Anticholinergics linked with CVD in COPD patients
Patients with COPD who are prescribed ipratropium or tiotropium are at an increased risk of cardiovascular events.
A systematic review identified randomised, controlled trials of inhaled anticholinergics used for the treatment of COPD in which participants had had at least 30 days of treatment and reported on cardiovascular events. Seventeen trials, with a total of 14,783 patients, were included. The duration of follow-up ranged from six weeks to five years.
The primary endpoint of the analysis was a composite of cardiovascular death, MI, or stroke.
The secondary endpoint was all-cause mortality.
The primary endpoint occurred in 135 patients (1.8%) prescribed an anticholinergic and 86 (1.2%) of controls, with a relative risk of 1.58 (95% CI 1.21-2.06, P= <0.001). The secondary endpoint did not differ significantly between the two groups, with an all-cause mortality rate of 2% in patients who received anticholinergic therapy and 1.6% in those assigned to a control group (RR 1.26, 95% CI 0.99-1.61, P= 0.06).
An analysis of the five trials that were followed up for longer than six months confirmed that the significantly increased risk of cardiovascular death, MI, or stroke remained (2.9% for patients assigned to anticholinergic therapy compared with 1.8% for those in a control group, RR 1.73, 95% CI 1.27-2.36, P= <0.001). When the anticholinergics were analysed separately, the relative risk of cardiovascular disease was 1.57 (95% CI 1.08-2.28, P= 0.02) with ipratropium and 2.12 (95% CI 1.22-3.67, P= 0.008) with tiotropium.
Patients with COPD are often at increased risk of cardiovascular disease because of a history of smoking. This review certainly provides food for thought and, if its findings are confirmed, a careful appraisal of risks and benefits will be required before initiating long-term anticholinergic therapy in patients with COPD, particularly if they have concomitant cardiovascular disease.
Singh S, Loke YK, Furberg CD et al. Inhaled Anticholinergics and Risk of Major Adverse Cardiovascular Events in Patients With Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis. JAMA 2008;300:1439-50Reviewer
Dr Peter Savill
GPwSI Cardiology, Southampton