A newly released study found that people with heart failure who received the diabetes drug empagliflozin showed significant improvements in heart structure and function, with many experiencing a reversal of the disease.
Approximately 6.2 million adults in the United States have heart failure. As a result of its high prevalence, the national cost of healthcare services, medicines, and missed workdays related to this disorder reached an estimated $30.7 billion in 2012.
Globally, the disease affects approximately 23 million people.
Heart failure occurs when the heart cannot pump blood effectively to other parts of the body, causing symptoms that include shortness of breath, difficulty breathing, weakness and tiredness, and weight gain and swelling in the legs, ankles, feet, or stomach.
It may progress to congestive heart failure due to the buildup of fluids in the lungs, liver, and lower extremities.
Underlying causes of heart failure include coronary artery disease, high blood pressure, obesity, heart valve disease, and diabetes. Over time, these diseases may result in “adverse modeling,” which is the heart’s attempt to compensate for its added workload by getting larger, developing thicker walls, and pumping more frequently.
Among people with heart failure, about 50% present with heart failure with reduced ejection fraction (HFrEF). The lowered ejection fraction occurs when the heart’s left ventricle cannot pump blood effectively, decreasing the amount of blood that leaves the ventricle to circulate the body after each contraction.
Treatment options for heart failure include taking prescription drugs, reducing the amount of sodium in the diet, consuming a lower volume of liquids, and making any necessary lifestyle changes, such as reaching a moderate weight, quitting smoking, and eating a heart-healthy diet.
With limited heart failure treatment options available, researchers from the Icahn School of Medicine at Mount Sinai set up a clinical trial called EMPATROPISM to investigate the use of empagliflozin, a diabetes drug, for treating HFrEF in people without diabetes.
The researchers presented the trial results on November 13 at the American Heart Association (AHA) Scientific Sessions 2020, with a pre-proof appearing in the Journal of the American College of Cardiology.
In the double-blind, placebo-controlled, randomized study, the scientists divided the 84 participants, who were 18–85 years of age, into two groups. One group received 10 milligrams (mg) of empagliflozin daily, and the other took a placebo.
At the trial’s onset, all of the participants underwent baseline evaluations, which included cardiac MRI, a 6-minute walk test, and a cardiopulmonary exercise test to determine their oxygen levels. They also completed questionnaires regarding their quality of life.
After 6 months of receiving either the placebo or empagliflozin, the participants completed the same tests again.
The researchers found that approximately 80% of those who received the medication showed significant improvement in their condition, with a 16.6% improvement in left ventricle ejection fraction.
They also experienced a reduction in heart size and thickness and had less congestion, indicating that their heart failure had become less severe.
Remarkably, the investigators note that the heart returned to near normal in this group of participants.
Additionally, those who received empagliflozin experienced no severe side effects and saw improvements in their exercise levels and quality of life, which occurred relatively quickly after beginning the medication.
Although empagliflozin is an antidiabetes drug, the investigators noted no adverse blood sugar-related side effects, such as hypoglycemia, in the study participants, despite them not having diabetes.
Conversely, the study participants who took the placebo showed no improvements. Their condition either stayed the same or worsened, with a further reduced ejection fraction, increased heart size and thickness, and an abnormal change in the heart’s overall shape.
According to the researchers, the study results also explain why this medication effectively treats heart failure. They explain that it essentially reverses the adverse modeling that occurs when the heart attempts to restructure itself to compensate for changes associated with other chronic conditions.
The EMPEROR-Reduced trial, a slightly earlier study that featured in the New England Journal of Medicine, saw similar results. In this double-blind trial, 3,730 people with HFrEF took either empagliflozin (10 mg once daily) or a placebo, in addition to recommended therapy.
The results concurred with the EMPATROPISM findings, showing that people both with and without diabetes in the empagliflozin group experienced a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group.
The EMPATROPISM study’s first author, Carlos Santos-Gallego, a postdoctoral fellow at the Icahn School of Medicine, explains the implications of these findings.
He says, “Our clinical trial’s promising results show this diabetes drug can ameliorate lives of heart failure patients with reduced ejection fraction, enhance their exercise capacity, and improve their quality of life with little to no side effects.”
“We expect this work will help lead to U.S. Food and Drug Administration [FDA] approval of empagliflozin for this patient population in the coming months.”