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A New Frontier in Aortic Valve Stenosis Treatment: Ataciguat

Aortic valve stenosis (AVS) is a serious medical issue impacting more than 1.5 million individuals in the United States and millions around the world. Research conducted at the Mayo Clinic is investigating the efficacy of a novel drug, ataciguat, as a treatment option for this condition. Findings from both preclinical and clinical investigations, published in the journal Circulation, indicate that ataciguat may have the capability to significantly decelerate the progression of AVS. To validate the drug’s long-term efficacy and safety, a phase 3 trial is set to commence soon in collaboration with an industry partner.

AVS arises when calcium buildup narrows the aortic valve, compelling the heart to exert greater effort to circulate blood. This ailment typically worsens over time, manifesting symptoms such as chest pain, breathlessness, and fatigue, particularly in individuals aged 65 and older. The conventional approach to managing AVS—watchful waiting—often results in a diminished quality of life before surgical intervention becomes necessary.

Dr. Jordan Miller, who leads the Cardiovascular Disease and Aging Laboratory at the Mayo Clinic, emphasized the significance of this research, stating, “This work represents a major leap forward in the treatment landscape for aortic valve stenosis. Ataciguat has the potential to significantly postpone or even eliminate the need for valve replacement surgery, enhancing the quality of life for countless patients.”

Furthermore, Dr. Miller pointed out that the implications of this treatment extend beyond just delaying surgical intervention. Patients who are younger and diagnosed with aggressive AVS or congenital valve abnormalities may start experiencing symptoms earlier in life. If valve replacement becomes necessary before the age of 55, there is a heightened risk—over 50%—that these patients will require multiple heart surgeries subsequently due to the calcification of the replacement valve. Ataciguat, which has shown promise in slowing the calcification process in clinical settings, could enable patients to undergo a single valve replacement procedure and reach a much older age before any complications arise, thereby optimizing their outcomes.

Research over the past ten years at the Mayo Clinic has revealed that ataciguat can rejuvenate a pathway integral to preventing both valvular calcification and stenosis. Experiments conducted on mice demonstrated that initiating treatment with ataciguat after the onset of the disease effectively slowed its progression.

In human clinical trials involving patients with moderate AVS, a once-daily regimen of ataciguat was well received, resulting in minimal side effects relative to a placebo. In a recent phase 2 study that included 23 participants, ataciguat yielded a remarkable 69.8% reduction in the progression of aortic valve calcification after six months, with treated patients also exhibiting better heart muscle function. Importantly, the study found that ataciguat had no adverse effects on bone formation, despite its significant influence on calcification rates.

This pivotal research has emerged from a robust collaboration involving the Mayo Clinic, the National Institutes of Health, the University of Minnesota, and Sanofi Pharmaceuticals. It has been facilitated by innovative partnerships and funding from the National Center for Accelerating Translational Sciences, along with a grant from the Minnesota Biotechnology and Genomics Partnership.

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