HFrEF: A Challenge We Can Overcome

Guideline-Directed Medical Therapy (GDMT) is transforming the management of Heart Failure with Reduced Ejection Fraction, offering a proven roadmap to improve patient outcomes — yet adoption remains suboptimal.

Ref: JAMA Cardiol. 2024;9(4):397–404

Heart Failure Management Illustration
Heart Failure Overview Icon

Understanding HFrEF

Heart Failure with Reduced Ejection Fraction (HFrEF) is a complex condition associated with high morbidity and mortality. Despite the availability of effective therapies, patient outcomes remain suboptimal when guideline-directed medical treatments are not initiated early and comprehensively.

GDMT: The Foundation of HFrEF Management

Optimal GDMT can reduce mortality by over 70% while significantly improving quality of life in patients with HFrEF.

ARNI ACEi ARB Icon

ARNI / ACEi / ARB

Angiotensin pathway modulators for cardiac remodeling

Beta Blockers Icon

Beta-Blockers

Reduce heart rate and improve cardiac function

MRA Icon

MRA

Mineralocorticoid Receptor Antagonists

SGLT2 Inhibitors Icon

SGLT-2 Inhibitors

Newest pillar with proven mortality benefits

First-line GDMT therapies carry Class I recommendations in the 2022 AHA/ACC/HFSA guidelines for HFrEF.

Rapid Evidence-Based Sequencing of Foundational Therapies

Simultaneous or rapid sequence initiation of GDMT enables earlier clinical benefit compared to conventional stepwise escalation.

Conventional Sequencing

  • ACE inhibitor or angiotensin receptor blocker
  • Beta-Blocker
  • Mineralocorticoid receptor antagonist
  • Angiotensin receptor neprilysin inhibitor
  • SGLT2 inhibitor

Note: Up titration to target doses at each step Typically requires 6 months or more

Rapid Sequencing

  • Beta-blocker+SGLT2 inhibitor
  • Angiotensin receptor neprilysin inhibitor
  • Mineralocorticoid receptor antagonist

Note: All 3 step achieved within 4 weeks Up titration to target doses thereafter

All foundational therapies can be initiated within 4 weeks, followed by up-titration to target doses thereafter.

Elevate Heart Failure Treatment with GDMT

Sacubitril / Valsartan

Redefines neurohormonal modulation in heart failure and reduces the risk of cardiovascular death and hospitalization in patients with chronic Heart Failure with Reduced Ejection Fraction (HFrEF).

Sacubitril Valsartan Tablets

Dapagliflozin

Provides cardiorenal protection and reduces the risk of cardiovascular death and heart failure hospitalization in patients with heart failure.

Dapagliflozin Tablets

Evidence from Landmark Clinical Trials

PARADIGM-HF Trial

0%

Reduction in cardiovascular death or heart failure hospitalization compared to enalapril in patients with HFrEF.

DAPA-HF Trial

0%

Reduction in the composite risk of cardiovascular death or worsening heart failure.

Benefits observed even in patients already receiving mineralocorticoid receptor antagonists and beta-blockers.

Being Smart, Beyond Glycaemic Control

Glycaemic Control Icon

Improved glycaemic control

Blood Pressure Reduction Icon

Reduction in blood pressure

Weight Reduction Icon

Weight reduction

Reduced Hospitalization Icon

Reduced hospitalization due to heart failure

Dosage and Indications

Indications

  • To reduce the risk of cardiovascular death and hospitalization for heart failure in adults with chronic heart failure.
  • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors.
  • To reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure with reduced ejection fraction.

Adult Dosage

Sacubitril / Valsartan: Recommended starting dose is one tablet of 49 mg / 51 mg twice daily. The dose should be doubled after 2–4 weeks to the target dose of 97 mg / 103 mg twice daily, as tolerated by the patient.

Dapagliflozin: Recommended dose is 10 mg once daily for heart failure. For type 2 diabetes mellitus, treatment may be initiated at 5 mg once daily and increased to 10 mg once daily if additional glycaemic control is required.

Pediatric Dosage (Heart Failure)

  • Patients ≤ 40 kg: Weight-based dosing as per clinical guidance.
  • Patients 40 kg to 50 kg: Gradual up-titration based on tolerance.
  • Patients ≥ 50 kg: Dosing similar to adult regimen.

Renal Function Considerations

Renal function should be assessed prior to initiation of therapy and monitored periodically. Dapagliflozin is not recommended for glycaemic control in patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m².

Abridged Prescribing Information

Contraindications

  • Hypersensitivity to the active substances or to any excipients.
  • History of angioedema related to previous ACE inhibitor or ARB therapy.
  • Concomitant use with aliskiren in patients with diabetes mellitus.
  • Severe hepatic impairment or biliary cirrhosis.

Warnings and Precautions

  • Risk of hypotension, especially in volume-depleted patients.
  • Renal function should be monitored periodically.
  • May increase the risk of hyperkalaemia.
  • Not recommended during pregnancy.

Adverse Effects

  • Hypotension
  • Hyperkalaemia
  • Renal impairment
  • Dizziness

Drug Interactions

  • ACE inhibitors and other ARBs.
  • Potassium-sparing diuretics or supplements.
  • NSAIDs may reduce therapeutic effect.
  • Concomitant use with lithium may increase toxicity.