title: Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity.
abstract: In adults with sickle cell disease (SCD), an increased tricuspid regurgitation velocity (TRV) by Doppler echocardiography is associated with increased morbidity and mortality. Although sildenafil has been shown to improve exercise capacity in patients with pulmonary arterial hypertension, it has not been evaluated in SCD. We therefore sought to determine whether sildenafil could improve exercise capacity in SCD patients with increased TRV and a low exercise capacity. A TRV ≥ 2.7 m/s and a 6-minute walk distance (6MWD) between 150 and 500 m were required for enrollment in this 16-week, double-blind, placebo-controlled sildenafil trial. After 74 of the screened subjects were randomized, the study was stopped early due to a higher percentage of subjects experiencing serious adverse events in the sildenafil arm (45% of sildenafil, 22% of placebo, P = .022). Subject hospitalization for pain was the predominant cause for this difference: 35% with sildenafil compared with 14% with placebo (P = .029). There was no evidence of a treatment effect on 6MWD (placebo-corrected effect -9 m; 95% confidence interval [95% CI] -56-38; P = .703), TRV (P = .503), or N-terminal pro-brain natriuretic peptide (P = .410). Sildenafil appeared to increase hospitalization rates for pain in patients with SCD. This study is registered at www.clinicaltrials.gov as NCT00492531.
authors.affiliation: University of Illinois, Chicago, IL, USA.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Yovetich
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Hassell
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kato
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
authors.forename: J Simon R
authors.initials: JS
authors.lastname: Gibbs
authors.forename: Jane A
authors.initials: JA
authors.lastname: Little
authors.forename: Dean E
authors.initials: DE
authors.lastname: Schraufnagel
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Krishnamurti
authors.forename: Reda E
authors.initials: RE
authors.lastname: Girgis
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Morris
authors.forename: Erika B
authors.initials: EB
authors.lastname: Rosenzweig
authors.forename: David B
authors.initials: DB
authors.lastname: Badesch
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanzkron
authors.forename: Onyinye
authors.initials: O
authors.lastname: Onyekwere
authors.forename: Oswaldo L
authors.initials: OL
authors.lastname: Castro
authors.forename: Vandana
authors.initials: V
authors.lastname: Sachdev
authors.forename: Myron A
authors.initials: MA
authors.lastname: Waclawiw
authors.forename: Rob
authors.initials: R
authors.lastname: Woolson
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Goldsmith
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced*; D010879:Piperazines / Q000009:adverse effects*; D011687:Purines / Q000009:adverse effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects*; D014262:Tricuspid Valve Insufficiency / Q000188:drug therapy / Q000209:etiology; D014665:Vasodilator Agents / Q000009:adverse effects*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate