Active ingredient from red foxglove helps with heart failure, clinical study confirms

Digitalis has been used to treat heart failure for more than 200 years. The drug digitoxin also belongs to this group of active ingredients known as cardiac glycosides.

Although there were indications that digitalis was beneficial in heart failure, it has only now been scientifically proven that digitoxin has a significant positive effect in heart failure due to reduced pumping function and insufficient emptying of the left ventricle—known in medical terms as HFrEF (heart failure with reduced ejection fraction).

For 10 years, researchers led by Professor Dr. Johann Bauersachs, Director of the Department of Cardiology and Angiology at Hanover Medical School (MHH), and senior physician Professor Dr. Udo Bavendiek thoroughly investigated the safety and efficacy of the active ingredient in a clinical study involving more than 1,200 participants.

The large-scale DIGIT-HF study coordinated by them, involving more than 50 centers in Germany, Austria and Serbia, has now been completed and delivers a clear result: adjunctive therapy with digitoxin reduces mortality and the number of hospitalizations for heart failure in patients with advanced HFrEF.

The results have been published in the New England Journal of Medicine. At the same time, they were presented at the end at the European Society of Cardiology Congress in Madrid in the so-called Hot Line Session, where new clinical studies that promise significant changes in patient outcomes are presented.

No proof of effectiveness according to scientific standards to date

Our heart is a high-performance engine. It beats around 70 times per minute, pumping around five liters of blood through our vessels. In doing so, it supplies the body with vital oxygen and nutrients. If this pumping capacity is permanently reduced, doctors refer to this as chronic heart failure or cardiac insufficiency.

Around four million people in Germany are affected. Symptoms include shortness of breath, low exercise tolerance, water retention, immobility and severe arrhythmia. The condition is one of the most common reasons for hospitalization and even death. Until around 2020, digitalis preparations were still on the production list of major pharmaceutical companies.

Currently, digitoxin is only produced as a generic drug. “However, it remains the most commonly used digitalis preparation in Germany—so far, however, without any scientifically proven evidence of its effectiveness,” notes Professor Bavendiek.

Can also be used in cases of impaired kidney function

This has now been proven. “In the DIGIT-HF study, we examined patients who had exhausted all conventional treatment options,” says Professor Bauersachs. “We were surprised ourselves that we were able to achieve such a significant improvement with the additional digitoxin treatment in these very well-treated study participants.”

The usual medications for heart failure include beta blockers and inhibitors of the renin-angiotensin-aldosterone system, which inhibit excessively activated hormone cascades and thus relieve the heart, as well as diuretics. Defibrillators, which are implanted in the patient’s body, also help against acute arrhythmias.

Since 2021, so-called SGLT-2 inhibitors have also been used in Germany. These were originally approved for the treatment of type 2 diabetes, but also have positive effects in all forms of heart failure. Thanks to the DIGIT-HF study, digitoxin could now become another mainstay in the treatment of people diagnosed with HFrEF.

Previous clinical studies have been conducted almost exclusively with digoxin, another cardiac glycoside. However, digoxin can only be used to a limited extent in patients with impaired kidney function, which is often the case in patients with advanced heart failure, as it is excreted almost exclusively via the kidneys.

“With digitoxin, however, the situation is different,” explains Professor Bavendiek. This is because digitoxin is excreted via the liver and intestines to a greater extent in patients with impaired kidney function. The already-approved drug is therefore also suitable for use in patients with pre-existing kidney weakness.

Safe and cost-effective

In addition, the results of the DIGIT-HF study dispelled fears that digitoxin is dangerous for certain groups of patients with heart failure and could lead to death.

“When dosed correctly, digitoxin is a safe treatment for heart failure and is also suitable for controlling heart rate in atrial fibrillation when beta blockers alone are not sufficient,” emphasizes Professor Bavendiek.

Another advantage of the drug sounds trivial, but is certainly interesting in view of rising health care costs: digitoxin costs just a few cents and is drastically cheaper than other drugs for heart failure. Based on the study data available to date, heart specialists have already developed recommendations for simple and safe dosing.

Whereas 0.1 milligrams of digitoxin were often prescribed in the past, the current recommendations are 0.07 milligrams per day or even less. The DIGIT-HF study showed that this dosage reduced mortality and hospital admissions due to heart failure without any safety issues.