"Tiotropium and Outcomes in Chronic Obstructive Pulmonary Disease". The New England Journal of Medicine. 2008. 359(15):1543-1554. PubMed • Full text • PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Funding
10 Further Reading

Clinical Question

In patients with chronic obstructive pulmonary disease (COPD), does long-term therapy with tiotropium improve clinical outcomes?

Bottom Line

In patients with COPD, therapy with tiotropium over a 4-year period improved lung function, quality of life, and exacerbations but did not significantly slow the rate of decline in FEV1.

Major Points

Guidelines

As of the time of the study, guidelines did not specifically recommend the use of tiotropium for altering disease progression, though it may be used for symptomatic relief.

Design

- Multicenter, double-blind, placebo-controlled, parallel-group trial
- N=5,993 patients with moderate-to-very-severe COPD
- Tiotropium (n=2,987) vs. Placebo (n=3,006)
- Setting: 490 investigational centers in 37 countries
- Enrollment: January 2003 to March 2004
- Analysis: Intention-to-treat
- Follow-up: 4 years
- Primary outcome: Yearly rate of decline in mean FEV1 before and after bronchodilation from day 30 until completion of double-blind treatment

Population

Inclusion Criteria
- Diagnosis of COPD
- Age ≥40 years
- Smoking history of ≥10 pack-years
- Postbronchodilator FEV1 ≤70% predicted and FEV1/FVC ratio ≤70% after bronchodilation

Exclusion Criteria
- Asthma history
- COPD exacerbation or respiratory infection within 4 weeks before screening
- History of pulmonary resection
- Use of supplemental oxygen >12 hours/day
- Coexisting illness impacting participation or results

Baseline Characteristics
- Mean age: 65±8 years
- 75% male, 30% current smokers
- Mean postbronchodilator FEV1: 1.32±0.44 liters (48% predicted)

Interventions

- Patients received either 18 μg of tiotropium or matching placebo once daily delivered through the HandiHaler inhalation device

Outcomes

Primary Outcome
- No significant differences between groups in the rate of decline in the mean FEV1 before or after bronchodilation from day 30 to the end of the study-drug treatment

Secondary Outcomes
- Tiotropium group maintained mean FEV1 and FVC improvements throughout the trial compared to placebo (P<0.001)
- SGRQ scores were better in the tiotropium group throughout the 4-year period (P<0.001)
- Delay in time to the first exacerbation and hospitalization for an exacerbation with tiotropium

Funding

Supported by Boehringer Ingelheim and Pfizer.

Further Reading