New Research Results

New Use of LABAs, LAAs Boosts Cardiovascular Risk in Older Patients With COPD

May 29, 2013 03:00 pm News Staff

According to a Canadian study(archinte.jamanetwork.com) published May 20 in JAMA Internal Medicine, older patients with chronic obstructive pulmonary disease (COPD) who are new users of long-acting beta agonists (LABAs) and long-acting anticholinergics (LAAs) are at an increased risk of cardiovascular events.

Although the LABAs salmeterol xinafoate and formoterol fumarate and the LAA tiotropium bromide monohydrate generally are considered effective treatments for COPD, the cardiovascular safety of the medications remains a matter of debate.

"We conducted an observational, population-based study to compare the cardiovascular risk associated with LAA and LABA use in older individuals with COPD and found increased risks of hospitalization and emergency department visits for cardiovascular disease in new users of both medications but no evidence of differing risk between medications," said the study authors. "This lack of a difference was independent of sex, preexisting cardiovascular disease and COPD severity."

Story Highlights
  • According to a May 20 study in JAMA Internal Medicine, older patients with chronic obstructive pulmonary disease who initiate use of long-acting beta agonists (LABAs) and long-acting anticholinergics (LAAs) are at an increased risk of cardiovascular events.
  • Of the more than 190,000 eligible patients in the study, 28 percent were hospitalized or taken to the emergency department because of a cardiovascular event.
  • LABAs and LAAs were associated with similar risks of acute coronary syndrome, congestive heart failure and arrhythmia.

Specifically, the authors noted, of the more than 190,000 patients involved in the study, nearly 54,000 -- 28 percent -- had a hospitalization or an emergency department visit for a cardiovascular event.

"Compared with nonuse of either medication, LABA and LAA use were associated with an increased risk of acute coronary syndrome and heart failure but not cardiac arrhythmias or stroke," said the authors. In addition, "A protective effect for ischemic strokes was observed with new LAA but not new LABA use."

In an accompanying commentary(archinte.jamanetwork.com) on the study, pulmonologist and critical care specialist Prescott Woodruff, M.D., M.P.H., of the University of California, San Francisco, said that although no pharmacotherapy has proven effective in halting the progression of COPD, LABAs and LAAs are important mainstays of treatment because they improve lung function, reduce dyspnea, decrease the rate of exacerbations and enhance quality of life. Unfortunately, however, the safety concerns detailed in the study make prescribing and using the drugs a gray area, he said.

"The current observational study adds to our body of knowledge by providing information that is complementary to clinical trial data, and it addresses the real question facing providers: 'Which of the long-acting bronchodilators should I choose in the treatment of my patients?'" said Woodruff. "However, observational studies have an intrinsic vulnerability to hidden confounders.

"Because COPD is a systemic disease resulting from susceptibility factors that increase the risk for obstructive lung disease and for the cardiovascular complications of smoking, one hidden confounder could be these shared susceptibility factors."

According to Woodruff, two important questions remain unanswered:

  • What are the relative risks associated with use of Boehringer Ingelheim/Pfizer's dry-powder tiotropium inhaler (Spiriva HandiHaler) and Boehringer Ingelheim's tiotropium solution inhaler (Respimat Soft Mist Inhaler)?
  • What are the relative risks associated with use of an LABA alone versus an LABA-inhaled corticosteroid combination inhaler?

Woodruff also pointed out that the study authors' recommendation to closely monitor older patients with COPD who are using these medications lacks a firm definition of what that monitoring should look like.

"Monitoring, of course, is the responsibility of an informed treating physician," he noted. "The main contribution of this study is to highlight that responsibility."


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