To the Editor: The meta-analysis of inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease (COPD) by Dr Singh and colleagues1 successfully collected unpublished data and combined it with published studies. However, a 4-year randomized controlled trial involving 5993 patients (Understanding Potential Long-term Impacts on Function With Tiotropium [UPLIFT])2 that was published shortly after this meta-analysis showed no evidence of an increased risk of cardiovascular adverse events with the use of tiotropium. One possible explanation that should be considered for this discordance is publication bias, as might be suggested by a funnel plot.
Oba Y. Risk of Major Adverse Cardiovascular Events With Inhaled Anticholinergics in Patients With Chronic Obstructive Pulmonary Disease. JAMA. 2009;301(12):1223-1226. doi:10.1001/jama.2008.947