagulation

Additional treatment recommended for SOME patients in selected patient group

AF and HF may cause or exacerbate each other and the relationship is complex.

HF therapies should be optimised. Treatment of AF involves correction of the abnormal rate/rhythm, along with anticoagulation. Options for rate and rhythm control are determined by the presence of HF and extent of LV dysfunction.[3][4]

See Established atrial fibrillation.

Consider – weight loss programme

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ACUTE
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all patients
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with obesity
Consider – 

weight loss programme

Additional treatment recommended for SOME patients in selected patient group

Pharmacotherapy with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to improve patient-oriented quality of life outcomes (measured by Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score [KCCQ-CSS] and 6-minute walk distance at 52 weeks) in patients with obesity and HFpEF and results in greater weight loss compared with placebo.[135]​ In semaglutide-treated patients, the improvements in quality of life outcomes were greater with larger body weight reduction.[136]

Surgically induced weight loss in individuals with class III obesity (body mass index [BMI] 40 or above) has been shown to reverse left ventricular (LV) hypertrophy and restore diastolic function.[52][131]

See Obesity in adults.

Plus – treatment of hyperglycaemia

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ACUTE
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all patients
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with diabetes
Plus – 

treatment of hyperglycaemia

Treatment recommended for ALL patients in selected patient group

Treatment of HFpEF is similar in patients with and without diabetes.

SGLT2 inhibitors are recommended as first-line treatment of hyperglycaemia in patients with type 2 diabetes and HF to reduce HF-related morbidity and mortality.[3][4]

See Overview of diabetes.

Consider – finerenone

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ACUTE
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all patients
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with diabetes
Consider – 

finerenone

Additional treatment recommended for SOME patients in selected patient group

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, is recommended for the prevention of HF hospitalisation in patients with chronic kidney disease and type 2 diabetes.[5]

Primary options

finerenone: 20 mg orally once daily

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Consider – surgical revascularisation

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ACUTE
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all patients
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with chronic coronary disease
Consider – 

surgical revascularisation

Additional treatment recommended for SOME patients in selected patient group

Revascularisation in those with HFpEF and coronary artery disease has been associated with less deterioration of LV function and improved outcomes; however, prospective trials are needed to determine optimal treatment of these patients.[2]

See Chronic coronary disease.

Consider – assessment and treatment of sleep apnoea

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ACUTE
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all patients
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with daytime sleepiness
Consider – 

assessment and treatment of sleep apnoea

Additional treatment recommended for SOME patients in selected patient group

Patients with HF and daytime sleepiness may have sleep studies to assess for obstructive sleep apnoea and central sleep apnoea.[3][4]

In patients with HF and obstructive sleep apnoea, continuous positive airway pressure is recommended to improve sleep quality and reduce daytime sleepiness, however it does not seem to reduce mortality.[3][4]

See Obstructive sleep apnoea, and Central sleep apnoea.

Consider – supportive measures +/- nephrology referral

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ACUTE
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all patients
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with chronic kidney disease
Consider – 

supportive measures +/- nephrology referral

Additional treatment recommended for SOME patients in selected patient group

Some drugs used in the management of HF should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information.

Most patients will tolerate mild-to-moderate degrees of functional renal impairment without difficulty. Initiation of guideline directed-medical therapy (GDMT) for HF with a SGLT2 inhibitor, ARNi, or angiotensin-II receptor antagonist may result in an initial rise in serum creatinine and a drop in estimated glomerular filtration rate (eGFR), but this change is generally transient and should not be a reason for discontinuation.[2][4]

An increase in serum creatinine of <50% above baseline, up to 3 mg/dL, or a decrease in eGFR of <10% from baseline, as long as eGFR is >25 mL/min/1.73 m², may be considered as acceptable.

If the serum creatinine increases to >3 mg/dL, the renal insufficiency can severely limit the efficacy and enhance the toxicity of established treatments.[133][134]

Aldosterone antagonists should be used with caution in patients with CKD and hyperkalaemia. The US guidelines advise that they are only initiated in patients with eGFR >30mL/min/1.73m² and serum potassium <5.0 mEq/L.[3]

Consultation with a nephrology consultant should be considered.

See Chronic kidney disease.

Consider – lipid-lowering therapy

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ACUTE
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all patients
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with hyperlipidaemia
Consider – 

lipid-lowering therapy

Additional treatment recommended for SOME patients in selected patient group

All patients with HFpEF and hyperlipidaemia will need lifestyle modifications and most will also require treatment with a statin possibly with additional non-statin lipid-lowering therapy.

For details of management of HF with hypercholesterolaemia, see Hypercholesterolaemia.

Consider – referral to endocrinologist

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ACUTE
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all patients
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with thyroid disorder
Consider – 

referral to endocrinologist

Additional treatment recommended for SOME patients in selected patient group

Both hypo- and hyperthyroidism are associated with HF and assessment of thyroid function is recommended.

Thyroid disorders are treated as per endocrinology guidelines; referral to endocrinologist should be considered.

See Overview of thyroid disorders.

Plus – interventions to improve HF self-care

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ACUTE
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all patients
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with depression
Plus – 

interventions to improve HF self-care

Treatment recommended for ALL patients in selected patient group

Depression is common in patients with HF and is associated with a reduced quality of life and increased mortality.

Treatment with conventional therapies (e.g., antidepressants) does not seem to directly improve these outcomes. However, interventions that focus on improving HF self-care (e.g., psychotherapy, selective serotonin-reuptake inhibitors [SSRIs], or nurse-led support) may reduce hospitalisation and mortality in patients with moderate or severe depression.[3][4]

See Depression in adults.

Plus – multidisciplinary team management

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all patients
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comorbid cancer
Plus – 

multidisciplinary team management

Treatment recommended for ALL patients in selected patient group

Patients who develop HF and/or depressed LV systolic function secondary to cancer therapy should be treated with GDMT. Generally, GDMT should not be discontinued unless there are specific and compelling reasons to hold these medicines and this should be managed by a multidisciplinary team.

Before starting any cardiotoxic cancer therapy baseline cardiac function should be measured and ongoing monitoring after completion of a course of chemotherapy may be helpful for risk stratification.[3][4]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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