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Among female patients with aortic stenosis, angiotensin II receptor blockers (ARBs) may help reduce fibrosis of the aortic valve. 

A retrospective study aimed to determine whether a sex-specific difference exists in the relationship between ARBs and the progression of disease in patients with aortic stenosis. The study included data from 1321 patients who had received aortic valve replacement with or without coronary bypass grafting. It found that among female patients, who tended to have more fibrosis than their male counterparts, those taking ARBs had lower fibrosis scores. 

"Right now, we don't have any medication to slow the progression of aortic stenosis," study author Rasmus Carter-Storch, MD, PhD, a cardiologist at Odense University Hospital in Denmark and Université Laval in Québec, Canada, told Medscape Medical News. The findings indicate that angiotensin blockers could serve that role, particularly for female patients.

The study was published on March 20, 2024, in the Canadian Journal of Cardiology.

Slowing Disease Progression

Aortic stenosis is the most common valvular disease in high-income countries. As the disease progresses, fibrosis and calcification in the aorta build, and it becomes difficult for the valve to open properly. The disease is often accompanied by hypertension, which can be treated by ARBs, an inexpensive and well-tolerated medication. 

Under the current standard of care, cardiologists treat aortic stenosis by waiting until the disease progresses enough to require surgical replacement of the value. If a drug could help slow the progression of the disease, it would delay the invasive treatment and improve care, said Carter-Storch. Other medications used to lower cholesterol, such as statins, have failed to slow the disease in previous research, he added.

The study drew data from a large database of patients with severe aortic stenosis who had an aortic valve replacement between 2006 and 2013 at a hospital in Quebec. The 1321 patients included were divided into the following four groups, based on the severity of disease: Mild fibrosis and calcification, predominant fibrosis, predominant calcification, and severe fibrosis and calcification. 

The investigators found that female patients were more likely to belong to the predominant fibrosis group (odds ratio, 1.45), which supported previous findings. But in those female patients, participants taking ARBs had significantly lower fibrosis scores. Meanwhile, the difference was not observed in male patients, suggesting that the effects of ARBs may be sex-specific. 

Promising but Preliminary

Because of the study design, which drew from patients whose disease had progressed to the point of requiring surgery, most patients had severe aortic stenosis (89%). The remaining patients' disease progression was moderate.

Thus, because the study was retrospective and included many patients with severe aortic stenosis, Carter-Storch noted that it is not clear if the medication itself caused the reduced fibrosis. He added that cardiologists should refrain from making clinical recommendations until randomized controlled trials are completed. "This is preliminary, but it's a promising finding." The same research group is conducting a large, ongoing randomized controlled trial to determine the clinical effects of ARBs on disease progression. 

For the future, the investigators recommend additional randomized clinical trials to better assess the sex-specific association, beginning with patients who have mild to moderate aortic stenosis. Other retrospective studies could gather important data on how the duration of ARB use affects disease progression. 

Well-Performed Study

Commenting on the study for Medscape Medical News, Roopinder Sandhu, MD, MPH, director of the Women's Cardiovascular Health Initiative at the University of Calgary's Libin Cardiovascular Institute, Alberta, Canada, said that it is important, well performed, and has a clear rationale, given that previous evidence suggests that ARBs may have an antifibrotic effect. With the current lack of proven medical therapies to slow the progression of aortic stenosis, "there's a gap in terms of our management options," said Sandhu. 

In addition, women are underrepresented in cardiovascular disease research as a whole, according to Sandhu. "Cardiovascular disease in women remains understudied, underrecognized, underdiagnosed, and undertreated." More studies are needed to improve our understanding of sex differences in the manifestation and treatment of heart disease, she said. 

Sandhu believes it is too early to apply the findings in clinical practice because of the limitations inherent in observational studies. For example, it is unclear how the 810 patients in the database who were excluded from the study may compare with the study cohort. She also noted that the investigators were unable to examine dose effects or whether the duration of ARB use plays a role, which could provide areas of future research. 

The study was conducted without outside funding. Carter-Storch reported receiving travel grants from Astra Zeneca and Abbott outside the submitted work. Sandhu reported no relevant financial relationships.

Gwendolyn Rak is a health reporter for Medscape based in Brooklyn, New York.