No difference in cardiac risk between 2 bronchodilators

It’s a toss-up: In a comparison of their relative cardiovascular risk, neither of two long-acting bronchodilators for chronic obstructive pulmonary disease (COPD) appeared to be safer than the other.

Similar to other observational studies, the results published online May 20 in JAMA Internal Medicine on risks associated with long-acting beta-antagonists (LABAs) and anticholinergics (LAAs) contradicted findings from randomized clinical trials.

“Long-acting anticholinergics are believed to suppress parasympathetic control, whereas LABAs are believed to stimulate sympathetic control, both causing an increased risk of tachyarrhythmias, myocardial ischemia, stroke, and death,” wrote Andrea Gershon, MD, of the Institute of Clinical Evaluative Sciences in Toronto, and colleagues. Both are effective treatments for COPD; the question for physicians and patients may come down to which is safer.

To clarify that issue, Gershon et al conducted a population-based, case-controlled retrospective study using healthcare databases in Ontario, including the Ontario COPD database. They identified all patients who were 66 years old or older who received a prescription for an LABA or LAA between 2003 and 2009. The primary outcome was a hospital or emergency room visit for a cardiovascular event, which encompassed an acute coronary syndrome, heart failure, ischemic stroke or cardiac arrhythmia.

Of the 191,005 patients identified, 28 percent had a hospital or emergency room visit for a cardiovascular event. Nearly half of that group was matched to a control. They found that new users were more likely to have a hospital or emergency room visit for a cardiovascular event compared with patients not taking either an LABA or an LAA. But results showed no difference in risk between the two medications. Risk did not differ by sex, pre-existing cardiovascular disease or COPD severity.

Randomized clinical trials have shown clinical benefits of long-acting bronchodilators for treating moderate to severe COPD. But unlike clinical trial data, some observational studies and meta-analyses point to possible cardiovascular risks.  

“Our study also found significantly increased cardiovascular risk associated with the new use of LABAs and the new use of LAAs relative to nonuse of either drug,” they wrote. Their results also ran counter to clinical trial data that found no increased risk with either medication.

Gershon et al listed the differences between their population-based analyses and clinical trials. Those included a healthier patient population than in randomized clinical trials, which were underpowered to detect adverse events and were not designed to capture outcomes after follow-up. 

In an accompanying commentary, Prescott G. Woodruff, MD, MPH, of the Cardiovascular Research Institute at the University of California, San Francisco, underscored the value of a study based on real-world experiences but also cautioned about the possibility of confounding. The study did not further physicians’ understanding of the relative risk of the two medications nor did it distinguish between LABAs and a LABA-inhaled corticosteroid combination, he proposed.

“[A]lthough the authors recommend that ‘subjects should be monitored closely,’ a firm recommendation on what that monitoring should be cannot be made,” Woodruff wrote. “Monitoring, of course, is the responsibility of an informed treating physician. The main contribution of this study is to highlight that responsibility.”