Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications
- 1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- 2Norwich Medical School, University of East Anglia, Norwich, UK
- 3College of Public Health, University of Arizona, Tucson, Arizona, USA
- 4Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
- Correspondence to Dr Sonal Singh, Department of Medicine, 624 N Broadway, St 680 B and Baltimore, MD, 21205-1901 USA;
Contributors SS drafted the manuscript, acquired the data, and carried out the statistical analysis. All authors analysed and interpreted the data and critically revised the manuscript for important intellectual content. SS takes responsibility for the integrity of the data and the accuracy of the report and is guarantor.
- Received 24 October 2011
- Accepted 7 June 2012
- Published Online First 4 July 2012
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.
- COPD epidemiology
- COPD pharmacology
- drug-induced lung disease
- drug reactions
- health economist
- clinical epidemiology
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.