Rosuvastatin and vascular dysfunction markers in pulmonary arterial hypertension: a placebo-controlled study

Abstract

We investigated whether chronic rosuvastatin administration could improve the abnormalities of the circulating levels of vascular dysfunction markers in pulmonary arterial hypertension (PAH). Sixty patients, aged 13 to 60 years, with idiopathic (N = 14) or congenital heart disease-associated PAH (N = 46) were equally but randomly assigned to rosuvastatin treatment (10 mg a day, orally) or placebo for 6 months in a blind fashion. Plasma levels of P-selectin, tissue-plasminogen activator and its inhibitor as well as von Willebrand factor antigen were measured by enzyme-linked immunoassay before and after 1, 3, and 6 months of treatment. Baseline levels of biomarkers were elevated (68, 16, 45 and 46% increase relative to controls, for P-selectin, von Willebrand factor antigen, tissue-plasminogen activator and its inhibitor, respectively; P < 0.001). P-selectin values at baseline, 1, 3, and 6 months were 39.9 ± 18.5, 37.6 ± 14.6, 34.8 ± 14.6, and 35.4 ± 13.9 ng/mL, respectively, for the rosuvastatin group and 45.7 ± 26.8, 48.0 ± 26.9, 48.1 ± 25.7, and 45.7 ± 25.6 ng/mL for the placebo group. The P-selectin level was lower in the rosuvastatin group compared with placebo throughout treatment (P = 0.037, general linear model). A trend was observed towards a decrease in tissue-plasminogen activator in the statin group (16% reduction, P = 0.094), with no significant changes in the other markers. Since P-selectin is crucial in inflammation and thrombosis, its reduction by rosuvastatin is potentially relevant in the pathophysiological scenario of PAH.

Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

“…The patient population consisted of 46 patients from a previous study of 60 consecutive individuals with PAH who were randomly assigned to 6-month rosuvastatin or placebo treatment in order to investigate the effects of the statin on endothelial dysfunction markers (8). In the initial study, the first patient was enrolled in July 2005; in the present study, the follow-up was terminated in February 2010.…”

Statins may be beneficial for patients with pulmonary hypertension secondary to lung diseases

“…From these, 10 RCTs comparing the treatment effects of statins with control in PH population were identified (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). As shown in Figure 1, 6 RCTs completely fulfilled the criteria for consideration and were further included in this meta-analysis (20)(21)(22)(23)(24)(25).…”

“…Among these statin-PAH RCTs, the only positive change in clinical outcomes was reported by Wilkins et al, who showed a small and early decrease in right ventricular mass with simvastatin use, but this is transient which was not maintained at 1 year (18). Another clinical trial showed reduced P-selectin concentration in PAH patients receiving rosuvastatin, however, this did not result in an advantage in exercise capacity (17). Kawut et al even implied that simvastatin may have reduced the 6-minute walk distance and lead to more dyspnea (19).…”

Atorvastatin in Pulmonary Arterial Hypertension (APATH) study

“…The results of two small randomised clinical studies of simvastatin in human PAH have been disappointing with no evidence of an improvement in 6-min walk distance [20,21]. A study with rosuvastatin has reported a sustained reduction in P-selectin levels and a small (15 m) improvement in 6-min walk distance at 6 months in a small mixed cohort of patients with pulmonary hypertension of different aetiologies [22].…”