Michele TM, Pinheiro S, Iyasu S.
US Food and Drug Administration, Silver Spring, MD, USA.
N Engl J Med 2010;363:1097–9.
Editor’s note: Tiotropium was approved in the US by the Food and Drug Administration (FDA) in 2004 as the first long-acting anticholinergic bronchodilator for the treatment of patients with chronic obstructive pulmonary disease (COPD). The drug was not only associated with sustained bronchodilation over a 24-h period, but also appeared to reduce COPD exacerbations. However, a meta-analysis published 2 years ago led to concerns over the safety of inhaled anticholinergic agents in the treatment of COPD, particularly regarding an increase in the rate of adverse cardiovascular events (JAMA 2008;300:1439–50). However, the meta-analysis combined data on short-acting anticholinergics and a long-acting anti-cholinergic, tiotropium. Shortly after the results of this meta-analysis were released, the UPLIFT (Understanding Potential Long-Term Impacts on Function with Tiotropium) study, a 4-year study of tiotropium versus placebo in the treatment of COPD, was published; the results showed no evidence of an increase in cardiovascular risk with tiotropium in these patients (N Engl J Med 2008;359:1543–54). The FDA convened an expert panel to assess the implications of these data. The conclusions of their review are discussed in the current article. The consensus was that the UPLIFT study superseded the previous meta-analysis and that the results of the UPLIFT study clearly showed the cardiovascular safety of tiotropium. They make the important general point that clinicians should use measured restraint during their evaluations to ensure that safe drugs remain on the market.