Is dapagliflozin (SGLT2 inhibitor) contraindicated in acute exacerbation of heart failure?

From the Guidelines

Dapagliflozin is not contraindicated in acute exacerbation of heart failure and may be beneficial in this setting, as evidenced by the DAPA-HF trial which showed a lower risk of worsening heart failure and cardiovascular death with dapagliflozin treatment 1.

Key Considerations

• The standard dose of dapagliflozin is 10 mg once daily, taken orally with or without food.
• When starting dapagliflozin during heart failure exacerbation, it is crucial to monitor fluid status, kidney function, and blood pressure closely due to the medication's diuretic effects.
• Patients should be euvolemic or hypervolemic before initiation to avoid volume depletion.
• Temporary discontinuation may be necessary if the patient develops significant hypotension, acute kidney injury, or is unable to maintain oral intake.

Mechanism and Benefits

• Dapagliflozin works by inhibiting sodium-glucose cotransporter-2 in the kidneys, promoting glucose excretion and sodium loss.
• This mechanism reduces cardiac preload and afterload while improving cardiac metabolism, providing cardiovascular benefits beyond glycemic control.
• The medication is valuable in heart failure management regardless of diabetes status, as shown by the EMPEROR-Reduced and DELIVER trials 1.

Clinical Judgment and Long-term Management

• Clinical judgment is important when initiating dapagliflozin during an acute episode.
• Once the patient is stabilized, dapagliflozin can typically be continued as part of the long-term heart failure management strategy.
• The use of SGLT2 inhibitors, including dapagliflozin, has been associated with a reduced risk of hospitalization for heart failure and cardiovascular death in patients with heart failure, as demonstrated by the EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58 trials 1.

From the FDA Drug Label

CONTRAINDICATIONS • History of serious hypersensitivity reaction to dapagliflozin or any of the excipients in DAPAGLIFLOZIN TABLETS (4)

DOSAGE AND ADMINISTRATION • Assess renal function prior to initiation and then as clinically indicated. Assess volume status and correct volume depletion before initiating. (2. 1)

The FDA drug label does not explicitly state that dapagliflozin is contraindicated in acute exacerbation of heart failure. However, it recommends assessing volume status and correcting volume depletion before initiating dapagliflozin, which may be relevant in the context of acute heart failure exacerbation.

• Key consideration: Assess volume status and correct volume depletion before initiating dapagliflozin.
• Clinical decision: Dapagliflozin is not directly contraindicated in acute exacerbation of heart failure, but caution is advised, and volume status should be assessed and corrected before initiation 2.

From the Research

Dapagliflozin in Acute Exacerbation of Heart Failure

• Dapagliflozin, an SGLT2 inhibitor, has been studied in the context of acute heart failure (AHF) and its potential benefits and risks in this setting 3, 4.
• A study published in the Journal of the American College of Cardiology found that early initiation of dapagliflozin in AHF was safe and associated with reduced loop diuretic doses and fewer intravenous diuretic up-titrations 3.
• Another study published in Kardiologiia found that dapagliflozin treatment in acute decompensated heart failure was associated with more pronounced body weight loss and lower average doses of loop diuretics, with no associated clinically significant impairment of renal function 4.

Safety and Efficacy

• The safety and efficacy of dapagliflozin in patients with heart failure have been evaluated in several studies, including a meta-analysis published in the American Journal of Cardiovascular Drugs, which found that dapagliflozin was associated with a significantly lower incidence of hospitalization for heart failure, all-cause mortality, cardiovascular death, and major adverse cardiovascular events 5.
• A study published in the Journal of the American College of Cardiology found that dapagliflozin was effective in reducing the risk of worsening heart failure or cardiovascular death in patients with heart failure and a left ventricular ejection fraction of more than 40% 6.
• Another study published in the Journal of the American College of Cardiology found that continuation of dapagliflozin treatment in patients with heart failure experiencing deterioration of kidney function was associated with a lower risk of cardiovascular outcomes and no excess in safety outcomes 7.

Contraindications

• Based on the available evidence, dapagliflozin is not contraindicated in acute exacerbation of heart failure 3, 4.
• In fact, the studies suggest that dapagliflozin may be beneficial in this setting, with improvements in diuretic efficiency, reduced loop diuretic doses, and fewer intravenous diuretic up-titrations 3, 4.