Dapagliflozin as a tablet is in clinical development for the treatment of heart failure (HF) with reduced ejection fraction. HF is a complex clinical syndrome of symptoms and signs that suggest the efficiency of the heart as a pump is impaired. Symptoms include breathlessness and fatigue, and signs of the condition include swollen ankles and crackling sounds in the lungs. People with HF often have a poor quality of life, and about a third of people experience severe and prolonged depressive illness. More than half of people with HF have a reduced ejection fraction (HFrEF), also referred to as systolic heart failure, where the heart muscle does not contract effectively, and therefore less oxygen-rich blood is pumped out to the body.
Dapagliflozin blocks the action of a protein in the kidneys called sodium-glucose co-transporter 2 (SGLT2). As blood is filtered by the kidneys, SGLT2 stops glucose in the bloodstream from being passed out into the urine. By blocking the action of SGLT2, dapagliflozin causes the kidney to pass out more glucose in the urine, thereby reducing the levels of glucose in the blood. Blood vessels can be damaged by the effects of high blood glucose levels and this can in turn cause damage to organs, such as the heart. Dapagliflozin may also increase the removal of fluid between tissue cells, contributing to reduced congestion with minimal impact on blood volume. If licensed, dapagliflozin may provide a treatment option for people with HFrEF who currently have limited therapies available.
Icosapent ethyl is in clinical development as a treatment to reduce the risk of cardiovascular events in high-risk patients who have their cholesterol levels controlled with statin treatment, but have elevated triglycerides and other cardiovascular risk factors. Cardiovascular events include heart attack, angina and stroke. These diseases are the main cause of death in the UK, accounting for over a quarter of deaths each year. Patients receiving statin treatment are still at a high risk and would benefit from treatment to reduce cardiovascular events.