title: Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension.
abstract: Pulmonary hypertension is a frequent complication of sickle cell disease that is associated with haemolysis, impaired nitric oxide bioavailability and high mortality. We sought to evaluate the safety and efficacy of selective pulmonary vasodilators and antiproliferative agents in this at-risk population. After optimising sickle cell disease therapy to stabilise haemoglobin and fetal haemoglobin levels, we evaluated the safety and efficacy of sildenafil in 12 patients with sickle cell disease and pulmonary hypertension. Sildenafil therapy (mean duration 6 +/- 1 months) decreased the estimated pulmonary artery systolic pressure [50 +/- 4 to 41 +/- 3 mmHg; difference 9 mmHg, 95% confidence interval (CI): 0.3-17, P = 0.043] and increased the 6-min walk distance (384 +/- 30 to 462 +/- 28 m; difference 78 m, 95% CI: 40-117, P = 0.0012). Transient headaches occurred in two patients and transient eye-lid oedema in four patients. No episodes of priapism occurred in the three men in the study; two of them were on chronic exchange transfusions and one had erectile dysfunction.
  
  
  CONCLUSIONS
  (1) sickle cell disease patients with anaemia and pulmonary hypertension have significant exercise limitation; (2) the 6-min walk distance may be a valid endpoint in this population; (3) therapy with sildenafil appears safe and improves pulmonary hypertension and exercise capacity. Additional phase I studies in males with sickle cell disease followed by phase II/III placebo controlled trials evaluating the safety and efficacy of sildenafil therapy in sickle cell disease patients with pulmonary hypertension are warranted.
authors.affiliation: Vascular Therapeutics Section, Cardiovascular Branch, National Heart Lung and Blood Institute, Bethesda, MD, USA. robertom@nhlbi.nih.gov
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
authors.forename: Sabrina
authors.initials: S
authors.lastname: Martyr
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kato
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.forename: Anastasia
authors.initials: A
authors.lastname: Anthi
authors.forename: Michael R
authors.initials: MR
authors.lastname: Robinson
authors.forename: Lori
authors.initials: L
authors.lastname: Hunter
authors.forename: Wynona
authors.initials: W
authors.lastname: Coles
authors.forename: James
authors.initials: J
authors.lastname: Nichols
authors.forename: Christian
authors.initials: C
authors.lastname: Hunter
authors.forename: Vandana
authors.initials: V
authors.lastname: Sachdev
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Castro
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D006328:Cardiac Catheterization; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines; D015203:Reproducibility of Results; D000068677:Sildenafil Citrate; D018709:Statistics, Nonparametric; D013450:Sulfones; D013599:Systole; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate