Aclidinium does not confer cardiovascular risk: ASCENT COPD

  • Wise RA & al.
  • JAMA
  • 7 May 2019

  • International Clinical Digest
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Takeaway

  • For COPD, the long-acting muscarinic antagonist (LAMA) aclidinium bromide (AB; Tudorza Pressair, AstraZeneca) does not appear to confer cardiovascular risk vs placebo.
  • It reduced moderate-to-severe exacerbations.

Why this matters

  • One-third of COPD deaths are cardiovascular.
  • LAMA cardiovascular safety is debated; observational but not trial evidence suggests LAMAs increase risk in patients with COPD.
  • This trial enrolled higher-risk patients; excluding them may have skewed previous trials.
  • Aclidinium’s reduction of exacerbations has not been assessed past 6 months.

Study design

  • Multicenter, randomized, placebo-controlled, double-blind ASCENT COPD study (n=3589).
  • Adults with COPD and higher cardiovascular risk were randomly assigned to AB vs placebo for ≤3 years.
  • Outcome: major adverse cardiac event (MACE) within 3 years; annual moderate-to-severe COPD exacerbation rate during first year of treatment.
  • Funding: Forest Laboratories; AstraZeneca; Circassia.

Key results

  • With AB vs placebo:
    • MACE: 69 (3.9%) vs 76 (4.2%);
      • HR, 0.89 did not cross noninferiority margin of 1.8.
    • Exacerbations: 0.44 vs 0.57;
      • Rate ratio, 0.78 (2-sided 95% CI, 0.68-0.89; P<.001>
    • All-cause mortality (exploratory): no significant difference.
  • With AB, fewer exacerbations requiring hospitalization.
  • Similar between-group adverse event rates.

Limitations

  • Underpowered to detect causes of death; increased cardiovascular mortality is possible.