Literature DB >> 21146637

Rationale and design of a phase II clinical trial of aspirin and simvastatin for the treatment of pulmonary arterial hypertension: ASA-STAT.

Steven M Kawut1, Emilia Bagiella, Daichi Shimbo, David J Lederer, Nadine Al-Naamani, Kari E Roberts, R Graham Barr, Wendy Post, Evelyn M Horn, Russell Tracy, Paul Hassoun, Reda Girgis.   

Abstract

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease which causes exercise limitation, heart failure, and death. Aspirin and simvastatin are highly effective and safe therapies for other cardiovascular diseases characterized by platelet activation and endothelial dysfunction, but have not been formally studied in PAH.
METHODS: ASA-STAT is a phase II, randomized, double-blind, placebo-controlled 2 × 2 factorial clinical trial of aspirin and simvastatin in patients with PAH. A total of 92 subjects were to be randomized to aspirin or aspirin placebo and simvastatin or simvastatin placebo. The primary outcome is the distance walked in 6 min at 6 months after randomization. Secondary measures include brachial artery flow-mediated dilation, circulating biomarkers of platelet and endothelial function, functional class, quality-of-life, and time to clinical end points. The incidence of adverse events will be compared between treatment groups. SCREENING AND ENROLLMENT: We screened a total of 712 individuals with PAH. Sixty-five subjects were enrolled when the trial was terminated for futility in reaching the primary end point for simvastatin.
CONCLUSIONS: This study aims to determine whether aspirin or simvastatin have beneficial biologic or clinical effects in patients with PAH. The safety and side effects of these commonly prescribed cardiovascular drugs will also be assessed.
Copyright © 2010 Elsevier Inc. All rights reserved.

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Year:  2010        PMID: 21146637      PMCID: PMC3034822          DOI: 10.1016/j.cct.2010.12.005

Source DB:  PubMed          Journal:  Contemp Clin Trials        ISSN: 1551-7144            Impact factor:   2.226


  17 in total

1.  Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy.

Authors:  F Sakamaki; S Kyotani; N Nagaya; N Sato; H Oya; T Satoh; N Nakanishi
Journal:  Circulation       Date:  2000-11-28       Impact factor: 29.690

2.  The B-value: a tool for monitoring data.

Authors:  K K Lan; J Wittes
Journal:  Biometrics       Date:  1988-06       Impact factor: 2.571

3.  Microangiopathic hemolytic anemia and thrombocytopenia in primary pulmonary hypertension.

Authors:  I D Stuard; R S Heusinkveld; A J Moss
Journal:  N Engl J Med       Date:  1972-10-26       Impact factor: 91.245

4.  Sequential monitoring of clinical trials: the role of information and Brownian motion.

Authors:  K K Lan; D M Zucker
Journal:  Stat Med       Date:  1993-04-30       Impact factor: 2.373

5.  Microangiopathic hemolytic anemia and thrombocytopenia in a child with atrial septal defect and pulmonary hypertension.

Authors:  H Suzuki; M Nakasato; S Sato; S Yokoyama; M Katsuura; S Yamaki; K Hayasaka
Journal:  Tohoku J Exp Med       Date:  1997-03       Impact factor: 1.848

6.  Simvastatin as a treatment for pulmonary hypertension trial.

Authors:  Martin R Wilkins; Omar Ali; William Bradlow; John Wharton; Anne Taegtmeyer; Christopher J Rhodes; Hossein A Ghofrani; Luke Howard; Petros Nihoyannopoulos; Raad H Mohiaddin; J Simon R Gibbs
Journal:  Am J Respir Crit Care Med       Date:  2010-05-15       Impact factor: 21.405

7.  An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension.

Authors:  B W Christman; C D McPherson; J H Newman; G A King; G R Bernard; B M Groves; J E Loyd
Journal:  N Engl J Med       Date:  1992-07-09       Impact factor: 91.245

8.  A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention.

Authors:  Robert Fathi; Brian Haluska; Leanne Short; Thomas H Marwick
Journal:  Am J Med       Date:  2003-04-15       Impact factor: 4.965

9.  Simvastatin rescues rats from fatal pulmonary hypertension by inducing apoptosis of neointimal smooth muscle cells.

Authors:  Toshihiko Nishimura; Laszlo T Vaszar; John L Faul; Guohua Zhao; Gerald J Berry; Lingfang Shi; Daoming Qiu; Gail Benson; Ronald G Pearl; Peter N Kao
Journal:  Circulation       Date:  2003-09-08       Impact factor: 29.690

10.  Oxidative stress in severe pulmonary hypertension.

Authors:  Rebecca Bowers; Carlyne Cool; Robert C Murphy; Rubin M Tuder; Matthew W Hopken; Sonia C Flores; Norbert F Voelkel
Journal:  Am J Respir Crit Care Med       Date:  2003-12-30       Impact factor: 21.405

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  5 in total

1.  Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA-STAT.

Authors:  Steven M Kawut; Emilia Bagiella; David J Lederer; Daichi Shimbo; Evelyn M Horn; Kari E Roberts; Nicholas S Hill; R Graham Barr; Erika B Rosenzweig; Wendy Post; Russell P Tracy; Harold I Palevsky; Paul M Hassoun; Reda E Girgis
Journal:  Circulation       Date:  2011-05-18       Impact factor: 29.690

2.  Interleukin-6 and tumor necrosis factor-α are associated with quality of life-related symptoms in pulmonary arterial hypertension.

Authors:  Lea Ann Matura; Corey E Ventetuolo; Harold I Palevsky; David J Lederer; Evelyn M Horn; Stephen C Mathai; Diane Pinder; Christine Archer-Chicko; Emilia Bagiella; Kari E Roberts; Russell P Tracy; Paul M Hassoun; Reda E Girgis; Steven M Kawut
Journal:  Ann Am Thorac Soc       Date:  2015-03

3.  Prognostic Significance of Biomarkers in Pulmonary Arterial Hypertension.

Authors:  Nadine Al-Naamani; Harold I Palevsky; David J Lederer; Evelyn M Horn; Stephen C Mathai; Kari E Roberts; Russell P Tracy; Paul M Hassoun; Reda E Girgis; Daichi Shimbo; Wendy S Post; Steven M Kawut
Journal:  Ann Am Thorac Soc       Date:  2016-01

4.  Spironolactone in pulmonary arterial hypertension: results of a cross-over study.

Authors:  Zeenat Safdar; Adaani Frost; Arya Basant; Anita Deswal; E O'Brian Smith; Mark Entman
Journal:  Pulm Circ       Date:  2020-05-01       Impact factor: 3.017

5.  Simvastatin protects heart function and myocardial energy metabolism in pulmonary arterial hypertension induced right heart failure.

Authors:  Bi Tang; Pinfang Kang; Lei Zhu; Ling Xuan; Hongju Wang; Heng Zhang; Xiaojing Wang; Jiali Xu
Journal:  J Bioenerg Biomembr       Date:  2021-01-04       Impact factor: 2.945

  5 in total

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