O1.1.2 Short-acting muscarinic antagonist (SAMA)

Bronchodilators such as ipratropium, tiotropium, glycopyrronium, aclidinium and umeclidinium are not ‘anticholinergics’ since they are unable to antagonize the effects of acetylcholine on nicotinic receptors. They only block the muscarinic effects of acetylcholine. The word ‘anticholinergic’ suffers from pharmacodynamic approximation and should be replaced by ‘antimuscarinic’ (if we consider the involved receptor) or ‘atropinic’ (in relation to the pharmacodynamics effects of this drug class) (Montastruc 2010).

The duration of action of short-acting muscarinic antagonists (formerly known as anticholinergics) is greater than short-acting beta2-agonists. A systematic review of randomised controlled trials comparing ipratropium bromide alone, or in combination with short-acting beta2-agonists, against  short-acting beta2-agonists alone found significant benefits for regimens containing ipratropium bromide (Appleton 2006a). Ipratropium bromide improved spirometry over short-acting beta2-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 corticosteroids for participants receiving ipratropium bromide,with 15 (95% CI 12 – 28) people requiring treatment with ipratropium bromide to prevent one receiving additional oral corticosteroids.

However, some studies have found that ipratropium bromide is associated with an increased risk of adverse cardiovascular effects (Lee 2008, Singh 2008, Ogale 2010). A nested case-control study (Lee 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 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].

A Cochrane meta-analysis comparing treatment with tiotropium [HandiHaler or Respimat] with ipratropium bromide (via MDI) for patients with stable COPD found that tiotropium treatment, was associated with improved lung function, fewer hospital admissions (including those for exacerbations of COPD), fewer exacerbations of COPD and improved quality of life. There were both fewer serious adverse events and disease specific events in the tiotropium group, but no significant difference in deaths with ipratropium bromide when compared to tiotropium. Thus, tiotropium appears to be a reasonable choice (instead of ipratropium bromide) for patients with stable COPD (Cheyne 2015).