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Inhaled antimuscarinic drugs: cardiovascular toxicity.

Inhaled antimuscarinic drugs have modest symptomatic efficacy in patients with chronic obstructive pulmonary disease (COPD). They also have several atropinic adverse effects, including mydriasis, visual disorders, dry mouth, constipation, micturition difficulties and tachycardia. In March 2008, the US Food and Drug Administration reported an increased frequency of stroke in COPD patients receiving tiotropium in clinical trials. A metaanalysis of 17 double-blind randomised trials in 13 645 patients with COPD showed a statistically significant increase in the risk of myocardial infarction, stroke and cardiovascular death associated with inhaled antimuscarinic drugs (ipratropium or tiotropium). A trial published after this metaanalysis, the Uplift study, including 5993 COPD patients followed for 4 years, showed no statistically significant difference in the frequency of cardiovascular death, myocardial infarction or stroke in the inhaled tiotropium group compared with the placebo group. However, these results are not sufficient to dispel the strong suspicion of an increased risk of cardiovascular adverse effects. In practice, the use of an inhaled antimuscarinic drug should be discussed on a case by case basis, weighing the only modest benefits against the worrisome risk of cardiovascular events.