title: Clinical efficacy of phosphodiesterase-5 inhibitor tadalafil in Eisenmenger syndrome--a randomized, placebo-controlled, double-blind crossover study.
abstract: OBJECTIVE
  In a randomized double-blind crossover trial, we compared the efficacy of phosphodiesterase-5 (PDE-5) inhibitor tadalafil with placebo in patients of Eisenmenger Syndrome (ES). The primary end point was the change in 6-minute walk test distance (6 MWD). Secondary end points were the effect of the drug on systemic oxygen saturation (SO(2) ), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), effective pulmonary blood flow (EPBF), and World Health Organization (WHO) functional class.
  
  
  BACKGROUND
  ES is a disorder with limited treatment options. Uncontrolled studies have shown PDE-5 inhibitors to be beneficial in patients of ES.
  
  
  METHODS
  Twenty-eight symptomatic adult patients of ES with weight ≥30 kg in WHO class II and III were enrolled. Patients were given 40 mg of tadalafil or matching placebo for 6 weeks followed by crossover to the other drug after a washout period of 2 weeks. Assessment of WHO class, exercise capacity by 6 MWD, and various hemodynamic parameters by cardiac catheterization was done at baseline, after 6 weeks and at the end of the study.
  
  
  RESULTS
  All patients completed the study. There was significant increase in 6 MWD following drug administration compared with baseline (404.18 ± 69.54 m vs. 357.75 ± 73.25 m, P < .001). Compared with placebo, tadalafil produced significant decrease in PVR (-7.32 ± 1.58, P < .001), resulting in significant increase in EPBF (0.12 ± 0.05, P= .03), SO(2) % (1.72 ± 0.58, P= .007), and WHO functional class (1.96 ± 0.18 vs. 2.14 ± 0.44, P= .025), with no significant change in SVR (P= NS).
  
  
  CONCLUSIONS
  In this first short-term placebo-controlled trial of tadalafil in patients of ES, the drug was well tolerated and significantly improved exercise capacity, functional class, SO(2) , and pulmonary hemodynamics.
authors.affiliation: Department of Cardiology, G.B. Pant Hospital, Jawaharlal Nehru Marg, New Delhi, India. saibalmukhopadhyay@yahoo.com
authors.forename: Saibal
authors.initials: S
authors.lastname: Mukhopadhyay
authors.forename: Srikanth
authors.initials: S
authors.lastname: Nathani
authors.forename: Jamal
authors.initials: J
authors.lastname: Yusuf
authors.forename: Devendra
authors.initials: D
authors.lastname: Shrimal
authors.forename: Sanjay
authors.initials: S
authors.lastname: Tyagi
mesh_terms: D000293:Adolescent; D000328:Adult; D002243:Carbolines / Q000009:adverse effects / Q000627:therapeutic use*; D006328:Cardiac Catheterization; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004541:Eisenmenger Complex / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007194:India; D008297:Male; D010100:Oxygen / Q000097:blood; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015990:Placebo Effect; D000068581:Tadalafil; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D014665:Vasodilator Agents; D000068581:Tadalafil; D010100:Oxygen