Anastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial.
The aromatase inhibitor anastrozole blocks the conversion of androgens to estrogen and blunts pulmonary hypertension in animals, but its efficacy in treating patients with pulmonary arterial hypertension (PAH) is unknown.



We aimed to determine the safety and efficacy of anastrozole in PAH.



We performed a randomized, double-blind, placebo-controlled trial of anastrozole in patients with PAH who received background therapy at two centers.



A total of 18 patients with PAH were randomized to anastrozole 1 mg or matching placebo in a 2:1 ratio. The two co-primary outcomes were percent change from baseline in 17β-estradiol levels (E2) and tricuspid annular plane systolic excursion (TAPSE) at 3 months. Anastrozole significantly reduced E2 levels compared with placebo (percent change: -40%; interquartile range [IQR], -61 to -26% vs. -4%; IQR, -14 to +4%; P = 0.003), but there was no difference in TAPSE. Anastrozole significantly increased the 6-minute-walk distance (median change = +26 m) compared with placebo (median change = -12 m) (median percent change: anastrozole group, 8%; IQR, 2 to 17% vs. placebo -2%; IQR, -7 to +1%; P = 0.042). Anastrozole had no effect on circulating biomarkers, functional class, or health-related quality of life. There was no difference in adverse events.



Anastrozole significantly reduced E2 levels in patients with PAH but had no effect on TAPSE. Anastrozole was safe, well tolerated, and improved 6-minute-walk distance in this small "proof-of-principle" study. Larger and longer phase II clinical trials of anastrozole may be warranted in patients with PAH. Clinical trial registered with www.clinicaltrials.gov (NCT 1545336).
1 Department of Medicine and.|2 Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Steven M
SM
Kawut
1 Department of Medicine and.
Christine L
CL
Archer-Chicko
1 Department of Medicine and.
Angela
A
DeMichele
1 Department of Medicine and.
Jason S
JS
Fritz
3 Rhode Island Hospital, Providence, Rhode Island.|4 Department of Medicine, and.
James R
JR
Klinger
1 Department of Medicine and.
Bonnie
B
Ky
1 Department of Medicine and.
Harold I
HI
Palevsky
3 Rhode Island Hospital, Providence, Rhode Island.
Amy J
AJ
Palmisciano
1 Department of Medicine and.
Mamta
M
Patel
1 Department of Medicine and.
Diane
D
Pinder
2 Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Kathleen J
KJ
Propert
1 Department of Medicine and.
K Akaya
KA
Smith
5 Department of Obstetrics and Gynecology, Keck School of Medicine of the University of Southern California, Los Angeles, California; and.
Frank
F
Stanczyk
6 Department of Laboratory Medicine, University of Vermont School of Medicine, Burlington, Vermont.
Russell
R
Tracy
1 Department of Medicine and.
Anjali
A
Vaidya
3 Rhode Island Hospital, Providence, Rhode Island.|4 Department of Medicine, and.
Mary E
ME
Whittenhall
3 Rhode Island Hospital, Providence, Rhode Island.|4 Department of Medicine, and.|7 Department of Health Services, Policy and Practice, Brown University, Providence, Rhode Island.
Corey E
0000-0002-4223-4775
CE
Ventetuolo
D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011374:Progesterone / Q000097:blood; D013256:Steroids / Q000097:blood*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D015415:Biomarkers; D012739:Gonadal Steroid Hormones; D009570:Nitriles; D013256:Steroids; D014230:Triazoles; D004970:Estrone; D000077384:Anastrozole; D011374:Progesterone; D004958:Estradiol
anastrozole; clinical trial; pulmonary hypertension; sex hormones