Genotype-guided oral P2Y12 inhibition does not best clopidogrel post-PCI

  • Pereira NL & al.
  • JAMA
  • 25 Aug 2020

  • curated by Emily Willingham, PhD
  • Clinical Essentials
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Takeaway

  • For patients with acute coronary syndrome (ACS) and stable coronary artery disease (CAD), post-percutaneous coronary intervention (PCI) CYP2C19 genotype-guided oral P2Y12 inhibitors do not best clopidogrel at 1 year for ischemic event reduction.

Why this matters

  • Editorial: this “largest randomized study to date” may not have achieved statistical significance for its primary endpoint but does “provide many encouraging, hypothesis-generating findings.”

Key results

  • For the composite primary endpoint (cardiovascular death, myocardial infarction, stroke, stent thrombosis, severe myocardial ischemia) at 12 months, the genotype-guided (4.0%) vs clopidogrel (5.9%) groups did not differ (HR, 0.66; 95% CI, 0.43-1.02).
  • They also did not differ for any of 11 prespecified endpoints.
  • They also did not differ for the primary safety endpoint (major/minor bleeding; P=.58).
  • Similar results in sensitivity analyses.

Study design

  • Open-label randomized clinical trial, 40 centers in the United States, Canada, South Korea, and Mexico, May 2013-October 2018.
  • Of 5302 patients, 2650 received clopidogrel without initial genetic testing and 2652 received genotype-guided therapy (clopidogrel without the CYP2C19 allele or ticagrelor/prasugrel with it).
  • The 2650 clopidogrel participants were genotyped at 12 months.
  • Analysis was done on final cohort of 1849 patients with the CYP2C19 allele (903 genotype-guided, 946 clopidogrel).
  • Funding: NIH.

Limitations

  • Underpowered to detect an effect size
  • Provision of genotype-guided therapy was predicated on insurance coverage.