Effect of Aclidinium Bromide on Major Cardiovascular Events and Exacerbations in High-Risk Patients With Chronic Obstructive Pulmonary Disease - ASCENT-COPD

May 08, 2019
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Forest Laboratories and AstraZeneca
Date Published:
05/07/2019
Date Updated:
05/08/2019
Original Posted Date:
05/08/2019
References

Contribution To Literature:

The ASCENT-COPD trial showed that aclidinium bromide versus placebo was noninferior regarding risk of CV events and superior at preventing COPD exacerbations.


Description:

The goal of the trial was to evaluate aclidinium bromide compared with placebo among patients with chronic obstructive pulmonary disease (COPD) and established cardiovascular disease (CVD) or risk factors.


Study Design

  • Randomized
  • Parallel
  • Blinded

Patients who met selection criteria were randomized to aclidinium bromide 400 μg twice daily (n = 1,812) versus placebo (n = 1,818) by dry-power inhaler.

  • Total number of enrollees: 3,630
  • Duration of follow-up: 3 years
  • Mean patient age: 67 years
  • Percentage female: 41%

Inclusion criteria:

  • Age ≥40 years
  • Moderate to severe COPD
  • Established CVD (stroke/transient ischemic attack, carotid stenosis, myocardial infarction, angina, coronary revascularization, or peripheral vascular disease) or,
  • At least 2 risk factors (≥65 years for men or ≥70 years for women, waist circumference ≥40 inches for men or ≥38 inches for women, estimated glomerular filtration rate <60 cc/min and microalbuminuria, dyslipidemia, diabetes, or hypertension)

Exclusion criteria:

  • Using triple therapy; inhaled corticosteroids, long-acting muscarinic antagonist, and long-acting beta-2 agonist
  • Unstable or life-threatening COPD or CVD
  • Lung disease other than COPD
  • Planned lung transplantation or lung surgery
  • Malignancy within the last 5 years

Principal Findings:

The primary safety outcome, major adverse CV event (CV death, myocardial infarction, or stroke), occurred in 3.9% of the aclidinium group compared with 4.2% of the placebo group (p for noninferiority < 0.05).

The primary efficacy outcome, annual rate of COPD exacerbation during the first year, was 0.44 in the aclidinium group compared with 0.57 in the placebo group (p < 0.001). Efficacy was observed in all subgroups, except those with forced expiratory volume in 1 second (FEV1) >50% of predicted (p for interaction = 0.01).

Secondary outcomes:

  • CV mortality: 1.5% for aclidinium versus 1.1% for placebo (p = not significant)
  • Annual rate of hospitalization due to COPD exacerbation: 0.07 for aclidinium versus 0.1 for placebo (p < 0.006)

Interpretation:

Among patients with moderate to severe COPD and established CVD or risk for CVD, aclidinium bromide versus placebo was noninferior regarding risk of CV events and superior regarding risk of COPD exacerbation. The results seem to apply to those with severe COPD (i.e., FEV1 <50% of predicted).

References:

Wise RA, Chapman KR, Scirica BM, et al. Effect of Aclidinium Bromide on Major Cardiovascular Events and Exacerbations in High-Risk Patients With Chronic Obstructive Pulmonary Disease: The ASCENT-COPD Randomized Clinical Trial. JAMA 2019;321:1693-1701.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and SIHD, Interventions and Vascular Medicine, Hypertension

Keywords: Angina Pectoris, Carotid Stenosis, Diabetes Mellitus, Dyslipidemias, Forced Expiratory Volume, Glomerular Filtration Rate, Hypertension, Ischemic Attack, Transient, Muscarinic Antagonists, Myocardial Infarction, Myocardial Revascularization, Peripheral Vascular Diseases, Primary Prevention, Pulmonary Disease, Chronic Obstructive, Risk Factors, Stroke, Vascular Diseases


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