Inhaled Anticholinergics Increase Risk for Cardiac Events

A new study has shown that use of inhaled anticholinergics, the most commonly prescribed once-a-day treatment for chronic obstructive pulmonary disease (COPD), increases the risk of cardiovascular death, heart attack, or stroke by more than 50%.

Researcher at Wake Forest University School of Medicine (Winston-Salem, NC, USA) and the University of East Anglia (Norwich, UK) conducted a meta-analysis of 17 double blind, randomized trials involving a total of 14,783 patients with COPD. Participants received treatment with inhaled anticholinergics, another form of active therapy, or a placebo inhaler. The primary outcome was a composite of cardiovascular death, myocardial infarct (MI), or stroke. The secondary outcome was all-cause mortality. Follow-up duration ranged from six weeks to five years.

The results showed that cardiovascular death, MI, or stroke occurred in 135 of 7472 patients (1.8%) receiving inhaled anticholinergics for longer than one month, and 86 of 7311 patients (1.2%) receiving control therapy. Among individual components of the primary endpoint, inhaled anticholinergics significantly increased the risk of MI and cardiovascular death without a statistically significant increase in the risk of stroke. All-cause mortality was reported in 149 of the patients treated with inhaled anticholinergics (2.0%) and 115 of the control patients (1.6%). A sensitivity analysis restricted to five long-term trials (over six months) confirmed the significantly increased risk of cardiovascular death, MI, or stroke (2.9% of patients treated with anticholinergics versus 1.8% of the control patients). The study was published in the September 24, 2008, issue of The Journal of the American Medical Association (JAMA).

"Patients with COPD who use these inhalers are at a high risk of excess serious cardiovascular events due to their use,” said co-author Sonal Singh, M.D., M.P.H., an assistant professor of internal medicine at Wake Forest. "These findings, especially the magnitude of the risk, and the consistency of the risk for heart attack, stroke, and cardiac death, urge caution in the widespread use of these agents. Patients and doctors should decide whether these serious long-term cardiovascular risks outweigh their symptomatic benefits.”

Inhaled anticholinergics are a class of drugs that relax the airways and prevent them from getting narrower, making it easier to breathe. They also protect the airways from bronchospasms that can suddenly cause the airway to constrict. The two most commonly used inhalers from the anticholinergic class are tiotropium bromide and ipratropium bromide.

Related Links:
Wake Forest University School of Medicine
University of East Anglia