A 68-year-old Caucasian male patient presented to the emergency room with crushing chest pain, diaphoresis, and dyspnea. Chest pain was substernal, rated 7/10 in intensity, and radiating to both arms. Pain improved with administration of nitroglycerin. The patient was a former smoker with insulin-dependent type 2 diabetes mellitus, hypertension, and hyperlipidemia. He had been treated with percutaneous coronary intervention (PCI) with an earlier-generation drug-eluting stent to the left anterior descending artery 12 months ago for an anterior wall myocardial infarction (MI). An echocardiogram post-PCI showed normal left ventricular systolic function. He was treated with aspirin 81 mg daily, clopidogrel 75 mg daily, and atorvastatin 80 mg daily.
On exam, his body mass index was 30 kg/m2, temperature was 98.1° F, heart rate was 95 bpm, and blood pressure was 100/70 mmHg. The remainder of the cardiovascular exam was otherwise unremarkable. The patient stated that he had one episode of self-terminated gastrointestinal bleed 7 months prior and had briefly interrupted his antiplatelet therapy for 2 weeks. His electrocardiogram showed normal sinus rhythm with new ST-segment elevation with Q waves in leads V2-5 and reciprocal ST-segment depressions in leads III and aVF. Bedside echocardiogram showed new wall motion abnormality in the anterior wall. The patient was emergently taken to the cardiac catheterization laboratory and found have late stent thrombosis of the left anterior descending artery stent.
Which of the following is not true pertaining to this patient's current presentation?
Show Answer
The correct answer is: B. Prospective genotyping to assess if the patient has CYP2C19 loss-of-function genetic variation to guide appropriate antiplatelet agent post-PCI will reduce long-term ischemic coronary events.
Clopidogrel is the most frequently prescribed oral P2Y12 inhibitor for patients with acute coronary syndrome undergoing treatment with PCI with drug-eluting stent. Clopidogrel is a prodrug that requires the enzyme CYP2C19 for transformation into its active metabolite, which will then target the P2Y12 receptors on platelets, resulting in their inhibition.1 Theoretically, patients with CYP2C19 loss of function will have less platelet inhibition with clopidogrel. Up to 30% of the population have a CYP2C19*2 or CYP2C19*3 genotype that results in reduced or lost enzymatic function, translating to increased ischemic events. The TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention) trial, a prospective, open-label, multicenter, randomized clinical trial exploring genotype-guided P2Y12 inhibitor selection strategy compared to conventional management with clopidogrel, showed no significant difference in reduction of primary ischemic endpoint at 12 months in patients with acute coronary syndrome and stable coronary artery disease undergoing PCI who were treated with genotype-guided oral P2Y12 inhibitor versus the standard treatment with clopidogrel.2 The prospective genotyping arm (n = 2,652) underwent point-of-care genotyping. The patients were then divided, based on the results of this testing, into CYP2C19 loss-of-function carriers (CYP2C19*2 or CYP2C19*3) or carriers of the wild-type CYP2C19 gene allele. Carriers of the loss-of-function CYP2C19 allele were treated with ticagrelor 90 mg twice daily. Those with the wild type allele were treated with clopidogrel 75 mg daily. Patients randomized to the conventional care arm (n = 2,652) received clopidogrel 75 mg daily. After 12 months, retrospective genotyping was conducted in both groups of patients. The primary endpoint of the trial was a composite of cardiovascular death, MI, stroke, stent thrombosis, and severe recurrent ischemia during the first year after PCI. This endpoint was compared only among patients who had loss-of-function variance. A post hoc analysis found an 80% reduction in rate of ischemic events in the genotype-guided treatment arm in the first 3 months of treatment, but current evidence does not suggest a reduction in long-term ischemic coronary events with this strategy. Current clinical guidelines do not recommend testing for CYP2C19 genetic abnormality prior to prescribing clopidogrel (answer B). The TAILOR-PCI trial does suggest that point-of-care genotyping to guide antiplatelet therapy may help reduce ischemic events among patients who underwent PCI. Further results from extended follow-up study of the TAILOR-PCI trial are awaited to confirm or refute this signal of benefit.
Stent thrombosis is not a concern after balloon angioplasty. Balloon angioplasty has shown similar outcomes for deaths and MIs compared to bare-metal stent.3 Balloon angioplasty with provisional stenting is an acceptable strategy in patients at risk for interruption of antiplatelet therapy due to surgery or bleeding risk (answer A).
The ISAR-TEST 44 (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents-4) randomized trial evaluating the efficacy of newer-generation drug-eluting stent showed that patients treated with newer-generation drug-eluting stent had lower definite stent thrombosis events at 10 years' follow-up compared with patients treated with early-generation drug-eluting stent (answer C). Discontinuation of antiplatelet therapy, particularly in the first 6-12 months after index procedure, due to patient noncompliance, interruption for a procedure, or bleeding is an important predictor for stent thrombosis (answer D).5
Pereira NL, Farkouh ME, So D, et al. Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial. JAMA 2020;324:761-71.
Brophy JM, Belisle P, Joseph L. Evidence for use of coronary stents. A hierarchical bayesian meta-analysis. Ann Intern Med 2003;138:777-86.
Kufner S, Joner M, Thannheimer A, et al. Ten-Year Clinical Outcomes From a Trial of Three Limus-Eluting Stents With Different Polymer Coatings in Patients With Coronary Artery Disease. Circulation 2019;139:325-33.
Windecker S, Meier B. Late coronary stent thrombosis. Circulation 2007;116:1952-65.
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