title: Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathies.
abstract: OBJECTIVE
  During the last decade new approaches to the treatment of pulmonary arterial hypertension (PH) have increased symptomatic relief and prolonged survival. PH is a common sequel of the hemoglobinopathies, thalassemia and sickle cell anemia, but the use of standard oral treatment options, such as calcium channel blockers, endothelin receptor antagonists, and long-term anticoagulation therapy, is limited because of toxicity and poor effectiveness. Sildenafil citrate is a selective and potent inhibitor of cGMP-specific phosphodiesterase-5 (PDE5) which promotes selective smooth muscle relaxation in lung vasculature and has been utilized successfully in the treatment of PH. The primary objective of this study was to evaluate the efficacy of sildenafil treatment in the control of PH in patients with hemoglobinopathies.
  
  
  METHODS
  In this study patients with hemoglobinopathies (thalassemia intermedia n=4; thalassemia major n=2; sickle thalassemia n=1) suffering from severe PH were treated with sildenafil citrate (50 mg b.i.d.) for periods ranging from 4 to 48 months.
  
  
  RESULTS
  A significant decrease in pulmonary pressure and improvement in exercise capacity and functional class were observed in all patients. No significant adverse events were reported.
  
  
  CONCLUSIONS
  These data, in a small group of patients, indicate that sildenafil citrate is effective in the treatment of PH in hemoglobinopathies that cannot be treated with alternative oral drugs and is well tolerated long-term at a daily dose of 100 mg, though studies including more patients may uncover toxicities and limitations of efficacy.
authors.affiliation: Struttura Complessa di Cardiologia, Ospedali Galliera, Genoa, Italy. giorgio.egildo.derchi@galliera.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Derchi
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
authors.forename: Francesco
authors.initials: F
authors.lastname: Formisano
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Giandomenico
authors.initials: G
authors.lastname: D'Ascola
authors.forename: Patrizio
authors.initials: P
authors.lastname: Bina
authors.forename: Carmelo
authors.initials: C
authors.lastname: Magnano
authors.forename: Martina
authors.initials: M
authors.lastname: Lamagna
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001803:Blood Transfusion; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D015150:Echocardiography, Doppler; D005260:Female; D006453:Hemoglobinopathies / Q000150:complications*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011317:Priapism / Q000139:chemically induced / Q000188:drug therapy; D011687:Purines; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate; D013450:Sulfones; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate