Key result
Homozygous PEAR1 rs2768759 minor allele carriers had a significantly increased risk of the primary combined endpoint of death, myocardial infarction, or ischemic stroke compared to major allele carriers (HR 3.16).
Why the study?
Are PEAR1 genetic variants associated with adverse cardiovascular outcomes in patients with ACS or stable CAD undergoing PCI on dual antiplatelet therapy?
Cohort (n=582)
Single-blind
No
Are PEAR1 genetic variants associated with adverse cardiovascular outcomes in patients with ACS or stable CAD undergoing PCI on dual antiplatelet therapy?
Hazard Ratio: 3.16 (95% CI 1.4–7.13)
p-value: p=0.006
Distinct genetic variants of PEAR1, particularly the homozygous rs2768759 minor allele, are associated with a significantly increased risk of death, MI, or ischemic stroke in high-risk patients undergoing PCI on dual antiplatelet therapy.
PEAR1 rs2768759 homozygosity signals higher ischemic risk on DAPT post-PCI; leaves open whether genotyping should guide therapy.
Introduction: Platelet endothelial aggregation receptor 1 (PEAR1) triggers platelet aggregation and is expressed in platelets and endothelial cells. Genome-wide association studies (GWAS) showed an association between platelet function and single-nucleotide polymorphisms (SNPs) in PEAR1. Methods: In 582 consecutive patients with stable coronary artery disease or acute coronary syndrome scheduled for PCI and treated with ASA and Clopidogrel, Prasugrel or Ticagrelor, single-nucleotide polymorphism analysis for rs12566888, rs2768759, rs41273215, rs3737224 and rs822442 was performed. During a follow-up period of 365 days after initial PCI, all patients were tracked for a primary endpoint, defined as a combined endpoint consisting of either time to death, myocardial infarction (MI) or ischemic stroke. All cause mortality, MI and ischemic stroke were defined as secondary endpoints. Results: Multivariable Cox model analysis for the primary endpoint revealed a significantly increased risk in homozygous PEAR1 rs2768759 minor allele carriers (hazard ratio, 3.16; 95% confidence interval, 1.4-7.13, p = 0.006). Moreover, PEAR1 rs12566888 minor allele carriers also showed an increased risk in all patients (hazard ratio, 1.69; 95% confidence interval, 0.87-3.27, p = 0.122), which was marginally significant in male patients (hazard ratio, 2.12; 95% confidence interval, 1.02-4.43, p = 0.045; n=425). Conclusions: To the best of our knowledge, this is the first study showing that distinct genetic variants of PEAR1 are associated with cardiovascular prognosis in high risk patients undergoing PCI and treated with dual anti platelet therapy.
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Stimpfle et al. (2018) conducted a cohort in Stable coronary artery disease (CAD) or acute coronary syndrome (ACS) (n=582). Homozygous PEAR1 rs2768759 minor allele vs. Major allele carriers was evaluated on Combined endpoint of time to death, myocardial infarction, or ischemic stroke (HR 3.16, 95% CI 1.4-7.13, p=0.006). Homozygous PEAR1 rs2768759 minor allele carriers had a significantly increased risk of the primary combined endpoint of death, myocardial infarction, or ischemic stroke compared to major allele carriers (HR 3.16).
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