title: Sex differences in response to tadalafil in pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a progressive disease with high rates of morbidity and mortality. Current therapies improve symptoms, functional capacity, and, in select cases, survival. Little is known about patient factors that may predict the likelihood of patient-important, clinically relevant responses to therapy such as the 6-min walk distance (6MWD) and health-related quality of life (HRQoL).
  
  
  METHODS
  Data from the randomized clinical trial of tadalafil in PAH were used. Adjusted logistic regression models were created to examine the relationship between baseline characteristics and odds of achieving the minimal important difference (MID) in three parameters, defined as either a > 33-m increase in 6MWD, a > 5-unit increase in physical component summary score of the Medical Outcomes Study Short Form-36 (SF-36), or a > 5-unit increase in mental component summary score of the SF-36.
  
  
  RESULTS
  The study included 405 subjects. Younger age, male sex, lower baseline 6MWD, and disease etiology were associated with greater odds of achieving the MID for the 6-min walk test. Active treatment, younger age, and male sex were associated with greater odds of achieving the MID for the physical component summary score. Male sex was associated with greater odds of achieving the MID for the mental component summary score.
  
  
  CONCLUSIONS
  Age, sex, baseline functional capacity, and disease etiology are variably associated with the likelihood of achieving clinically relevant responses in patient-important outcomes to PAH-specific therapy such as 6MWD and HRQoL. The increased likelihood of response in men compared with women is a novel finding and may reflect pathophysiologic differences between sexes.
authors.affiliation: Division of Pulmonary and Critical Care Medicine (Drs Mathai, Hassoun, and Wise), Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Mathai
authors.affiliation: Division of Pulmonary and Critical Care Medicine (Drs Mathai, Hassoun, and Wise), Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: smathai4@jhmi.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hassoun
authors.affiliation: Division of Pulmonary and Critical Care Medicine (Drs Mathai, Hassoun, and Wise), Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Milo A
authors.initials: MA
authors.lastname: Puhan
authors.affiliation: United Therapeutics Corporation, Research Triangle Park, NC.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland; and United Therapeutics Corporation, Research Triangle Park, NC.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wise
mesh_terms: D000959:Antihypertensive Agents; D002243:Carbolines / Q000008:administration & dosage*; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D015995:Prevalence; D011669:Pulmonary Wedge Pressure / Q000187:drug effects*; D011788:Quality of Life; D017678:Sex Distribution; D012737:Sex Factors; D000068581:Tadalafil; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D000959:Antihypertensive Agents; D002243:Carbolines; D014665:Vasodilator Agents; D000068581:Tadalafil