FDA ( Food and Drug Administration ) stated that Boehringer Ingelheim, the maker of Spiriva HandiHaler ( Tiotropium bromide ), had conducted a pooled analysis of 29 trials that suggested a small excess risk of stroke ( 2 cases per 1000 ) with Tiotropium bromide over placebo.
FDA has now received preliminary data from UPLIFT ( Understanding the Potential Long-Term Impacts on Function with Tiotropium ), a large, 4-year, placebo controlled clinical trial with Spiriva HandiHaler in approximately 6000 patients with chronic obstructive pulmonary disease ( COPD ). The preliminary results of UPLIFT reported by Boehringer Ingelheim to the FDA showed that there was no increased risk of stroke with Tiotropium bromide compared to placebo.

Two recent publications reported increased risk for mortality and/or cardiovascular events in patients who received Tiotropium or inhaled anticholinergics. Both studies examined cardiovascular outcomes. Singh et al ( JAMA 2008 ) performed a systematic review and meta-analysis of 17 clinical trials enrolling 14,783 patients treated with inhaled anticholinergic drugs used for the treatment of chronic obstructive lung disease.
Lee et al ( Annals of Internal Medicine 2008 ) performed a case-control study of 32,130 patients ( 320,501 controls ) treated with inhaled medications, including an anticholinergic, for the treatment of chronic obstructive lung disease.

Spiriva HandiHaler contains Tiotropium bromide and is used to treat bronchospasm associated with chronic obstructive pulmonary disease.

Boehringer Ingelheim reported to the FDA that it has conducted an analysis of the safety data from 29 placebo controlled clinical studies ( pooled analysis ). In 25 of the clinical studies, patients were treated with Spiriva HandiHaler. In the other 4 clinical studies patients were treated with another formulation of Tiotropium approved in Europe, Spiriva Respimat. The 29 clinical studies included approximately 13,500 patients with COPD.
Based on data from these studies, the preliminary estimates of the risk of stroke are 8 patients per 1000 patients treated for one year with Spiriva, and 6 patients per 1000 patients treated for one year with placebo. This means that the estimated excess risk of any type of stroke due to Spiriva is 2 patients for each 1000 patients using Spiriva over a one year period.

It is important to interpret these preliminary results with caution. FDA has not confirmed these analyses. Pooled analyses can provide early information about potential safety issues. However, these analyses have inherent limitations and uncertainty that require further investigation using other data sources.

Spiriva HandiHaler is an effective medicine that is indicated for the long-term, once daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease ( COPD ), including chronic bronchitis and emphysema.

Source: FDA, 2008

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