Istaroxime is an investigational drug, administered intravenously, being developed for acute heart failure. It aims to improve both heart contraction and relaxation. Its unique properties are being investigated for managing heart function.
How Istaroxime Works
Istaroxime operates through a dual mechanism. It inhibits the sodium-potassium adenosine triphosphatase (Na+/K+ ATPase) pump while simultaneously stimulating the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) calcium pump.
The inhibition of Na+/K+ ATPase leads to an increase in intracellular sodium levels. This indirectly enhances calcium entry, necessary for muscle contraction. The simultaneous activation of SERCA2a accelerates the reuptake of calcium into the sarcoplasmic reticulum, a specialized storage compartment within muscle cells. This dual action results in a stronger heart muscle contraction (inotropy) and improved relaxation (lusitropy), allowing the heart to fill more efficiently. This improved calcium handling is particularly relevant as abnormal calcium regulation is a feature of heart failure.
Its Role in Acute Heart Failure
Acute heart failure (AHF) is a condition where the heart cannot pump enough blood to meet the body’s needs, leading to symptoms like shortness of breath and fluid buildup. This condition is a frequent cause of hospitalization and is associated with health risks. The heart’s inability to pump effectively results from compromised contractility and impaired relaxation.
Istaroxime’s dual mechanism addresses these issues by strengthening heart pumping and improving its ability to relax and fill. By increasing myocardial contractility, istaroxime helps the heart eject more blood with each beat. The improved relaxation allows the heart chambers to properly fill, important for effective pumping. This improvement in cardiac function can alleviate symptoms and underlying problems for patients with acute heart failure.
Distinct Advantages and Safety Profile
Existing treatments for acute heart failure, particularly other inotropic agents, can lead to side effects. These include increased heart rate or abnormal heart rhythms (arrhythmias). These side effects can complicate patient management and worsen outcomes.
Istaroxime distinguishes itself by increasing systolic blood pressure without accelerating heart rate or causing arrhythmias. This safety profile is an advantage, suggesting istaroxime might improve cardiac function with a lower risk of these adverse effects. Its ability to enhance both contraction and relaxation while maintaining a stable heart rhythm makes it a promising option compared to current therapies.
Current Research and Future Outlook
Istaroxime is currently undergoing clinical trials to evaluate its safety and effectiveness. It has completed multiple Phase 2 studies, with positive results reported for patients with acute heart failure and early cardiogenic shock. These studies have shown that istaroxime can improve cardiac function and blood pressure.
Research, including a Phase 2b extension study focusing on dose optimization and SERCA2a effects, is underway. The drug has received Fast Track designation from the U.S. Food and Drug Administration (FDA), highlighting the unmet medical need for acute heart failure treatments. While initial findings are encouraging, larger Phase 3 trials are necessary to understand its long-term effects and compare its performance against established treatments before wide availability.