Anticholinergics increase risk of cardiovascular death

Inhaled anticholinergics – such as ipratropium or tiotropium bromide – are commonly prescribed to patients with chronic obstructive pulmonary disease (COPD).  A previous analysis of 19 short-term placebo-controlled trials had suggested a possible increased risk of stroke with inhaled tiotropium, therefore Singh et al. performed a meta-analysis of 17 trials enrolling 14783 patients in order to ascertain the cardiovascular risks of inhaled anticholinergics.

Follow up duration ranged from 6 weeks to 5 years.  Cardiovascular death, myocardial infarction, or stroke occurred in 135 of 7472 patients (1.8%) receiving inhaled anticholinergics and 86 of 7311 patients (1.2%) receiving control therapy (relative risk, 1.58); p<0.001).  Specifically, anticholinergic therapy significantly increased the risk of myocardial infarction (relative risk, 1.53, p=.03) and cardiovascular death (relative risk, 1.80, p=.008) without a significant increase in the risk of stroke (relative risk, 1.46, p=.20).  All-cause mortality was reported in 149 of the patients taking anti-cholinergics (2.0%) and 115 of the control patients (1.6%, relative risk 1.26, p=.06), and a sensitivity analysis restricted to only the long-term trials confirmed the increased risk of cardiovascular death, myocardial infarction, or stroke (2.9% vs. 1.8%; p<0.001).

Most of the excess risk was found to come when anticholinergics were taken for at least six months.  Although the risk of cardiovascular death increased by some 80%, anticholinergics can cause a significant improvement in symptoms of breathlessness in COPD patients.  As a result, any risk associated with their use may still remain acceptable to some patients.  Furhter information on this risk should be obtained from the upcoming UPLIFT (Understanding Potential Long-Term Impacts on Function with Tiotropium) study.

  • Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease. A systematic review and meta-analysis. JAMA 2008; 300:1439-1450.

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