Inhaled anticholinergic agents can lead to adverse cardiac events and death. Image Source: Heart Valve Surgery

The use of inhaled anticholinergic agents by patients with chronic obstructive pulmonary disease (COPD) is associated with a significantly increased risk of heart attack, stroke or cardiovascular death, according to a meta-analysis of randomized trials published in the Sept. 24 issue of Journal American Medical Association.

COPD is the fourth U.S. leading cause of chronic illness and death, and is projected to rank fifth in 2020 in burden of disease worldwide. Inhaled anticholinergic agents, including ipratropium bromide or tiotropium bromide, are widely used in patients with COPD, but their effect on the risk of cardiovascular outcomes is unknown, according to background information in the study.

Inhaled tiotropium is the most widely prescribed medication for COPD, with more than eight million patients worldwide having used it since its approval in 2002.

Sonal Singh, MD, of Wake Forest University School of Medicine in Winston-Salem, N.C., and colleagues conducted a meta-analysis to determine cardiovascular risks (MI, stroke, and cardiovascular death) associated with the long-term use of inhaled anticholinergics.

After identifying and a detailed screening of 103 articles, the researchers analyzed 17 randomized trials, which enrolled 14,783 patients with a follow-up duration ranging from six weeks to fix years.

According to investigators, the analysis indicated that inhaled anticholinergics significantly increased the risk, by 58 percent, of cardiovascular death, MI or stroke (1.8 percent vs. 1.2 percent for controls). Among individual components of the primary outcome, inhaled anticholinergics significantly increased the risk of MI by 53 percent (1.2 percent vs. 0.8 percent for controls) and also significantly increased (by 80 percent) the risk of cardiovascular death (0.9 percent vs. 0.5 percent for controls), the authors wrote.

All-cause death was reported in 149 of the patients treated with inhaled anticholinergics (2.0 percent) and 115 of the control patients (1.6 percent), according to Singh and colleagues. A sensitivity analysis restricted to five long-term trials (greater than six months) confirmed the significantly increased risk (73 percent) of cardiovascular death, MI or stroke (2.9 percent of patients treated with anticholinergics vs. 1.8 percent of the control patients).

“Chronic obstructive pulmonary disease is an independent risk factor for cardiovascular hospitalization and cardiovascular death.

Cardiovascular death is a more frequent cause of death in patients with COPD than respiratory causes, with the proportion of cardiovascular deaths increasing with the severity of the disease,” the authors wrote.

“Clinicians need to closely monitor patients with COPD who are taking long-term anticholinergics for the development of cardiovascular events. Clinicians and patients should carefully consider these potential long-term cardiovascular risks of inhaled anticholinergics in the treatment of COPD, and decide whether these risks are an acceptable trade-off in return for their symptomatic benefits,” Singh and colleagues concluded.