Outcomes of Genotype-Guided Antiplatelet Therapy

Study Questions:

What are the outcomes following clinical implementation of CYP2C19 genotype–guided antiplatelet therapy after percutaneous coronary intervention (PCI)?

Methods:

The study investigators conducted a multicenter investigation of clinical CYP2C19 genotype–guided antiplatelet therapy post-PCI. After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (MACE) (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele who were prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.

Results:

Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for MACE was significantly higher in patients with a loss-of-function allele who were prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio [aHR], 2.26; 95% confidence interval [CI], 1.18-4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (aHR, 2.87; 95% CI, 1.35-6.09; p = 0.013). There was no difference in MACE between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (aHR, 1.14; 95% CI, 0.69-1.88; p = 0.60).

Conclusions:

The authors reported a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy was prescribed.

Perspective:

This study reports a higher risk for a MACE in patients with CYP2C19 loss-of-function alleles who are treated with clopidogrel versus alternative antiplatelet therapy. Most events occurred in patients with acute coronary syndrome indications at the index PCI, in whom the risk for a MACE was higher in loss-of-function clopidogrel versus loss-of-function alternative patients. Given the lack of a control group, nonrandomized nature of the study, lack of event adjudication, and lack of data on bleeding, the study findings need to be validated prospectively in a well-designed trial, prior to advocating routine genotyping for CYP2C19 loss-of-function alleles after PCI.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, EP Basic Science, Interventions and ACS

Keywords: Acute Coronary Syndrome, Adenosine, Alleles, Genotype, Myocardial Infarction, Platelet Aggregation Inhibitors, Purinergic P2Y Receptor Antagonists, omega-Chloroacetophenone, Percutaneous Coronary Intervention, Pharmacogenetics, Stroke, Treatment Outcome


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