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Cardiovascular Safety of Tiotropium in Patients With COPD.
Chest. 2009 Jul 10;
Authors: Celli B, Decramer M, Leimer I, Vogel U, Kesten S, Tashkin DP
BACKGROUND: The clinical trial safety database for tiotropium has been augmented with a 4-year trial in COPD patients, which provides an opportunity to better evaluate the cardiovascular(CV) profile of tiotropium. METHODS: Trials with the following criteria: >/=4 weeks, randomized, double-blind, parallel-group, placebo-controlled. Inclusion/exclusion criteria were similar including spirometry confirmed COPD, >/=10 pack-year smoking, age >/= 40 years. Adverse events were collected throughout each trial using standardized case report forms. Incidence rates(IR) were determined from the total number of patients with an event divided by total time at risk. Rate ratios (RR) and 95%CI for tiotropium/placebo were calculated. IR were determined for all-cause mortality and selected CV events including a composite CV endpoint encompassing CV deaths, nonfatal myocardial infarction (MI), nonfatal stroke, and the terms sudden death, sudden cardiac death and cardiac death. RESULTS: 19,545 patients randomized, 10,846(tiotropium) and 8,699(placebo) from 30 trials. Mean FEV(1)=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 endpoint 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 RR(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, cardiovascular mortality and cardiovascular events.
PMID: 19592475 [PubMed - as supplied by publisher]