Tudorza Reduces COPD Flare-ups Without Increasing Risk of Cardiovascular Complications or Death, Phase 4 Trial Shows

Tudorza (aclidinium bromide) reduces flare-ups in patients with moderate to severe chronic obstructive pulmonary disease (COPD) without increasing the risk of cardiovascular complications such as heart attack and stroke, or death, data from a Phase 4 trial show.

The findings were discussed by Robert Wise, MD, from Johns Hopkins University, in a presentation titled “Aclidinium bromide treatment stratified by exacerbation history: effects on exacerbations and major cardiovascular events in patients with COPD and high cardiovascular risk (ASCENT-COPD)” at the CHEST Annual Meeting, held this week in New Orleans.

Tudorza, developed by AstraZeneca and marketed by Circassia Pharmaceuticals in the U.S., is a bronchodilator used as a form of long-term treatment for people with COPD. Its active ingredient, aclidinium bromide, is a long-acting muscarinic antagonist that triggers relaxation of smooth muscles surrounding the airways, making it easier for patients to breathe.

Despite its positive effects in reducing the number of COPD flare-ups, there has been some controversy in the medical community about the safety of Tudorza among patients who are at risk of developing cardiovascular problems, a common condition among those with COPD.

Wise presented the findings from a subgroup analysis of ASCENT-COPD (NCT01966107), a randomized, double-blind, placebo-controlled, Phase 4 trial designed to assess the safety and effectiveness of Tudorza in COPD patients who also had cardiovascular problems or were at a high risk of developing them.

ASCENT enrolled 3,635 patients with moderate to very severe COPD who were treated with 400 micrograms of Tudorza or a placebo, twice a day via the Pressair inhaler, for up to three years.

The subgroup analysis, which included data from 3,589 patients, focused on examining the safety of Tudorza and its long-term effects on several cardiovascular events, including death and non-fatal heart attacks and strokes, among patients with and without COPD flare-ups (disease exacerbations) in the previous year.

More than half of the patients in either group (59.6% in the Tudorza group and 60.5% of the placebo group) had at least one COPD exacerbation in the previous year.

Results showed that, compared to the placebo, Tudorza significantly reduced the frequency of COPD exacerbations in all patients, regardless of whether they had an episode of disease exacerbation in the previous year.

In addition, the medication did not increase the risk of cardiovascular complications or all-cause mortality compared with the placebo in any of the participants.

According to Wise, these findings address two issues that have been surrounding the use of Tudorza as a treatment for COPD.

“First, there has been some controversy over the cardiovascular safety of aclidinium, which this study shows not to be a problem. Second, although aclidinium has been shown to be a good bronchodilator, the overall study indicates that it is also effective in reducing exacerbations, which is a pivotal finding,” Wise said in a news release.

“Most studies of exacerbations include only patients who have had an exacerbation in the preceding year whereas ASCENT included patients both with and without exacerbations. Therefore, the finding that there was a similar risk reduction in those with and without exacerbations is an important and novel finding and perhaps surprising to some,” Wise added.

Victor Test, MD, co-chair of the CHEST Scientific Program Committee and professor at Texas Tech University Health Sciences Center, shared a similar opinion: “This study addresses two very important issues in therapy for COPD — the effect of a long-acting anticholinergic agent on exacerbations and risk of cardiovascular events. In the highest risk patients, aclidinium bromide was superior to placebo in reducing exacerbations but did not increase cardiovascular events in high-risk patients.”

Of note, Wise emphasized that the “prevention of exacerbations of COPD should be a treatment goal in COPD patients regardless of whether they have a history of recent exacerbations.”