title: Republished: pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications.
abstract: The majority of deaths in COPD are from cardiovascular causes. Several large randomized controlled trials demonstrate that inhaled anticholinergic agents ipratropium and tiotropium increase the risk of serious cardiovascular events, including cardiovascular mortality. Tiotropium Respimat is associated with a statistically significant increased risk of mortality (RR 1.52; 95% CI 1.06 to 2.16) and cardiovascular death (RR 2.05; 95% CI 1.06 to 3.99) compared with placebo in a meta-analysis of clinical trials. In the largest study, the subgroup of patients with COPD in the Respimat group with known rhythm and cardiac disorders at baseline had an especially high risk for cardiac death (RR 8.6; 95% CI 1.1 to 67.2). Although there was no significantly increased risk of mortality (HR 0.89; 95% CI 0.79 to 1.02) or myocardial infarction (MI) (RR 0.73; 95% CI 0.53 to 1.00) with tiotropium handihaler in the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, the reported excess of angina (RR 1.44; 95% CI 0.91 to 2.26), imbalance in strokes related to ischaemia and rates of supraventricular tachyarrhythmias are consistent with the pro-ischemic and pro-arrhythmic effects. The subjects at greatest risk of cardiovascular death, such as those with a recent history of MI, unstable or life-threatening cardiac arrhythmias or hospitalisation with heart failure, were excluded from the UPLIFT trial. The Prevention of Exacerbations with Tiotropium in COPD trial showed an excess of serious coronary ischaemic events of angina, myocardial ischaemia and MI with the tiotropium Handihaler compared with salmeterol. The authors urge caution in prescribing inhaled anticholinergics for patients with pre-existing arrhythmias or cardiac disorders.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Singh
authors.forename: Yoon K
authors.initials: YK
authors.lastname: Loke
authors.forename: Paul
authors.initials: P
authors.lastname: Enright
authors.forename: Curt D
authors.initials: CD
authors.lastname: Furberg
mesh_terms: D000280:Administration, Inhalation; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000009:adverse effects*; D020521:Stroke / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology; D000069447:Tiotropium Bromide
chemical_list: D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D009241:Ipratropium; D000069447:Tiotropium Bromide
keywords: COPD epidemiology; COPD pharmacology; clinical epidemiology; drug reactions; drug-induced lung disease; health economist; pneumonia