Friday, November 9, 2012

Tiotropium (Spiriva) increases death rates in users compared to other COPD treatments/ BMJ

Spiriva had an unusual marketing strategy when it came out:  I was told (while eating a free lunch) it was a great drug, but could take a very long time to show benefit:  therefore, give it to patients for 6 months before concluding lack of benefit.  A six month trial cost the patient about $1,000.

Six months before seeing benefit in COPD?  That sounded dodgy to me.  The similar drug ipratropium had showed benefit quickly.  Thankfully, I chose not to prescribe it.

Fast forward.  After several years of papers questioning the drug's safety, Curt Furberg et al. have published a meta-analysis in the BMJ, showing the drug increases the death rate in users.  Using the low dose, there will be an estimated 1 excess death per year per 124 users, or a 52% overall increased risk of mortality in users:
Results Five randomised controlled trials were eligible for inclusion. Tiotropium mist inhaler was associated with a significantly increased risk of mortality (90/3686 v 47/2836; relative risk 1.52, 95% confidence interval, 1.06 to 2.16; P=0.02; I2=0%). Both 10 µg (2.15, 1.03 to 4.51; P=0.04; I2=9%) and 5 µg (1.46, 1.01 to 2.10; P=0.04; I2=0%) doses of tiotropium mist inhaler were associated with an increased risk of mortality. The overall estimates were not substantially changed by sensitivity analysis of the fixed effect analysis of the five trials combined using the random effects model (1.45, 1.02 to 2.07; P=0.04), limiting the analysis to three trials of one year’s duration each (1.50, 1.05 to 2.15), or the inclusion of additional data on tiotropium mist inhaler from another investigational drug programme (1.42, 1.01 to 2.00). The number needed to treat for a year with the 5 µg dose to see one additional death was estimated to be 124 (95% confidence interval 52 to 5682) based on the average control event rate from the long term trials.
Appropriately, the question is asked:  why is this drug still on the market?

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