Inhaled Long-Acting Bronchodilators in COPD Flagged Again for CV Hazard

Shelley Wood

May 20, 2013

TORONTO, ON — Two commonly used drugs used in the treatment of chronic obstructive pulmonary disease (COPD) are associated with an increased risk of cardiovascular events, a new review concludes[1]. The study, published online May 21, 2013 in JAMA Internal Medicine, found that both inhaled long-acting beta-agonist (LABA) and long-acting anticholinergic drugs, when newly prescribed, were associated with a 31% increased risk of a CV event, when compared with nonprescription of these agents.

Dr Andrea Gershon (Institute for Clinical Sciences, Toronto, ON) and colleagues reviewed healthcare databases in Ontario identifying over 191 000 patients age >66 years treated for COPD over a five-year period. Of these, they noted, 53 532, or 28%, were hospitalized or admitted to an emergency department for ACS, heart failure, ischemic stroke, or cardiac arrhythmia. For the analysis, all COPD patients were matched with non-COPD patients.

Risk of events with both agents appeared to be highest within the first two or three weeks of starting the medication, and there were no differences between medications, Gershon et al write. When the individual cardiovascular end points were examined separately, the authors found that risk appeared to be increased for ACS and heart failure, but not for arrhythmias or stroke. In fact, a protective effect was seen for new long-acting anticholinergic agents for ischemic stroke, but not for new LABA prescription.

A link between long-acting bronchodilators and CV events was also seen in the POET-COPD randomized controlled trial, authors note, and with a previous, smaller analysis by the same group. But as an accompanying editorial by Dr Prescott G Woodruff (University of California, San Francisco) points out[2], other trials and analyses have been reassuring. Moreover, he notes, the drugs are considered "mainstays" of COPD management, because they improve lung function, dyspnea, rate of exacerbations, and quality of life. No other pharmacological approaches slow the progression of a disease that is the third most common cause of death in many countries worldwide.

Close Monitoring Warranted, but How?

"These results support the need for close monitoring of all patients with COPD who require long-acting bronchodilators, regardless of drug class," Gershon and colleagues state.

That conclusion, however, sits ill with Woodruff who points out that without a firm recommendation as to what exactly this monitoring should consist of, monitoring remains the same as it has always been--the responsibility of the treating physician.

"The main contribution of this article is to highlight that responsibility," Woodruff concludes.

Results of the ongoing TIOSPIR safety study may shed some light on the relative risks of different products that were not singled out in this study, Woodruff notes, for example, the Spiriva HandiHaler (Pfizer/Boehringer Ingelheim) and the Respimat Soft Mist Inhaler (Boehringer Ingelheim), which have different doses of tiotropium.

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