title: Tiotropium formulations and safety: a network meta-analysis.
abstract: Tiotropium is now deliveredviatwo different inhaler devices: the original Handihaler 18 μg once daily, which uses a powder formulation; and the newer Respimat Soft Mist Inhaler (SMI) 5 μg once daily. It has been questioned whether the two devices can be assumed to have the same safety profile, although the TIOSPIR trial showed that tiotropium when administeredviaRespimat SMI 5 μg is not less safe than Handihaler 18 μg. Therefore, we have carried out a safety evaluation of tiotropium Handihaler 18 µgversustiotropium Respimat SMI 5 µg and 2.5 µg,viasystematic review and network meta-analysis of the currently available clinical evidence. The results of our meta-analysis with an extremely large number of patients analysed demonstrate that the safety profile of tiotropium HandiHaler is generally superior to that of tiotropium Respimat SMI, although no statistical difference was detected between these two devices. However, the SUCRA analysis favoured tiotropium Respimat SMI with regards to serious adverse events (AEs). We do not believe that using Respimat SMI rather that HandiHaler exposes patients to higher risks of real AEs. Rather, we believe that there may be a different cardiovascular (CV) response to muscarinic receptors blockage in individual patients. Therefore, it will be essential to make all possible efforts to proactively identify patients at increased risk of CV AEs when treated with tiotropium or another antimuscarinic drug.
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Luigino
authors.initials: L
authors.lastname: Calzetta
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rogliani
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Matera
keywords: COPD; handihaler; meta-analysis; respimat SMI; safety; tiotropium