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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 14 783 patients 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 treatment (relative risk 1.58; p<0.001). Specifically, anticholinergic therapy significantly increased the risk of myocardial infarction (relative risk 1.53, p = 0.03) and cardiovascular death (relative risk 1.80, p = 0.008) without a significant increase in the risk of stroke (relative risk 1.46, p = 0.20). All-cause mortality was reported in 149 of the patients taking anticholinergics (2.0%) and 115 of the control patients (1.6%, relative risk 1.26, p = 0.06), 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 6 months. Although the risk of cardiovascular death increased by some 80%, anticholinergics can significantly improve symptoms of breathlessness in patients with COPD. As a result, any risk associated with their use may still remain acceptable to some patients. Further 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 …
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