A recent safety review indicated a non-significant increase in all-cause mortality when treatment was compared with placebo.
This review included data from five randomised controlled trials involving 6,522 participants. The studies were of at least 30 days duration and all compared active treatment with placebo. The studies also examined two different doses of tiotropium, 5micrograms daily and 10micrograms daily. 5micrograms daily is the current recommended dose.
The tiotropium mist inhaler was associated with a significantly increased risk of death (Relative risk 1.52, 95% CI 1.06-2.16, p=0.02). The increase in risk was observed with both study doses and remained present when the three year-long studies were analysed separately. It is estimated that for every 124 patients treated for a year with the inhaler instead of placebo it would be expected to observe one additional death (NNT 124, 95% CI 52 - 5682).
The authors conclude that "clinicians should inform patients about the possibility of this increased risk and exercise caution when prescribing tiotropium mist inhaler".
This analysis does have limitations mainly arising from the study data quality. This analysis did not have access to individual patient data to allow a cause specific mortality analysis or a time to event analysis. Additionally, the included studies varied in duration, drug dose used and the population studied.
Action: Clinicians should be aware of this study. It may be prudent to reserve use of the mist inhaler to patients who cannot tolerate the dry powder device. Patients who are prescribed the mist inhaler should also be advised of the possibility of an increased risk of death.
|« SMC Update - June 2011||Top Tips for Safer Prescribing »|