O1.1.2 Short-acting anticholinergics

The duration of action of short-acting anticholinergics is greater than short-acting beta-agonists. A systematic review of randomised controlled trials comparing ipratropium bromide alone, or in combination with short-acting beta-agonists, against  short-acting beta-agonists alone found significant benefits for regimens containing ipratropium bromide.(Appleton et al., 2006a) Ipratropium bromide improved spirometry over short-acting beta-agonists alone, weighted mean difference = 30mls (95% CI 0 to 60) for FEV₁ and 70mls (95% CI 10 to 140) for FVC. Ipratropium bromide improved quality of life, with a statistically significant improvement in all domains of the Chronic Respiratory Disease Questionnaire. These benefits occurred with fewer minor adverse drug effects, Number Needed to Harm (NNH) = 32 (95% CI 20 to 316). There was a lesser need to add or increase the dose of oral glucocorticoids for participants receiving ipratropium bromide,with 15 (95% CI 12 – 28) people requiring treatment with ipratropium bromide to prevent one receiving additional oral glucocorticoids.

However, recent studies have found that ipratropium bromide is associated with an increased risk of adverse cardiovascular effects.(Lee et al., 2008, Singh et al., 2008, Ogale et al., 2010) A nested case-control study (Lee et al., 2008) [evidence level III-2] found an increased risk of cardiovascular death associated with the prescription of ipratropium, OR 1.34 (95% CI 1.22 to 1.47).  A meta-analysis of randomised controlled trials (Singh et al., 2008) found an increased risk for a combined cardiovascular endpoint of cardiovascular death, myocardial infarction and stroke, estimated NNH for cardiovascular death 40 (95% CI 18 to 185) per year.   The consistent finding across these studies suggests the cardiovascular adverse effects are likely to be real [evidence level I].