Article

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

Penn Cardiovascular Institute, Department of Medicine and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 423 Guardian Drive, Philadelphia, PA 19104, USA.
Circulation (impact factor: 14.74). 05/2011; 123(25):2985-93. DOI:10.1161/CIRCULATIONAHA.110.015693 pp.2985-93
Source: PubMed

ABSTRACT Pulmonary arterial hypertension (PAH) is a progressive disease that causes exercise limitation, heart failure, and death. We aimed to determine the safety and efficacy of aspirin and simvastatin in PAH.
We performed a randomized, double-blind, placebo-controlled 2×2 factorial clinical trial of aspirin and simvastatin in patients with PAH receiving background therapy at 4 centers. A total of 92 patients with PAH were to be randomized to aspirin 81 mg or matching placebo and simvastatin 40 mg or matching placebo. The primary outcome was 6-minute walk distance at 6 months. Sixty-five subjects had been randomized when the trial was terminated by the Data Safety and Monitoring Board after an interim analysis showed futility in reaching the primary end point for simvastatin. After adjustment for baseline 6-minute walk distance, there was no significant difference in the 6-minute walk distance at 6 months between aspirin (n=32) and placebo (n=33; placebo-corrected difference −0.5 m, 95% confidence interval −28.4 to 27.4 m; P=0.97) or between simvastatin (n=32) and placebo (n=33; placebo-corrected difference −27.6 m, 95% confidence interval −59.6 to 4.3 m; P=0.09). There tended to be more major bleeding episodes with aspirin than with placebo (4 events versus 1 event, respectively; P=0.17).
Neither aspirin nor simvastatin had a significant effect on the 6-minute walk distance, although patients randomized to simvastatin tended to have a lower 6-minute walk distance at 6 months. These results do not support the routine treatment of patients with PAH with these medications.

0 0
 · 
0 Bookmarks
 · 
70 Views
  • Source
    Article: Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells.
    Omar F Ali, Ellena J Growcott, Ghazwan S Butrous, John Wharton
    [show abstract] [hide abstract]
    ABSTRACT: Recent clinical data suggest statins have transient but significant effects in patients with pulmonary arterial hypertension. In this study we explored the molecular effects of statins on distal human pulmonary artery smooth muscle cells (PASMCs) and their relevance to proliferation and apoptosis in pulmonary arterial hypertension. Primary distal human PASMCs from patients and controls were treated with lipophilic (simvastatin, atorvastatin, mevastatin and fluvastatin), lipophobic (pravastatin) and nitric-oxide releasing statins and studied in terms of their DNA synthesis, proliferation, apoptosis, matrix metalloproteinase-9 and endothelin-1 release. Treatment of human PASMCs with selected statins inhibited DNA synthesis, proliferation and matrix metalloproteinase-9 production in a concentration-dependent manner. Statins differed in their effectiveness, the rank order of anti-mitogenic potency being simvastatin > atorvastatin > > pravastatin. Nevertheless, a novel nitric oxide-releasing derivative of pravastatin (NCX 6550) was effective. Lipophilic statins, such as simvastatin, also enhanced the anti-proliferative effects of iloprost and sildenafil, promoted apoptosis and inhibited the release of the mitogen and survival factor endothelin-1. These effects were reversed by mevalonate and the isoprenoid intermediate geranylgeranylpyrophosphate and were mimicked by inhibitors of the Rho and Rho-kinase. Lipophilic statins exert direct effects on distal human PASMCs and are likely to involve inhibition of Rho GTPase signalling. These findings compliment some of the recently documented effects in patients with pulmonary arterial hypertension.
    Respiratory research 01/2011; 12:137. · 3.36 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

1 event
 
4 centers
 
6-minute walk distance
 
aspirin 81 mg
 
background therapy
 
baseline 6-minute walk distance
 
causes exercise limitation
 
Data Safety
 
heart failure
 
interim analysis
 
lower 6-minute walk distance
 
patients randomized
 
placebo-controlled 2×2 factorial clinical trial
 
placebo-corrected difference −0.5
 
placebo-corrected difference −27.6
 
primary end point
 
Pulmonary arterial hypertension
 
routine treatment
 
significant effect
 
simvastatin 40 mg