Conference Coverage

Ataciguat Slows Aortic Valve Calcification and Preserves Cardiac Function in Patients with Moderate Aortic Stenosis

Anthony Calabro, MA

Key Highlights

  • Ataciguat reduced progression of aortic valve calcification compared with placebo.
  • Reduced calcification correlated with preserved aortic valve area and cardiac output.
  • Patients receiving ataciguat showed improvements in systolic function.
  • Findings support larger clinical trials to confirm cardiac and valvular benefits.

Introduction

New findings presented by investigators from Vanderbilt University Medical Center and collaborating centers at the American Heart Association Scientific Sessions 2025 highlight ataciguat, a soluble guanylate cyclase activator, as a potential medication to modify the course of moderate calcific aortic valve stenosis (CAVS).

The phase 2 study examined whether slowing the accumulation of aortic valvular calcium (AVC) with ataciguat could preserve cardiac performance. The results suggest that targeting the underlying calcific process may improve both valvular mechanics and ventricular function.

Methods

This double-blind, randomized, phase 2 trial enrolled 23 patients with moderate CAVS, who were assigned 1:1 to ataciguat 200 mg daily or placebo for up to 12 months. The primary endpoint was change in AVC measured by cardiac CT. Secondary assessments included aortic valve area (AVA), cardiac output (CO), and measures of left ventricular structure and function. AVA was determined using the Modified Gorlin (Hakki) equation to evaluate valvular compliance. Correlations between AVC, AVA, and cardiac measures were analyzed using exploratory linear mixed models.

Study Findings

In patients receiving ataciguat, changes in AVC were inversely correlated with AVA (slope = −0.0002; 95% CI, −0.0004 to 0.0001), indicating that reduced calcium deposition was associated with preserved valve area. Improvements in AVA were directly correlated with higher CO (slope = 0.16; 95% CI, 0.13–0.18). Compared with placebo, ataciguat treatment was linked to better systolic function and less progression of calcification. Changes in AVC also correlated inversely with CO (slope = −0.0007; 95% CI, −0.0021 to 0.0008), suggesting that patients with slower AVC progression experienced improved hemodynamic function.

Clinical Implications

These findings highlight the therapeutic potential of ataciguat to slow disease progression in moderate CAVS, a condition for which valve replacement remains the only effective treatment. By reducing calcification and maintaining valvular compliance, ataciguat may help preserve cardiac output and delay the onset of heart failure. This approach could represent a paradigm shift toward early, medical intervention in CAVS management.

Expert Commentary

The investigators noted that “slowing the rate of AVC deposition with [ataciguat] may result in improvements in CO through improved myocardial function and valvular compliance.” The investigators also noted that larger, controlled studies are warranted to confirm these results and determine whether improved hemodynamics translate into better long-term outcomes.

Conclusion

The phase 2 trial results indicate that ataciguat may attenuate aortic valve calcification and preserve cardiac function in patients with moderate aortic stenosis. By improving myocardial and valvular performance, ataciguat offers promise as a novel medical therapy targeting the pathophysiology of CAVS. Further studies will be essential to validate these findings and assess clinical benefit.

Reference
Michelena HI, Pibarot P, Moore L, et al. Impact of aortic valve calcification on functional valve area and cardiac structure and function in a phase 2 trial of ataciguat. Presented at: American Heart Association Scientific Sessions 2025; New Orleans, LA. https://professional.heart.org/en/meetings/scientific-sessions