Dual antiplatelet therapy consisting of aspirin and clopidogrel is the standard of care for neurointerventional stenting and flow diversion. Platelet function testing has been increasingly performed to identify patients with a hypo- or hyper-response to clopidogrel. Ticagrelor has been a popular alternative antiplatelet agent for such patients. We assessed the role of platelet function testing in patients receiving ticagrelor and undergoing stenting or flow diversion.
The data from patients who had undergone stent-assisted coiling or Pipeline flow diversion of a cerebral aneurysm with ticagrelor therapy at any point during their treatment course from May 2017 to August 2019 at a single academic institution in the United States were retrospectively reviewed. Platelet function testing was used to determine the P2Y12 reactive units (PRUs), and the results were correlated with the procedural complications.
A total of 28 patients with 29 aneurysms were treated while receiving ticagrelor. Of the 29 aneurysms, 16 (55.2%) were treated with flow diversion and 13 (44.8%) with stent-assisted coiling. Four thromboembolic complications (13.8%) and no hemorrhagic complications developed. Of the 8 patients with ≥1 PRU value >100, 4 (50%) had experienced a thromboembolic complication. The patients without a PRU value >100 did not experience any complications.
A risk of thromboembolic complications exists for patients receiving ticagrelor, which correlated with the PRUs in the present preliminary study. The findings from the present study suggest that the safe PRU range for patients receiving ticagrelor should be shifted to 0-100, which is lower than that of clopidogrel, thought to be 60-210. Further validation of the optimal PRU range for patients receiving ticagrelor is necessary.

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Dual antiplatelet therapy with aspirin and a thienopyridine reduces ischemic cardiovascular events following percutaneous coronary intervention. However, despite this treatment, residual risk of ischemic events persists. Among other factors, enhanced platelet reactivity after thienopyridine therapy is associated with an increased risk of ischemic cardiovascular events. A heterogeneous and variable patient response to the thienopyridine clopidogrel exists and has been attributed to a number of genetic, pharmacologic, and clinical factors. Developments in point-of-care platelet function testing allow for the assessment of on-treatment platelet reactivity after thienopyridine therapy and thus identify poor responders. We report two cases of stent thrombosis in which the bedside rapid platelet function VerifyNow P2Y12 Assay® (Accumetrics, San Diego, CA) was used to determine on-treatment platelet reactivity and identify potential etiologies of the thrombotic events.

BACKGROUND: Insufficient platelet inhibition is a major determinant of stent thrombosis (STh), although the etiology is multifactorial. On-clopidogrel platelet reactivity was investigated in patients with previous angiographically confirmed STh, myocardial infarction (MI), and controls.
METHODS: Using the Swedish Coronary Angiography and Angioplasty Registry, we identified patients with angiographically confirmed STh (n = 48) or MI (n = 30) while on dual antiplatelet therapy within 6 months of percutaneous coronary intervention (PCI) and matched control patients (n = 78). On-clopidogrel platelet reactivity was measured with VerifyNow P2Y12 and vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay.
RESULTS: The mean P2Y12 reaction units (PRU) was higher (246.8 ± 75.9 vs 200.0 ± 82.7, P = .001) in STh patients compared with controls. The optimal cutoff for STh was 222 PRU or higher (area under the curve 0.69, P < .0001) in a receiver operating characteristics (ROC) analysis. The cutoff level resulted in 70.2% sensitivity and 67.3% specificity. There was no significant difference in mean PRU but a higher device-reported percent inhibition (45.1 ± 23.8 vs 32.1 ± 23.2, P = .04) in patients with MI compared with controls. Results with the VASP phosphorylation assay were not related to the occurrence of STh or MI.
CONCLUSIONS: STh was associated with high on-clopidogrel platelet reactivity measured with VerifyNow (cutoff level of PRU ≥222) but spontaneous MI in stented patients on clopidogrel treatment was not. There was, however, a substantial overlap in on-clopidogrel platelet reactivity between patients with and without on-treatment STh questioning the clinical use of platelet function testing to identify patients at high risk for STh.

BACKGROUND: We recently described a gain-of-function haplotype, called H2, of the adenosine diphosphate (ADP) receptor P2Y12 gene associated with increased ADP-induced platelet aggregation ex vivo in healthy volunteers. Because platelets play a key role in atherosclerosis and arterial thrombosis, we tested the possible link between the H2 haplotype and the risk of peripheral arterial disease (PAD) in a case-control study.
RESULTS: We studied 184 consecutive male patients under 70 years of age with PAD and 330 age-matched control subjects free of symptomatic PAD and with no cardiovascular history. Mean age was 57.1+/-7.2 years (cases) and 56.7+/-7.6 years (control subjects). The H2 haplotype was more frequent in patients with PAD than in control subjects (30% and 21%, respectively; OR, 1.6; CI, 1.1 to 2.5; P=0.02 in univariate analysis). This association with PAD remained significant in multivariate regression analysis (OR, 2.3; CI, 1.4 to 3.9; P=0.002) after adjustment for diabetes, smoking, hypertension, hypercholesterolemia, and other selected platelet receptor gene polymorphisms.
CONCLUSIONS: These data point to a role of the H2 haplotype in atherosclerosis and raise the possibility of relative thienopyridine resistance in carriers of the P2Y12 H2 haplotype.