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.

Risk of cardiovascular events after initiation of long-acting bronchodilators in patients with chronic obstructive lung disease: A population-based study

“…Salpeter et al, 19 in a meta-analysis of 33 placebo-controlled RCTs, demonstrated an increased risk of cardiovascular events with SABA and LABA in patients with COPD and asthma. Singh et al, 20,28 in a meta-analysis of 17 RCTs, showed an increased risk of a composite end point of cardiovascular death, myocardial infarction or stroke for ipratropium and tiotropium compared to placebo. However, reanalysis of Singh et al 29 in 2008 when UPLIFT trial data was added failed to show an increased risk.…”

Chronic Obstructive Pulmonary Disease and Cardiac Diseases. An Urgent Need for Integrated Care

“…Treatment of COPD in patients with concomitant AF should be the same as those without AF. Bronchodilators have been described as potential proarrhythmic agents (200,201), but available evidence suggests an overall acceptable safety profile for using LABA, LAMA, and ICS (202,203). For example, tiotropium does not increase the overall risk of cardiac arrhythmias (204), whereas a slightly higher incidence of AF has been reported in patients treated with glycopyrronium compared with placebo, despite an overall good safety profile (104).…”

Comparison of Beers criteria and EU(7) potentially inappropriate medications list for the potentially inappropriate medications in Indian elderly inpatients

“…26,27 However, they increase the risk of cardiovascular morbidity and mortality. 28,29 They require cautious use in patients having cardiac disorders. Amlodipine is well tolerated and effective antihypertensive.…”