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


METHODS
A 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%.


RESULTS
43 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 (FEV(1)) higher (p<0.01) and sputum eosinophils lower with simvastatin compared with placebo (9.5% compared with 25.4%, p=0.033).


CONCLUSIONS
Simvastatin 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 number ACTRN12606000531516.
Cowan
Douglas C
DC
Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Cowan
Jan O
JO
Palmay
Rochelle
R
Williamson
Avis
A
Taylor
D Robin
DR
D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*; D055815:Young Adult
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000068298:Fluticasone