Risk of myocardial infarction and cardiovascular death associated with inhaled corticosteroids in COPD

Abstract

The effect of long-term inhaled corticosteroid (ICS) use on myocardial infarction (MI) and cardiovascular (CV) death in chronic obstructive pulmonary disease (COPD) remains uncertain. We conducted a systematic search of MEDLINE, EMBASE, ISI, regulatory documents and manufacturers' trial registries for long-term (>24 weeks duration) randomised controlled trials (RCTs) or controlled observational studies reporting on CV outcomes or death with ICS use in COPD. A fixed effects model was used to calculate the relative risks (RRs) and 95% CIs. 23 RCTs with 24-160 weeks of follow-up were included. In the RCTs, ICS were not associated with a significantly reduced risk of MI (RR 0.95, 95% CI 0.73-1.23; p = 0.68, I(2) = 0%), CV death (RR 1.02; 95% CI 0.81-1.27; p = 0.89, I(2) = 0%), or mortality (RR 0.96, 95% CI 0.86-1.07; p = 0.43, I(2) = 0%). In the observational studies, ICS use was associated with a significant reduction in CV death (two studies: RR 0.79, 95% CI 0.72-0, 86; p <0.0001, I(2) = 44%) and mortality (11 studies: RR 0.78, 95% CI 0.75-0.80; p<0.001, I(2) = 33%). Publication bias via funnel plot asymmetry was noted for mortality in the observational studies (Egger test, p = 0.05). We conclude that while observational studies suggest that ICS may potentially confer CV or mortality benefit, RCTs failed to show any significant effect of ICS therapy on MI or CV death. These conflicting findings need to be clarified through further research.