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Cardiovascular Safety of Tiotropium in Patients With COPD

      Background

      The clinical trial safety database for tiotropium has been augmented with a 4-year trial in patients with COPD, which provides an opportunity to better evaluate the cardiovascular (CV) profile of tiotropium.

      Methods

      Trials with the following criteria were considered: ≥ 4 weeks, randomized, double-blind, parallel-group, placebo-controlled. Inclusion/exclusion criteria were similar, including spirometry-confirmed COPD, ≥ 10 pack-year smoking, and age ≥ 40 years. Adverse events were collected throughout each trial using standardized case report forms. Incidence rates (IRs) were determined from the total number of patients with an event divided by total time at risk. Rate ratios (RRs) and 95% CI for tiotropium/placebo were calculated. IRs were determined for all-cause mortality and selected CV events, including a composite CV end point encompassing CV deaths, nonfatal myocardial infarction (MI), nonfatal stroke, and the terms sudden death, sudden cardiac death, and cardiac death.

      Results

      There were 19,545 patients randomized: 10,846 (tiotropium) and 8,699 (placebo) from 30 trials. Mean FEV1 = 1.15 ± 0.46 L (41 ± 14% predicted), 76% men, mean age = 65 ± 9 years. Cumulative exposure to study drug was 13,146 (tiotropium) and 11,095 (placebo) patient-years. For all-cause mortality, the IR was 3.44 (tiotropium) and 4.10 (placebo) per 100 patient-years (RR [95% CI] = 0.88 [0.77–0.999]). IR for the CV end point was 2.15 (tiotropium) and 2.67 (placebo) per 100 patient-years (RR [95% CI] = 0.83 (0.71–0.98]). The IR for the CV mortality excluding nonfatal MI and stroke was 0.91 (tiotropium) and 1.24 (placebo) per 100 patient-years (RR [95% CI] = 0.77 [0.60–0.98]). For total MI, cardiac failure, and stroke the RRs (95% CI) were 0.78 (0.59–1.02), 0.82 (0.69–0.98), and 1.03 (0.79–1.35), respectively.

      Conclusion

      Tiotropium was associated with a reduction in the risk of all-cause mortality, CV mortality, and CV events.
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      Linked Article

      • Anticholinergic Drugs for the Treatment of COPD Are Safe… Are They?
        CHESTVol. 137Issue 1
        • Preview
          COPD is increasingly recognized as a complex systemic disorder with a whole range of comorbidities, especially cardiovascular, contributing significantly to COPD morbidity and mortality.1 Among the most frequently prescribed inhaled medications for this disorder are anticholinergic agents, such as short-acting ipratropium bromide, available for 20 years, and the long-acting drug tiotropium bromide, introduced in 2002, which has been shown to improve airflow, hyperinflation, exercise tolerance, exacerbations of COPD, and health-related quality of life with once-daily dosing2–8 in patients with COPD.
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