What is the dosing of Empagliflozin (Empagliflozin) for Heart Failure with Preserved Ejection Fraction (HFpEF)?

From the Guidelines

Empagliflozin for heart failure with preserved ejection fraction (HFpEF) is typically dosed at 10 mg once daily taken orally, as established in the EMPEROR-Preserved trial, which demonstrated significant benefits in reducing cardiovascular death and heart failure hospitalizations in HFpEF patients 1. This dosage has been shown to reduce the primary composite endpoint of time to HF hospitalization or cardiovascular death by 21%, with a significant 29% reduction in time to HF hospitalization, and also resulted in a significant reduction in total HF hospitalizations, decrease in the slope of the eGFR decline, and a modest improvement in QOL at 52 weeks 1. The benefit of empagliflozin was similar irrespective of the presence or absence of diabetes at baseline, and no dose titration is required when starting empagliflozin for HFpEF, unlike some other heart failure medications 1. Some key points to consider when prescribing empagliflozin for HFpEF include:

• Patients should take it in the morning with or without food
• Renal function should be assessed before starting therapy, with dose adjustments generally not needed for mild renal impairment, but caution is advised if eGFR falls below 30 mL/min/1.73m²
• Patients should be monitored for potential side effects including genital mycotic infections, urinary tract infections, and volume depletion
• The medication works by inhibiting sodium-glucose cotransporter-2 (SGLT2) in the kidneys, promoting glucose excretion and sodium loss, which reduces cardiac preload and afterload, decreases myocardial oxygen demand, and improves cardiac efficiency through multiple mechanisms beyond glycemic control 1. It's also important to note that the optimal blood pressure goal and antihypertensive regimens are not known for patients with HFpEF, and RAAS antagonists including ACEi, ARB, MRA, and possibly ARNi, could be first-line agents given experience with their use in HFpEF trials 1. In terms of specific dosing, the starting and target doses of empagliflozin for HFpEF are 10 mg daily, with no need for dose titration 1. Overall, empagliflozin is a valuable treatment option for patients with HFpEF, and its use should be considered in conjunction with other evidence-based therapies to optimize patient outcomes.

From the Research

Empagliflozin Dosing for Heart Failure with Preserved Ejection Fraction (HFpEF)

• The recommended dosing of empagliflozin for HFpEF is 10 mg once daily, as stated in the EMPEROR-Preserved trial 2, 3.
• This dosing has been shown to reduce the risk of cardiovascular death or hospitalization for heart failure in patients with HFpEF, regardless of the presence or absence of diabetes 3.
• The efficacy of empagliflozin in HFpEF patients has been demonstrated across different subgroups, including those with and without atrial fibrillation 4, and those with varying degrees of frailty 5.

Efficacy of Empagliflozin in HFpEF

• Empagliflozin has been shown to reduce the combined risk of cardiovascular death or hospitalization for heart failure in HFpEF patients, with a hazard ratio of 0.79 (95% CI, 0.69-0.90) compared to placebo 3.
• The drug has also been shown to reduce the total number of hospitalizations for heart failure, with a hazard ratio of 0.73 (95% CI, 0.61-0.88) compared to placebo 3.
• Empagliflozin has been demonstrated to improve clinical outcomes and health-related quality of life in HFpEF patients, regardless of frailty status 5.

Safety and Tolerability of Empagliflozin in HFpEF

• Empagliflozin has been shown to be generally well-tolerated in HFpEF patients, with a similar safety profile to placebo 4, 3.
• The most common adverse events reported with empagliflozin in HFpEF patients include uncomplicated genital and urinary tract infections, and hypotension 3.