Matthew B. Stanbrook, MD, PhD
In patients with chronic obstructive pulmonary disease (COPD), do inhaled anticholinergics increase risk for major cardiovascular events?
Studies selected compared an inhaled anticholinergic with placebo or active drugs in patients with COPD and reported serious cardiovascular adverse events. Outcomes were a composite cardiovascular endpoint (nonfatal myocardial infarction, nonfatal stroke [including transient ischemic attack], or cardiovascular death [including sudden death]), its components, and all-cause death.
MEDLINE (Mar 2008), Cochrane Database of Systematic Reviews, Web sites of the US Food and Drug Administration and European regulatory authorities, ClinicalTrials.gov, drug company product information sheets and clinical trials registers, reference lists, and Web of Science Citation Index were searched for English-language, published or unpublished, randomized controlled trials (RCTs) with > 30 days of follow-up. 17 RCTs (n = 13 645, mean age 49 to 68 y, 58 to 99% men) met the selection criteria. The anticholinergic was tiotropium in 12 RCTs and ipratropium in 5 RCTs. The comparator was placebo in 9 RCTs, salmeterol in 5 RCTs, salmeterol plus fluticasone in 2 RCTs, and albuterol in 1 RCT. All trials were double-blind, and 4 trials reported adequate allocation concealment. Duration of follow-up ranged from 6 to 26 weeks in 11 short-term trials and from 48 weeks to 5 years in 6 long-term trials.
Inhaled anticholinergics increased risk for the composite endpoint, myocardial infarction, and cardiovascular death, but not stroke or all-cause death (Table). Inhaled anticholinergics increased risk for the composite endpoint in the 6 long-term trials (n = 7222, relative risk [RR] 1.7, 95% CI 1.3 to 2.4) but not in the 11 short-term trials (n = 6423, RR 1.2, CI 0.69 to 2.2).
In patients with chronic obstructive pulmonary disease, long-term use of inhaled anticholinergics increases risk for major cardiovascular events.
Inhaled anticholinergics vs placebo or active drugs (control) in patients with chronic obstructive pulmonary disease†
†Abbreviations defined in Glossary. Weighted event rates, RRI, NNH, and CI calculated from data in article using a fixed-effect model.
‡Myocardial infarction, stroke, or cardiovascular death.
Stanbrook MB. Review: Inhaled anticholinergics increase risk for major cardiovascular events in chronic obstructive pulmonary disease. Ann Intern Med. ;150:JC1–6. doi: 10.7326/0003-4819-150-2-200901200-02006
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Published: Ann Intern Med. 2009;150(2):JC1-6.
Chronic Obstructive Airway Disease, Pulmonary/Critical Care.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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