Inhaled anticholinergics for the treatment of COPD is associated with an increased risk of cardiovascular events.

October,9 2008 By Michael W Tempelhof, MD [mailto:tempe004@mc.duke.edu]

Inhaled anticholinergics for the treatment of COPD is associated with an increased risk of cardiovascular events.

Utilization of inhaled anticholinergics (ipratropium or tiotropium) for greater then 30 days in patients with chronic obstructive pulmonary disease (COPD), is associated with a significant increased risk of cardiovascular events including cardiovascular death and myocardial infarction (MI).

COPD, a chronic, debilitating disease is the fourth leading cause of morbidity and mortality in the United States (U.S.). The complexity of COPD patients necessitates a poly-pharmacy treatment approach resulting in a large consumption of U.S. health care expenditures. The COPD Global Initiative for Lung Disease guidelines recommend inhaled anticholinergics as first-line agents for the long term therapy of COPD patients. In accordance with current guidelines and in appreciation of their favorable side effect profile, ipratropium and tiotropium have become the most widely prescribed agents for the maintenance therapy of COPD patients.

The cardiovascular safety of short-term anticholinergics therapy for COPD patients has been confirmed in previous analyses. However, the cardiovascular safety profile of long-term administration of anticholinergic therapy has not been confirmed. This meta-analysis investigated randomized controlled trials for an association of cardiovascular risk with long-term (greater then 30 days) administration of inhaled anticholinergic agents to patients with COPD.

The investigators assessed 17 trials, encompassing 14,783 patients (anticholinergics n= 7,472; controls n=7,311) with 12 trials using tiotropium, and 5 with ipratropium with a follow-up time of 6 weeks to 5 years. There was a significantly increased risk for the composite primary outcome of 58% (1.8% vs. 1.2%; RR,1.58; 95% CI, 1.21 to 2.06; P <0.001) in patients subjected to inhaled anticholinergics. Analysis of the separate primary outcomes demonstrated an increased risk of cardiovascular death of 80% (0.9% vs. 0.5%; RR, 1.80; [95% CI, 1.17 to 2.77]; P =0.008) and for MI of 53% (RR, 1.53; [95% CI, 1.05 to 2.23]; P = 0.03), but there was no significant increased risk for stroke (0.5% vs. 0.4%; RR, 1.46; [95% CI, 0.81 to 2.62]; P =0.20). The Number Needed to Harm (NNH) for cardiovascular death with anticholinergics was 40 per year and the NNH for MI was 174 per year.

Use of inhaled anticholinergics for more then 30 days is associated with a 80% increased risk for cardiovascular death and 53% increase risk for MI among COPD patients.

Source
http://jama.ama-assn.org/cgi/content/abstract/300/12/1439