Inhaled Corticosteroids and Mortality in COPD: Recommendation

The reduction in all-cause mortality that we found was of similar magnitude to that observed in other cohort studies and was present in time-dependent analyses that were comparable to those that produced negative results. Randomized trials of ICSs in COPD patients have not shown significant mortality effects, but pooled data from these trials have shown a mortality benefit of similar magnitude to ours. We believe that it is likely that ICSs do indeed reduce mortality in COPD patients, but further evidence from randomized trials would be helpful in resolving the controversy.
Though death due to COPD itself tended to be reduced by ICS therapy, the effect was weaker than that on cardiovascular death. The relatively weak effect on death due to COPD was compatible with the results of several carefully done trials showing that therapy with ICSs did not alter the rate of decline of lung function in COPD patients. In regard to cardiovascular mortality, our results are in agreement with reports indicating that therapy with ICSs is associated with a decreased risk of myocardial infarction. The mechanism for the reduction in cardiovascular deaths associated with ICSs is not clear. Possible explanations include reductions in COPD exacerbations, which produce hypoxia and instability that may predispose to cardiovascular events, reduction in systemic inflammation or reduced adaptive immune response.
COPD patients treated with bronchodilators and without ICSs had higher mortality rates than those treated with neither. This is compatible with bron-chodilator use being a surrogate for disease severity; that is, people who received bronchodilators were sicker than those who did not. However, the fact that patients who received ICSs, who also received bronchodilators, had death rates that were similar to patients who received neither, might be interpreted as suggesting that ICSs reduced mortality by canceling a negative effect of bronchodilators. There is no evidence that bronchodilators increase all-cause mortality in COPD patients, but there have been several studies that suggest that bronchodila-tors may increase the risk of cardiovascular events. It is thus possible that bronchodilator therapy is associated with cardiovascular events in COPD patients, and that ICSs negate or reduce this effect. Such an influence would be compatible with the evidence that the influence of ICSs on mortality appears to be a short-term effect that is best seen in the 30 days after the receipt of the agents.

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