Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications

Thorax. 2013 Jan;68(1):114-6. doi: 10.1136/thoraxjnl-2011-201275. Epub 2012 Jul 4.

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.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review

MeSH terms

  • Administration, Inhalation
  • Aged
  • Aged, 80 and over
  • Arrhythmias, Cardiac / chemically induced*
  • Arrhythmias, Cardiac / mortality
  • Arrhythmias, Cardiac / physiopathology
  • Cause of Death*
  • Cholinergic Antagonists / adverse effects*
  • Cholinergic Antagonists / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Ipratropium / adverse effects
  • Ipratropium / therapeutic use
  • Male
  • Middle Aged
  • Myocardial Ischemia / chemically induced*
  • Myocardial Ischemia / mortality
  • Myocardial Ischemia / physiopathology
  • Prognosis
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / mortality
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Safety Management
  • Scopolamine Derivatives / adverse effects
  • Scopolamine Derivatives / therapeutic use
  • Survival Analysis
  • Tiotropium Bromide
  • Treatment Outcome

Substances

  • Cholinergic Antagonists
  • Scopolamine Derivatives
  • Ipratropium
  • Tiotropium Bromide