COPD mortality and exacerbations in the placebo group of clinical trials over two decades: a systematic review and meta-regression.

A decreasing trend in exacerbation rates has been observed in COPD. Because mortality is linked to exacerbations, it is of interest to investigate whether a similar time trend is also present in mortality rates. We performed a systematic review of placebo groups in published randomised controlled trials. Mortality rate was modelled based on a Poisson distribution for the event counts. Adding information on mortality as well as on newly published studies on a previous database, we performed a meta-regression. Among the 56 included studies representing 14 166 patients, an annual decrease in mortality rates of 6.1% (-0.6%, 12.6%) (p=0.073) was observed. Consistent results were obtained in subgroups as well as when adjusting for potential confounders. The correlation between exacerbation rate and mortality rate was positive but weak as well as insignificant. In summary, analysis of randomised controlled trials in COPD patients showed a decrease in mortality in the placebo arms over the last two decades. This effect is comparable to the previously observed decrease in annual exacerbation rate. Albeit insignificant, our results suggest that care is needed in the design of new trials or when comparing results from trials published many years apart.

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Déclaration de conflit d'intérêts

Conflict of interest: S. Andreas reports receiving a prize from Oskar Helene during the conduct of the study; and grants and personal fees from Boehringer Ingelheim, grants from Pfizer, and personal fees from Novartis, AstraZeneca, GSK, Chiesi and Merini, outside the submitted work. Conflict of interest: C. Röver has nothing to disclose. Conflict of interest: J. Heinz has nothing to disclose. Conflict of interest: C. Taube has nothing to disclose. Conflict of interest: T. Friede reports consultancy fees from Novartis, Bayer, Janssen, Roche, Boehringer Ingelheim, Daiichi-Sankyo, Galapagos, Penumbra, Parexel, Vifor, BiosenseWebster, CSL Behring, Fresenius Kabi, Coherex Medical, LivaNova and Minoryx, outside the submitted work.