LAMAs Are Safe Irrespective of Cardiovascular Risk in COPD

Pam Harrison

October 10, 2018

SAN ANTONIO — Long-acting antimuscarinic antagonists (LAMAs) do not increase the risk for cardiovascular events in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), a post hoc analysis of the ASCENT study (NCT01966107) indicates.

"There has been more than a decade of controversy in the literature as to whether this class of agents is associated with an increased risk of CV events happening," said Ken Chapman, MD, from the Krembil Research Institute at the University of Toronto.

"We followed these patients for a period of up to 3 years, and there was no signal [of excess CV events] whatsoever in patients on LAMA, compared with placebo controls," he reported here at CHEST 2018.

"This is very reassuring," Chapman told Medscape Medical News. "LAMAs should be used if patients have an indication for their use, and that certainly would apply to the vast majority of patients with COPD."

Unlike other studies in the COPD field, ASCENT was done with patients at risk for cardiovascular disease, who are often excluded from phase 3 and phase 4 trials of COPD.

"Patients had moderate, severe, or very severe COPD, and they had increased CV risk, based on either a history of having a CV event or certain prespecified CV risk factors," Chapman explained.

The 3589 patients were randomized to receive either the long-acting antimuscarinic agent aclidinium 400 ug or placebo twice daily for 36 months.

For this particular subset analysis, patients were stratified into two groups on the basis of cardiovascular status. Roughly half the patients had had a previous cardiovascular event, and the other half had at least two cardiovascular risk factors, such dyslipidemia, hypertension, or low kidney function.

"This was also a very heavy population," Chapman reported. Mean body mass index was almost 30 kg/m², and 42% of patients were considered obese, with a BMI of at least 30 kg/m².

Table 1. Major Acute Cardiac Event During the Study Period
Cardiovascular Status Aclidinium Group, % Placebo Group, %
Previous cardiovascular event 5.5 6.2
At least 2 risk factors 2.4 2.4

For those with a previous cardiovascular event, the hazard ratio for time to the first major acute cardiac event was 0.86; for those with at least two risk factors, it was 0.99. Both hazard ratios were below the noninferiority margin of 1.8.

"It doesn't matter if your patients have had an event or are only at risk for an event, LAMA use does not confer any increased risk of subsequent CV events or MACE," Chapman said.

For patients with a previous cardiovascular event, the relative risk for a COPD exacerbation was 24% lower in the aclidinium group than in the placebo group (P = .004) during the first year of the trial. For patients with at least two risk factors, the relative risk was 20% lower (P = .0246).

Table 2. Hazard Ratio for COPD Exacerbation During Year 1
Cardiovascular Status Aclidinium Group, % Placebo Group, %
Previous cardiovascular event 0.48 0.63
At least 2 risk factors 0.42 0.52

About a decade ago, some people thought that long-acting antimuscarinic agents were associated with a very high level of cardiovascular risk, and there was a lot of publicity about this, said Brian Carlin, MD, from the University of Pittsburgh Medical Center in Pittsburgh.

I think these are safe drugs to use and if you need to use one, you should.

"But in this study, aclidinium was not inferior to placebo in terms of time to the first major adverse cardiac event, so I think these are safe drugs to use. If you need to use one, you should," Carlin told Medscape Medical News.

However, he added, he would likely keep a close watch on COPD patients with a history of cardiovascular events, just to be on the safe side.

Chapman reports multiple financial relationships with industry, including Boehringer Ingelheim, GlaxoSmithKline, Grifols, Sanofi, Genzyme, Novartis, Sanofi, and AstraZeneca. Carlin reports having served on advisory boards for AstraZeneca, Carlin reports having served on advisory boards for AstraZeneca, GlaxoSmithKline, and Sanovion.

CHEST 2018: American College of Chest Physicians Annual Meeting: Abstract 15940. Presented October 8, 2018.

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