Genotype-guided antiplatelet therapy in ACS

  • Notarangelo FM & al.
  • J Am Coll Cardiol
  • 24 Feb 2018

  • curated by Jenny Blair, MD
  • Clinical Essentials
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Takeaway

  • This prematurely terminated trial suggests that using pharmacogenomics to choose antiplatelet agent for patients with acute coronary syndrome (ACS) might improve outcomes.
  • Editorial raises concerns about type 1 error.

Why this matters

  • Among P2Y12 receptor antagonists (clopidogrel [Plavix], prasugrel [Effient], or ticagrelor [Brilinta]), clopidogrel has comparatively modest effect.
  • Patient response to clopidogrel varies based partly on genetics.

Study design

  • 12-month, randomized, prospective, multicenter clinical trial, PHARMCLO (Pharmacogenetics of Clopidogrel in Patients with Acute Coronary Syndromes).
  • 888 patients hospitalized with ACS randomly assigned to be prescribed P2Y12 receptor antagonist based on clinical variables alone vs clinical variables plus genotype.
  • Latter group underwent testing for clopidogrel responsiveness via bedside “disposable lab-on-chip” yielding results in 70 minutes.
  • Providers also prescribed based on clinical judgment.
  • Outcome: composite of cardiovascular death, ischemia, bleeding.
  • Funding: Emilia Romagna regional government, Italy.

Key results

  • Trial halted at 24.6% recruitment because of regulatory issues.
  • Across all patients, primary outcome reached in:
    • Pharmacogenomic arm: 71 patients (15.9%).
    • Standard-of-care arm: 114 (25.9%).
    • HR: 0.58 (95% CI, 0.43-0.78; P<.001>

Limitations

  • Standard-of-care arm undertreated and had more events.
  • Given early termination, results could be due to chance.
  • Genes’ relationship to clopidogrel-related outcomes “ambiguous” per editorial.

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