Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension
Claudia R Morris, Hae-Young Kim, John Wood, John B Porter, Elizabeth S Klings, Felicia L Trachtenberg, Nancy Sweeters, Nancy F Olivieri, Janet L Kwiatkowski, Lisa Virzi, Sylvia T Singer, Ali Taher, Ellis J Neufeld, Alexis A Thompson, Vandana Sachdev, Sandra Larkin, Jung H Suh, Frans A Kuypers, Elliott P Vichinsky, Thalassemia Clinical Research Network, Ellis Neufeld, Jennifer Eile, Latoya Lashley, Charles Quinn, Deborah Boger, Leah Adix, Brad Cook, Patricia Giardina, Dorothy Kleinert, Janet Kwiatkowski, Sage Green, Alexis Thompson, Janice Beatty, Diane Calamaras, Pauline Hess, Claudia Morris, Elliott Vichinsky, Nancy Sweeters, Nancy F Olivieri, Renata Dzackova, Cecilia Kim, Vivek Thayalasuthan, John Porter, Cindy Bhagwandin, Ali Taher, Tannous Fakhry, Kathryn Hassell, Sonja McKinlay, Lisa Virzi, Felicia Trachtenberg, Claudia R Morris, Hae-Young Kim, John Wood, John B Porter, Elizabeth S Klings, Felicia L Trachtenberg, Nancy Sweeters, Nancy F Olivieri, Janet L Kwiatkowski, Lisa Virzi, Sylvia T Singer, Ali Taher, Ellis J Neufeld, Alexis A Thompson, Vandana Sachdev, Sandra Larkin, Jung H Suh, Frans A Kuypers, Elliott P Vichinsky, Thalassemia Clinical Research Network, Ellis Neufeld, Jennifer Eile, Latoya Lashley, Charles Quinn, Deborah Boger, Leah Adix, Brad Cook, Patricia Giardina, Dorothy Kleinert, Janet Kwiatkowski, Sage Green, Alexis Thompson, Janice Beatty, Diane Calamaras, Pauline Hess, Claudia Morris, Elliott Vichinsky, Nancy Sweeters, Nancy F Olivieri, Renata Dzackova, Cecilia Kim, Vivek Thayalasuthan, John Porter, Cindy Bhagwandin, Ali Taher, Tannous Fakhry, Kathryn Hassell, Sonja McKinlay, Lisa Virzi, Felicia Trachtenberg
Abstract
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. (clinicaltrials.gov identifier: NCT00872170).
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Source: PubMed