Simon Teal

Endothelin antagonism and uric acid levels in pulmonary arterial hypertension: Clinical associations

BACKGROUND Elevated serum uric acid is detected in pulmonary arterial hypertension (PAH) and is associated with poor patient outcomes. High serum uric acid is an independent risk factor for cardiovascular disease and renal impairment. We analyzed the effects of endothelin receptor antagonism on serum uric acid in PAH patients participating in the Sitaxentan to Relieve Impaired Exercise (STRIDE)-2/2X trial, and the impact of uric acid on 6-minute walk distance (6MWD), time to clinical worsening (TtCW) and survival. METHODS In the 18-week, double-blind, placebo-controlled STRIDE-2 trial, 246 PAH patients were randomized and received matched placebo, sitaxentan 50 or 100 mg orally once daily, or open-label bosentan 125 mg twice daily. STRIDE-2X was a 1-year, open-label extension of STRIDE-2. RESULTS Baseline serum uric acid was similar between groups. Increased serum uric acid was a significant risk factor for 1-year mortality and TtCW. Compared with placebo, sitaxentan 50 and 100 mg and bosentan all reduced serum uric acid (p < 0.05). Reduced serum uric acid correlated with increased 6MWD (p = 0.0037). CONCLUSIONS Endothelin receptor antagonism reduces serum uric acid in PAH patients, and this reduction is associated with improved survival and longer TtCW. Further prospective studies are needed to investigate the pathogenic role of serum uric acid in PAH and its prognostic potential.

Changes in healthcare utilization and costs associated with sildenafil therapy for pulmonary arterial hypertension: a retrospective cohort study

BackgroundLittle is known concerning the degree to which initiation of sildenafil for pulmonary arterial hypertension (PAH) impacts patterns of healthcare utilization and costs.MethodsUsing a large US health insurance claims database, we identified all patients with evidence of PAH (ICD-9-CM diagnosis codes 416.0, 416.8) who received sildenafil between 1/1/2005 and 9/30/2008. Date of the first-noted prescription for sildenafil was designated the “index date,” and claims data were compiled for all study subjects for 6 months prior to their index date (“pretreatment”) and 6 months thereafter (“follow-up”); patients with incomplete data during either of these periods were excluded. Healthcare utilization and costs were then compared between pretreatment and follow-up for all study subjects.ResultsA total of 567 PAH patients were identified who began therapy with sildenafil and met all other study entry criteria. Mean (SD) age was 52 (10) years; 73% were women. Healthcare utilization was largely unchanged between pretreatment and follow-up, the only exceptions being decreases in the mean number of emergency department visits (from 0.7 to 0.5 per patient; p < 0.01) and the percentage of patients hospitalized (from 35% to 29%; p = 0.01). The mean cost of all PAH-related medication was

Cumulative Distribution Functions of Sildenafil Citrate on Exercise Capacity and Hemodynamic Function in Children with Pulmonary Arterial Hypertension

7139 during pretreatment and

Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension

14,095 during follow-up (sildenafil cost during follow-up = 

Incidence of subdural hematoma in patients with pulmonary arterial hypertension (PAH) in two randomized controlled clinical trials

5236); exclusive of PAH-related medications, however, total healthcare costs decreased modestly (from

Item Refinement and Psychometric Testing of a Novel Survey for Evaluating Patient Perception and Preference for Haemophilia a Treatment

30,104 to

A Cost-Effectiveness Analysis Of Sildenafil For The Treatment Of Pulmonary Arterial Hypertension In Europe

27,605) (p < 0.01 for all comparisons).ConclusionsThe cost of sildenafil therapy may be partially offset by reductions in other healthcare costs.

PRS26 A Cost-Effectiveness Analysis of Sildenafil for the Treatment of Pulmonary Arterial Hypertension in Europe

Background: Pulmonary Arterial Hypertension (PAH) is an ultimately fatal condition characterized by reduced exercise capacity and impaired hemodynamic parameters. Although these relationships are well described in adults with PAH, they are not characterized in pediatric populations. Methods: Children (aged 1–17 years) with PAH received 16 weeks of randomized, double-blind treatment with sildenafil or placebo. The primary outcome measure, peak VO2 (PVO2), was assessed using cardiopulmonary exercise testing in children developmentally capable of exercise. Secondary measures (for all patients) included Mean Pulmonary Arterial Pressure (mPAP), Pulmonary Vascular Resistance Index (PVRI), and cardiac index. Cumulative Distribution Functions (CDFs) plotted the cumulative percentage of patients against percentage changes (and also numeric changes) from baseline to week 16 in outcome measures. The Kolmogorov-Smirnov test assessed the difference in separation between sildenafil CDF and placebo CDF. Results: Of 234 randomized and treated children, 106 were developmentally able to exercise and 148 to 221 provided non-exercise endpoint data. Significant differences between the CDFs were observed for sildenafil (all doses combined) vs. placebo for percentage changes in PVO2, mPAP, and PVRI (P=0.02, 0.01, and 0.001, respectively) but not for cardiac index (P=0.14). Fifty-eight of 77 (75%) sildenafil-treated children had increases in the percentage change in PVO2 vs. 13 of 29 (45%) placebo-treated children. Across all measures, a similar pattern of results was obtained when numeric (rather than percentage) changes were assessed. Conclusions: Cumulative distribution functions, which incorporate the entire distribution of responses, can enhance clinical interpretation of outcome measures. By CDF analysis, an enhanced profile of sildenafil (vs. placebo) was observed, indicating improvement in PVO2, mPAP and PVRI, but not cardiac index, in children with PAH. *Corresponding author: Joseph C Cappelleri, Pfizer Inc, 445 Eastern Point Road, MS 8260-2502, Groton, CT, USA 06340, Tel: +1 860 441 8033; Fax: +1 860 686 5139; E-mail: joseph.c.cappelleri@pfizer.com Received March 26, 2013; Accepted April 20, 2013; Published April 22, 2013 Citation: Cappelleri JC, Hwang LJ, Mardekian J, Teal SA, Mychaskiw MA (2013) Cumulative Distribution Functions of Sildenafil Citrate on Exercise Capacity and Hemodynamic Function in Children with Pulmonary Arterial Hypertension. J Pulmon Resp Med S4: 002. doi:10.4172/2161-105X.S4-002 Copyright: