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

Sonal Singh, Yoon K. Loke, Paul Enright, Curt D. Furberg

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)114-116
Number of pages3
JournalThorax
Volume68
Issue number1
DOIs
StatePublished - Jan 2013

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Cholinergic Antagonists
Chronic Obstructive Pulmonary Disease
Myocardial Infarction
Mortality
Cardiac Arrhythmias
Ipratropium
Tiotropium Bromide
Tachycardia
Myocardial Ischemia
Meta-Analysis
Hospitalization
Ischemia
Randomized Controlled Trials
Heart Failure
Stroke
Placebos
Clinical Trials

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications. / Singh, Sonal; Loke, Yoon K.; Enright, Paul; Furberg, Curt D.

In: Thorax, Vol. 68, No. 1, 01.2013, p. 114-116.

Research output: Contribution to journalArticle

Singh, Sonal ; Loke, Yoon K. ; Enright, Paul ; Furberg, Curt D. / Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications. In: Thorax. 2013 ; Vol. 68, No. 1. pp. 114-116.
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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.",
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