CYP2C19 Genotype-Guided Antiplatelet Therapy in ST-Segment Elevation Myocardial Infarction Patients – Patient Outcome After Primary PCI - POPular Genetics

Contribution To Literature:

The POPular Genetics trial showed that a genotype-guided strategy was noninferior for net outcomes (ischemia/bleeding) and superior for bleeding (mostly minor bleeding).

Description:

The goal of the trial was to evaluate a genotype-guided strategy for selection of oral P2Y12 inhibitor compared with standard therapy with ticagrelor or prasugrel among patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).

Study Design

  • Randomized
  • Parallel
  • Open-label

Patients undergoing primary PCI for STEMI were randomized to a genotype-guided strategy for selection of oral P2Y12 inhibitor (n = 1,242) versus standard therapy with ticagrelor or prasugrel (n = 1,246).

In the genotype-guided group, detection of CYP2C19*2 or CYP2C19*3 resulted in the use of ticagrelor or prasugrel. Otherwise patients received clopidogrel.

  • Total number of enrollees: 2,488
  • Duration of follow-up: 12 months
  • Mean patient age: 62 years
  • Percentage female: 26%
  • Percentage with diabetes: 12%

Inclusion criteria:

  • Patients ≥21 years of age undergoing primary PCI for STEMI

Principal Findings:

The primary net outcome of death, MI, stroke, stent thrombosis, or major bleeding (PLATO criteria) at 12 months occurred in 5.1% of the genotype-guided group compared with 5.9% of the standard care group (p for noninferiority < 0.001).

Major or minor bleeding (PLATO criteria) at 12 months occurred in 9.8% of the genotype-guided group compared with 12.5% of the standard care group (p = 0.04).

Secondary outcomes:

  • Cardiovascular death, MI, stroke, or stent thrombosis at 12 months: 2.7% of the genotype-guided group compared with 3.3% of the standard care group (p = not significant)
  • Major bleeding at 12 months (PLATO criteria): 2.3% of the genotype-guided group compared with 2.3% of the standard care group (p = not significant)
  • Major bleeding at 12 months (BARC type 3-5 criteria): 2.5% of the genotype-guided group compared with 2.3% of the standard care group (p = not significant)
  • Major bleeding at 12 months (TIMI criteria): 1.2% of the genotype-guided group compared with 1.3% of the standard care group (p = not significant)

Interpretation:

Among patients with STEMI undergoing primary PCI, a genotype-guided strategy vs. standard of care was associated with noninferiority with respect to a net composite outcome. A genotype-guided strategy was associated with superiority with respect to major or minor bleeding. However, a genotype-guided strategy was not associated with a reduction in major bleeding as defined by three criteria.

References:

Claassens DM, Vos GJ, Bergmeyer TO, et al. A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI (POPular Genetics). N Engl J Med 2019;Sep 3:[Epub ahead of print].

Presented by Dr. Danny Claassens at the European Society of Cardiology Congress, Paris, France, September 3, 2019.

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Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Anticoagulation Management and ACS, Interventions and ACS

Keywords: ESC Congress, ESC 19, Acute Coronary Syndrome, Adenosine, Anticoagulants, Genotype, Genotyping Techniques, Hemorrhage, Myocardial Infarction, Percutaneous Coronary Intervention, Standard of Care, Stents, Stroke, Thrombosis


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