Aortic valve stenosis (AVS) affects over 1.5 million Americans and many more worldwide, posing a significant health challenge. Researchers at Mayo Clinic are investigating ataciguat, a new drug that could potentially manage AVS by slowing its progression. Published findings in Circulation from preclinical and clinical studies suggest ataciguat's promising role in delaying disease advancement. A phase 3 trial is being planned with an industry partner to confirm the drug's long-term safety and effectiveness.
AVS occurs when calcium deposits narrow the aortic valve, making it harder for the heart to pump blood. This condition often worsens over time, causing symptoms such as chest pain, shortness of breath, and fatigue in people over 65 years old. The current treatment approach involves watchful waiting until surgery becomes necessary.
"This research represents a significant advancement in the treatment of aortic valve stenosis," said Jordan Miller, Ph.D., director of the Cardiovascular Disease and Aging Laboratory at Mayo Clinic. "Ataciguat has the potential to substantially delay or even prevent the need for valve replacement surgery, significantly improving the lives of millions."
Dr. Miller emphasized that younger patients with aggressive forms of AVS or congenital defects might benefit significantly from ataciguat if they require surgery before age 55. Currently, these patients face a high likelihood of needing multiple surgeries due to recalcification. Ataciguat showed promise in clinical trials by slowing native aortic valve calcification progression, which may lead to fewer surgeries if patients can reach age 65.
Research conducted over ten years at Mayo Clinic revealed that ataciguat reactivates pathways preventing valvular calcification and stenosis. Preclinical mouse studies indicated significant slowing of disease progression even when treatment began after disease onset.
In human trials involving patients with moderate AVS, once-daily dosing of ataciguat was well tolerated with minimal side effects compared to placebo. A recent phase 2 trial involving 23 patients demonstrated a notable reduction in calcification progression by nearly 70% at six months compared to placebo, while maintaining better heart muscle function without affecting bone formation.
The research results from collaboration between Mayo Clinic, National Institutes of Health, University of Minnesota, and Sanofi Pharmaceuticals under academic-industry partnership grants administered by national centers.
Mayo Clinic and Dr. Miller hold financial interests related to this research but will use any revenue generated to support their nonprofit mission focused on patient care, education, and research initiatives.
