Landmark UPLIFT study reaffirms the safety of Spiriva (tiotropium) in patients with
Chronic Obstructive Pulmonary Disease

Prof. dr. Marc Decramer, head of pneumology of the University Hospitals Leuven, is lead investigator
of the international UPLIFT study investigating treatment of COPD patients with tiotropium.Today he
elaborates on the results.

Placebo-controlled, randomized, double-blind clinical trials provide the most comprehensive and
strongest evidence of a drug’s safety profile. The long-term exposure of thousands of patients with
COPD to tiotropium in the UPLIFT study, which has closely and rigorously evaluated both efficacy and
safety, provides a reaffirmation of the tiotropium safety profile and strong evidence that tiotropium
does not increase the risk of all-cause or cardiovascular mortality.

UPLIFT (Understanding Potential Long-term impacts on Function with Tiotropium) is a four-year
landmark multinational, multi-center, randomized, double-blind clinical COPD study trial involving
5,993 patients from 37 countries across the globe. This ambitious study investigated the benefits of
Spiriva versus placebo over four years in a real-life treatment approach, allowing for use of all
respiratory medications throughout the trial, other than inhaled anticholinergics.

The data from UPLIFT indicate that tiotropium does not increase the risk of death, cardiovascular
death, myocardial infarction and stroke. Furthermore, examination of all serious cardiac and all
serious lower respiratory tract adverse events indicates that tiotropium is associated with a decreased
risk of experiencing a serious adverse event in these organ classes.

In UPLIFT, there were 2,986 tiotropium treated patients and 3006 placebo treated patients, who
contributed to 9,468 and 8,746 patient years exposure respectively. Safety was monitored closely
through a standardized adverse reporting process. An independent data and safety monitoring
committee reviewed data throughout the trial and an independent committee adjudicated primary
cause of death.

There was no evidence of an increased risk of death during the study. During treatment, fatal events
occurred in 381 patients (12.8%) in the tiotropium-treated group and 411 (13.7%) in the placebo group
(a 16% risk reduction in the tiotropium group, hazard ratio 0.84; 95% CI, 0.73 to 0.97). An intent to
treat analysis was performed by including vital status information (i.e. alive, dead, and the cause of
death) on patients who prematurely discontinued the study (i.e. no longer taking study drug). During
the protocol defined treatment period (until day 1440), the hazard ratio was 0.87; 95% CI 0.72, 0.99).
The corresponding hazard ratio up until the 30 day follow-up period (day 1470) was 0.89 (0.79, 1.02.

A specific analysis was conducted for cardiovascular death. There was no evidence for an
increased risk of cardiovascular death during treatment (risk ratio 0.73, 95% CI 0.56, 0.95).
As myocardial infarction and stroke have been discussed, we have specifically examined the
risk for these events. Myocardial infarction developed in 67 patients in the tiotropium group
and 85 in the placebo group (relative risk, 0.73; 95% CI 0.53, 1.00), and stroke developed in 82 in the
tiotropium group and 80 in the placebo group (relative risk, 0.95; 95% CI 0.70, 1.29).

For further support of the safety of tiotropium, we have examined serious adverse events under the
organ classes of cardiac and lower respiratory disorders. For total serious cardiac adverse events, the
relative risk for tiotropium compared to placebo was 0.84 (95% CI 0.73, 0.98). For total serious lower
respiratory tract adverse events relative risk for tiotropium verses placebo was 0.84 (95% CI, 0.77,
0.92).

Full safety and efficacy data on the UPLIFT study will be presented at the upcoming Annual Meeting of
the European Respiratory Society in Berlin on October 5, 2008.

Note to the Editor: The UPLIFT study was sponsored by Boehringer Ingelheim and Pfizer

-------------------------------------------------------------------------------------------------
For more information
prof. dr. Marc Decramer, head of pneumologie (University Hospitals Leuven)
Mobile: 0032 475 57 06 87
UZ Leuven | Herestraat 49 | B - 3000 Leuven | www.uzleuven.be
University Hospitals Leuven