Landmark UPLIFT Study Reaffirms the Safety of Spiriva (tiotropium) in Patients With Chronic Obstructive Pulmonary Disease

Leuven, Belgium (ots/PRNewswire) -

- For Media Outside US and Canada

- 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, randomised, 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-centre,
randomised, 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
standardised 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
0.76, 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 Editors:

The UPLIFT study was sponsored by Boehringer Ingelheim and Pfizer

http://www.uzleuven.be

ots Originaltext: UZ Leuven
Im Internet recherchierbar: http://www.presseportal.de

Contact:
For more information: Prof. dr. Marc Decramer, head of pneumology
(University Hospitals Leuven), Mobile: +32-475-57-06-87