Simvastatin in the treatment of asthma: lack of steroid-sparing effect

• Published in: Thorax Vol. 65; no. 10; pp. 891 - 896
• Main Authors: Cowan, Douglas C, Cowan, Jan O, Palmay, Rochelle, Williamson, Avis, Taylor, D Robin
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.10.2010; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adult; Aged; Androstadienes - administration & dosage; Anti-Asthmatic Agents - therapeutic use; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Asthma; Asthma - drug therapy; asthma pharmacology; Biological and medical sciences; Cardiology. Vascular system; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug dosages; Drug Therapy, Combination; eosinophil; Epidemiologic Methods; Female; Fluticasone; Glucocorticoids - administration & dosage; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Inhalers; Male; Medical sciences; Middle Aged; Nitric oxide; phenotype; Pneumology; Questionnaires; simvastatin; Simvastatin - therapeutic use; Spirometry; Steroids; Survival analysis; Young Adult; New Zealand; Lung disease; Corticosteroid; Enzyme; Respiratory disease; Simvastatin; Enzyme inhibitor; Statin derivative; Hypocholesterolemic agent; Asthma; Drug conversion; Treatment; Shutdown; HMG-CoA reductase inhibitor; Hydroxymethylglutaryl-CoA reductase; Bronchus disease; Anesthesia; Obstructive pulmonary disease; Oxidoreductases; Circulatory system; Immunosuppressive agent; Cardiology; Antilipemic agent
• ISSN: 0040-6376; 1468-3296; 1468-3296
• DOI: 10.1136/thx.2010.138990

BackgroundStatins have anti-inflammatory actions which in theory are potentially beneficial in asthma. Small trials have failed to show a significant benefit, but a systematic study to evaluate the steroid-sparing effect of statin treatment has not been carried out.MethodsA randomised, placebo-controlled, crossover trial was conducted of simvastatin 40 mg at night with simultaneous stepwise reduction of fluticasone propionate dose until loss of control occurred, followed by an increase until regain of control (‘minimum’ dose required) in 51 patients with asthma and sputum eosinophils (steroid-free) ≥2%.Results43 patients completed the study. There was no significant difference in ‘minimum’ inhaled corticosteroid (ICS) dose requirement between simvastatin and placebo: (median (IQR) 50 μg daily (0–250) vs 100 μg daily (0–250), p=0.931). ‘Minimum’ dose distribution was similar (p=0.269). The fluticasone dose at which loss of control occurred did not differ significantly between simvastatin and placebo (p=0.404). In patients with loss of control in both treatment arms, fluticasone dose at loss of control was similar with simvastatin and placebo (median (IQR) 50 μg daily (0–100) for both, p=0.620). In those patients who reached 0 μg/day (n=18), Astma Control Questionnaire (ACQ) was lower (p=0.037), forced expiratory volume in 1 s (FEV1) higher (p<0.01) and sputum eosinophils lower with simvastatin compared with placebo (9.5% compared with 25.4%, p=0.033).ConclusionsSimvastatin does not have clinically important steroid-sparing effects in patients with eosinophilic asthma. In the absence of steroid, simvastatin is associated with minor improvements in symptoms and lung function, and a reduction in sputum eosinophils.Clinical trial numberACTRN12606000531516.