The Utility of Tiotropium Among Patients With COPD: An Update of a Meta-analysis of Randomized Controlled Trials (UTAC Update)

Abstract

Background Tiotropium is a recently developed inhaled anticholinergic, used at once-daily dosing in the management of COPD. Previous studies have hinted that long-term use may lead to an increased risk for cardiovascular mortality. In 2010, the US-FDA issued a statement indicating the cardiovascular safety of Tiotropium based on the UPLIFT trial (2008), the largest and longest placebo-controlled trial on Tiotropium. However, there is still question on Tiotropium's cardiovascular safety, especially in comparison to active treatment, particularly, inhaled long-acting beta-agonists. Objectives We determined the efficacy of long-term tiotropium use on clinical endpoints such as mortality, exacerbations, and hospitalizations compared to inhaled LABAs among patients with stable moderate to severe COPD. Methodology RCTs were identified from electronic databases such as PubMed, Cochrane Library, Ovid, Herdin, Clinicaltrials.gov and Google Scholar. Relevant studies and reviews were also hand-searched. RCTs among patients with COPD comparing Tiotropium monotherapy with inhaled LABAs with at least 6 months follow-up were selected. Data on all-cause mortality, mortality from pulmonary and from cardiovascular causes, rates of hospitalizations and exacerbations were identified. The date of last search is September 7, 2012. Two independent investigators evaluated and extracted relevant data, which were analyzed using Cochrane Review Manager 5.1. Results From 495 titles and abstracts, 5 clinical trials with a total of 10,759 patients met inclusion criteria. Tiotropium did not reduce all-cause mortality (RR 0.83 95%CI 0.40-1.70), mortality from respiratory causes (RR 0.70 95%CI 0.40-1.25), and mortality from cardiovascular causes (RR 1.57 95%CI 0.86- 2.85). Tiotropium significantly decreased the risk for exacerbations (RR 0.91 95%CI 0.85-0.98), and exhibited a trend towards decreased hospitalizations (RR 0.78 95%CI 0.61-1.00). Conclusions Tiotropium did not reduce all-cause mortality, mortality from pulmonary causes, and mortality from cardiovascular causes compared to inhaled LABAs. Tiotropium significantly decreased the risk for exacerbations, and showed trend towards possible decreased hospitalizations.