Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension

Haematologica. 2013 Sep;98(9):1359-67. doi: 10.3324/haematol.2012.082065. Epub 2013 Apr 12.


Pulmonary hypertension is a common but often overlooked complication associated with thalassemia syndromes. There are limited data on the safety and efficacy of selective pulmonary vasodilators in this at-risk population. We, therefore, designed a 12-week, open-label, phase 1/2, pilot-scale, proof-of-principle trial of sildenafil therapy in 10 patients with β-thalassemia and at increased risk of pulmonary hypertension based on an elevated tricuspid regurgitant jet velocity >2.5 m/s on Doppler-echocardiography. Variables compared at baseline and after 12 weeks of sildenafil treatment included Doppler-echocardiographic parameters, 6-minute walked distance, Borg Dyspnea Score, New York Heart Association functional class, pulmonary function, and laboratory parameters. Treatment with sildenafil resulted in a significant decrease in tricuspid regurgitant jet velocity by 13.3% (3.0±0.7 versus 2.6±0.5 m/s, P=0.04), improved left ventricular end systolic/diastolic volume, and a trend towards a improved New York Heart Association functional class. No significant change in 6-minute walked distance was noted. Sildenafil was well tolerated, although minor expected adverse events were commonly reported. The total dose of sildenafil (mg) was strongly correlated with percent change in nitric oxide metabolite concentration in the plasma (ρ=0.80, P=0.01). There were also significant increases in plasma and erythrocyte arginine concentrations. Our study suggests that sildenafil is safe and may improve pulmonary hemodynamics in patients at risk of pulmonary hypertension; however, it was not demonstrated to improve the distance walked in 6 minutes. Clinical trials are needed to identify the best treatment strategy for pulmonary hypertension in patients with β-thalassemia. ( identifier: NCT00872170).

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Echocardiography, Doppler / methods
  • Female
  • Humans
  • Hypertension, Pulmonary / diagnostic imaging*
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / epidemiology
  • Male
  • Middle Aged
  • Pilot Projects
  • Piperazines / therapeutic use*
  • Purines / therapeutic use
  • Risk Factors
  • Sildenafil Citrate
  • Sulfones / therapeutic use*
  • Thalassemia / diagnostic imaging*
  • Thalassemia / drug therapy*
  • Thalassemia / epidemiology
  • Vasodilator Agents / therapeutic use*


  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sildenafil Citrate

Associated data