• Steven M Kawut, Rui Feng, Susan S Ellenberg, Roham Zamanian, Todd Bull, Murali Chakinala, Stephen C Mathai, Anna Hemnes, Grace Lin, Margaret Doyle, Ruth Andrew, Margaret MacLean, Ioannis Stasinopoulos, Eric Austin, Angela DeMichele, Haochang Shou, Jasleen Minhas, Nianfu Song, Jude Moutchia, and Corey E Ventetuolo.
• University of Pennsylvania Perelman School of Medicine, 14640, Medicine , Philadelphia, Pennsylvania, United States; kawut@upenn.edu.
• Am. J. Respir. Crit. Care Med. 2024 May 15.

RationaleInhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models.ObjectivesWe aimed to determine whether anastrozole improved six-minute walk distance (6MWD) at six months in pulmonary arterial hypertension (PAH).MethodsWe performed a randomized, double-blind, placebo-controlled Phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four post-menopausal women and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at six months. Using intent-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters.Measurements And Main ResultsForty-one subjects were randomized to placebo and 43 to anastrozole and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued study drug. There was no significant difference in the change in 6MWD at six months (placebo-corrected treatment effect -7.9 m, 95%CI -32.7 - 16.9, p = 0.53). There was no difference in adverse events between the groups.ConclusionsAnastrozole did not show a significant effect on 6MWD compared to placebo in post-menopausal women and men with PAH. Anastrozole was safe and did not show adverse effects. Clinical trial registration available at www.Clinicaltrialsgov, ID: NCT03229499.

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