Does preserved heart failure respond to Farxiga (dapagliflozin)?

From the Guidelines

Farxiga (dapagliflozin) is a recommended treatment for patients with heart failure with preserved ejection fraction (HFpEF), as it has been shown to reduce the risk of worsening heart failure or cardiovascular death, improve quality of life, and decrease hospitalizations for heart failure. The most recent and highest quality study, the DELIVER trial 1, demonstrated the efficacy of dapagliflozin in patients with HFpEF, regardless of ejection fraction or diabetes status. The typical dose is 10 mg once daily, taken orally.

Key benefits of Farxiga for patients with HFpEF include:

• Reduced hospitalizations for heart failure
• Improved quality of life
• Decreased cardiovascular mortality
• Inhibition of sodium-glucose cotransporter-2 (SGLT2) in the kidneys, leading to increased glucose excretion in urine and beneficial effects on cardiac function, including reduced preload and afterload, improved ventricular filling, and decreased myocardial oxygen demand.

When prescribing Farxiga, it is essential to monitor patients for potential side effects, such as:

• Genital mycotic infections
• Urinary tract infections
• Volume depletion, especially when starting treatment Additionally, kidney function should be assessed before initiating therapy, as dose adjustments may be needed for those with severe renal impairment 1.

From the FDA Drug Label

Dapagliflozin reduced the incidence of the composite endpoint of CV death or hospitalization for heart failure [HR 0.71 (95% CI 0.55,0.92), p=0.0089] and all-cause mortality [HR 0.69 (95% CI 0.53,0.88), p=0. 0035]. Hospitalization for Heart Failure 37 (0.8) 71 (1.6) 0.51(0.34,0.76) The efficacy and safety of dapagliflozin 10 mg were assessed independently in two Phase 3 trials in adult patients with heart failure Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF, NCT03036124) was an international, multicenter, randomized, double-blind, placebo-controlled trial in patients with heart failure [New York Heart Association (NYHA) functional class II-IV] with reduced ejection fraction [left ventricular ejection fraction (LVEF) 40% or less]

Key Points:

• Dapagliflozin reduces the incidence of hospitalization for heart failure.
• The hazard ratio for hospitalization for heart failure is 0.51 (95% CI 0.34,0.76).
• Dapagliflozin is effective in patients with heart failure, including those with reduced ejection fraction.
• Preserved heart failure is not explicitly mentioned in the provided text, but the results from the DAPA-HF trial suggest that dapagliflozin may be beneficial for patients with heart failure, regardless of ejection fraction. 2

From the Research

Heart Failure and Farxiga

• Heart failure with preserved ejection fraction (HFpEF) is a condition where the heart's ejection fraction is normal, but the heart is still not functioning properly 3, 4, 5.
• Farxiga (dapagliflozin) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has been shown to be effective in reducing the risk of heart failure hospitalization or cardiovascular death in patients with HFpEF 3, 6.
• The use of SGLT2 inhibitors, such as dapagliflozin, is recommended as first-line pharmacologic therapy for HFpEF, in addition to lifestyle interventions such as exercise training and diet-induced weight loss 3, 5.

Mechanism of Action

• Dapagliflozin works by competitively binding to renal SGLT2 cotransporters, preventing glucose and sodium reabsorption, and leading to glucosuria 6.
• This mechanism of action has been shown to be effective in improving glycemic control without the risk of hypoglycemia, and also has benefits in cardiac and renal diseases 6.

Clinical Trials and Evidence

• Clinical trials have demonstrated the efficacy of dapagliflozin in reducing the risk of heart failure hospitalization or cardiovascular death in patients with HFpEF 3, 6.
• The DAPA-HF trial showed that dapagliflozin reduced the risk of worsening heart failure or cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF) 7.
• The DECLARE-TIMI 58 trial showed that dapagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure in patients with type 2 diabetes mellitus (T2DM) who had or were at risk for atherosclerotic cardiovascular disease 7.