Association of tiotropium use and the risk of adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials

Background Tiotropium have been recommended as first-line maintenance therapy for chronic obstructive pulmonary disease (COPD) to reduce the frequency, duration, and severity of exacerbations and improve quality of life. Recently, it was reported that tiotropium use might link to cardiovascular risk in COPD patients. But it is controversial. We aimed to clarify the associations between tiotropium use and cardiovascular risk in patients with COPD. Methods We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials.gov to identify potentially relevant articles. We included randomized controlled trials of any inhaled tiotropium versus non-anticholinergic treatment for COPD, with reporting of cardiovascular events as an adverse event. We conducted meta-analyses by the Peto and Mantel-Haenszel approaches with corresponding 95% CIs. Results Our work included 20 RCTs with more than 27,699 subjects. Pooled results indicated that tiotropium treatment did not increase the risk of cardiovascular events (Peto OR, 0.97, 95% CI, 0.84–1.12; I 2 = 0%), overall mortality (RD, 0.00, 95% CI, − 0.00–0.01; I 2 = 68%), and cardiovascular mortality (Peto OR, 1.58, 95% CI, 0.92–2.74; I 2 = 0%) compared with controls. Then, subgroup analysis was performed according to the type of controls. The pooled results were consistent with the above (tiotropium vs LABA: Peto OR, 0.98, 95% CI, 0.81–1.19; I 2 = 17%) (tiotropium vs placebo: Peto OR, 0.92, 95% CI, 0.75–1.44; I 2 = 15%). In addition, there was also no association between cardiovascular risk and duration of tiotropium treatment. Conclusions Inhaled tiotropium does not increase the risk of cardiovascular events and cardiovascular mortality in patients with COPD.