Data Show Empagliflozin as Only Heart Failure Therapy to Demonstrate Risk Reduction in Patients With Cardiovascular Conditions

A pair of recent clinical trials found that empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) tablets are the first and only heart failure (HF) therapy to demonstrate a statistically significant risk reduction in cardiovascular death and hypertensive HF, regardless of left ventricle ejection fraction, according to a session at the American College of Cardiology (ACC) 2022 Scientific Sessions.

Javed Butler, MD, MPH, MBA, chair of the Department of Medicine at University of Mississippi Medical Center in Jackson, Mississippi, discussed 2 major clinical trials, Emperor-Preserved and Emperor-Reduced, which demonstrated nearly identical results in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) areas.

Empagliflozin is a once daily oral medication that can be taken in the morning with or without food at a starting dose of 10 mg, which is also the target dose. Further, it can be used with or without other common HF therapies with close monitoring in case any severe adverse effects (AEs) occur, according to Butler.

Empaglizflozin’s current indications include:

• Reducing the risk of cardiovascular death and hospitalization for HF in adults with heart failure.
• Reducing the risk of cardiovascular death in adults with type 2 diabetes (T2D) and established cardiovascular disease.
• As an addition to diet and exercise to improve glycemic control in patients with T2D.

The treatment can be initiated in adults with heart failure with an eGFR as low as 20 mL/min/1.73 m2.

More than 650,000 people in the United States are affected by heart failure with high mortality rates, highlighting the need for more treatment options for a broader range of patients. Heart failure is more common with age and is the leading cause of hospitalization in patients over 65 years.

One of the greatest unmet needs in cardiovascular medicine is HFpEF, according to the panel. The risk factors of HFpEf include hypertension, T2D, and chronic obstructive pulmonary disease. Compared to patients with other subtypes of HF, patients with HFpEF have longer average hospital stays and a higher prevalence of comorbidities.

“Recurrent hospitalization is the biggest burden, and cost of care is a big piece of it as well,” Butler said.

Although the life expectancy for patients with HFpEF and HFrEF are very poor, the conditions should be treated as different diseases based on their key features and risk factors, according to Butler. In both the Emperor-Preserved and Emperor-Reserved studies, HFpEF and HFrEF were analyzed and saw statistical significance early on and continued to sustain in each patient as the studies moved forward.

The phase 3 EMPEROR-Preserved trial evaluated the safety and efficacy of empagliflozin as an adjunct to standard of care therapy. Participants administered empagliflozin 10 mg once-daily (n = 2997) were compared with participants administered a placebo (n = 2991). The main efficacy measurements included the time-to-death from cardiovascular causes or need for hospitalization for HF.

Among individuals administered empagliflozin for an average of 2 years, the study found that 14% died from cardiovascular causes or were hospitalized for HF, compared to 17% administered the placebo. The investigators said this benefit was largely attributable to fewer patients being hospitalized for HF

AEs in clinical studies with empagliflozin for patients with HF were consistent with AEs for patients with diabetes. The most common AEs in patients with diabetes were urinary tract infections and female fungal infections.

Butler noted that cardiovascular care continues to evolve, adding that therapies should be administered much sooner to help patients have a better chance of improvement and the continuation to leverage the ability to improve tolerability.

“The ACC ECDP guidelines also mention that there is an urgency that the therapies should be given relatively sooner,” Butler said. “This was not how it used to be given the history of medicine, but this is a new history of medicine.”

REFERENCE

Jardiance (empagliflozin) tablets: A Review of the Latest Data. ACC 2022. April 2, 2022. Accessed April 2, 2022.