Genotype-guided antiplatelet therapy in ACS

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

  • curated by Jenny Blair, MD
  • Clinical Essentials
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.


  • 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>


  • 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.

Please confirm your acceptance

To gain full access to GPnotebook please confirm:

By submitting here you confirm that you have accepted Terms of Use and Privacy Policy of GPnotebook.