Dapagliflozin, known by its brand name Farxiga, is a medication for a specific type of heart failure: Heart Failure with Preserved Ejection Fraction (HFpEF). This condition has historically been challenging to manage, and dapagliflozin offers a new approach for patients. It represents a shift in therapy by targeting underlying issues related to fluid balance and heart function.
What is Heart Failure with Preserved Ejection Fraction (HFpEF)?
Heart Failure with Preserved Ejection Fraction (HFpEF) is a complex condition accounting for at least half of all heart failure diagnoses. In HFpEF, the heart’s main pumping chambers, the ventricles, become stiff. This stiffness prevents the ventricles from relaxing properly between beats, meaning they cannot fill with an adequate amount of blood.
The term “preserved ejection fraction” refers to the fact that the heart muscle can still pump out the blood it contains, with a left ventricular ejection fraction (LVEF) of 50% or more. The problem isn’t the pumping action itself, but rather the filling phase, known as diastole. This is the primary distinction from another common type of heart failure, Heart Failure with Reduced Ejection Fraction (HFrEF), where the heart muscle is weakened and cannot pump blood effectively, resulting in an LVEF of 40% or less.
Because the stiff heart in HFpEF cannot fill efficiently, pressure builds up inside the heart’s chambers. This increased pressure can back up into the lungs, causing symptoms like shortness of breath and fatigue, especially during physical activity. The condition is most common in older individuals, particularly women, and is frequently associated with risk factors like hypertension, obesity, and diabetes.
How Dapagliflozin Treats HFpEF
Dapagliflozin belongs to a class of drugs called sodium-glucose cotransporter 2 (SGLT2) inhibitors. These medications were originally developed to treat type 2 diabetes. Their primary function is to block the SGLT2 protein in the kidneys, which prevents the reabsorption of glucose into the bloodstream and causes it to be passed out of the body through urine. This process not only lowers blood sugar but also has beneficial effects for patients with HFpEF, regardless of whether they have diabetes.
A primary action of dapagliflozin in treating HFpEF is its diuretic, or fluid-clearing, effect. By promoting the removal of glucose in the urine, it also pulls excess sodium and water out of the body. This reduction in overall fluid volume lowers blood pressure and decreases the amount of blood returning to the heart, which lessens the workload on the already strained, stiff ventricles. This helps to alleviate the high filling pressures that are a fundamental problem in HFpEF.
Beyond its diuretic properties, dapagliflozin appears to have direct protective effects on the heart and blood vessels. Research suggests it may improve the metabolism and energy efficiency of the heart muscle itself. The medication has also been shown to reduce inflammation and oxidative stress, which are thought to contribute to the ventricular stiffness seen in HFpEF.
Evidence from Clinical Trials
The effectiveness of dapagliflozin for treating HFpEF was solidified by a major international study called the DELIVER clinical trial. The study enrolled 6,263 patients who had heart failure with a left ventricular ejection fraction greater than 40%, which includes those with HFpEF and a related condition, Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF).
The study’s main goal was to track the combined rate of either worsening heart failure (requiring hospitalization or an urgent clinic visit) or death from cardiovascular causes. Over a median follow-up of 2.3 years, patients taking dapagliflozin had an 18% lower risk of reaching this primary endpoint compared to those taking a placebo. This benefit was consistent across different patient groups, including those with and without diabetes.
The trial also showed that patients treated with dapagliflozin reported fewer symptoms and had a better quality of life. These findings established dapagliflozin as a foundational therapy for HFpEF, as very few treatments had previously shown a clear benefit for this patient population.
Potential Side Effects and Risks
While dapagliflozin is an effective treatment, it is associated with certain side effects and risks. The most common side effects are related to its mechanism of action, which increases sugar in the urine. This can lead to a higher incidence of genital yeast infections in both men and women, as well as an increased risk of urinary tract infections (UTIs).
Rare but more serious risks also exist. One is diabetic ketoacidosis (DKA), a condition where the body produces high levels of blood acids called ketones. DKA can occur even with normal or only slightly elevated blood sugar levels. Another very rare but serious infection is Fournier’s gangrene, a severe infection of the genital area. Patients should seek immediate medical attention if they experience symptoms like unusual pain, tenderness, or swelling in the genital region, accompanied by fever.
Certain individuals should use dapagliflozin with caution or may not be suitable candidates for the drug. This includes people with severe kidney disease, as the drug’s effectiveness depends on kidney function. The medication can also enhance the effect of diuretics, increasing the risk of dehydration and low blood pressure, so doses of other medications may need adjustment. Patients on a very low-carbohydrate or ketogenic diet may also have a higher risk of DKA.