Ticagrelor resistance: a case series and algorithm for management of non-responders

Laurent, Dimitri; Dodd, William; Small, Coulter; Gooch, M. Reid; Ghosh, Rajesh; Goutnik, Michael; Blatt, Tasha; Porche, Ken; Geh, Ndi; Adamczak, Stephanie; Polifka, Adam; Brzezicki, Grzegorz; Hoh, Brian L.; Chalouhi, Nohra

doi:10.1136/neurintsurg-2021-017638

Cited by 8 publications

(3 citation statements)

References 110 publications

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“…On one hand, Clopidogrel is administered as a prodrug, and we must wait for it to become bioactive through hepatic metabolism [ 36 ], and then conduct a multiplate test. On the other hand, approximately one third of patients are non-responders to Clopidogrel, whereas non-responders to Ticagrelor are very rare [ 37 ]. As a result, administering Ticagrelor after stenting is less critical, as there is reduced uncertainty following the medication’s administration.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety Outcomes for Acute Ischemic Stroke Patients Treated with Intravenous Infusion of Tirofiban After Emergent Carotid Artery Stenting

Garayzade,

Berlis,

Schiele

et al. 2023

Clin Neuroradiol

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Introduction Emergent stenting of the extracranial internal carotid artery (ICA) in stroke patients requires antiplatelet therapy to prevent in-stent thrombosis with a higher risk of intracranial haemorrhage. Aim of the Study Assess the efficacy and safety of emergent carotid stenting with intravenous tirofiban in acute ischemic stroke patients. Methods Primary endpoint: symptomatic hemorrhage. Secondary endpoints: 90-day functional outcome and mortality. Results Of the 62 patients, 21 (34%) received tirofiban as a single antiplatelet, and 41 (66%) received combined therapy. Premedication with anticoagulants and antiplatelets was significantly more frequent in the tirofiban-only group. The rate of symptomatic haemorrhage was significantly lower in the tirofiban-only group than in the combined group (4.8% vs. 27%, p = 0.046). The patients with tirofiban alone had a significantly better functional outcome at day 90 than the combined group (52% vs. 24%, p = 0.028). Mortality was equal (24%) in both groups. Pre-interventional NIHSS score (p = 0.003), significant blood pressure fluctuations (p = 0.012), tandem occlusion (p = 0.023), and thrombolysis (p = 0.044) showed relevant influence on the rate of symptomatic hemorrhage in the entire patient cohort. Conclusions A single antiplatelet therapy with tirofiban regardless of the premedication may improve the functional outcome in patients with stroke due to acute extracranial carotid lesion and emergent carotid stenting with lower rates of serious intracranial haemorrhage. For patients with high pre-interventional NIHSS score, tandem occlusion and after pre-interventional thrombolysis, caution is advised. Additionally, strict blood pressure monitoring should be conducted during the first 72 h after intervention.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety Outcomes for Acute Ischemic Stroke Patients Treated with Intravenous Infusion of Tirofiban After Emergent Carotid Artery Stenting

Garayzade,

Berlis,

Schiele

et al. 2023

Clin Neuroradiol

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“…Ticagrelor has been considered a new P2Y 12 inhibitor and has reportedly overcome clopidogrel resistance. Although ticagrelor non-responders only account for 3% of patients with ACS, the pathological consequences can be devastating (Thomas and Storey, 2016;Laurent et al, 2021). Currently, the US Food and Drug Administration (FDA) reported that ticagrelor does not need dose adjustment for different races.…”

Section: Discussionmentioning

confidence: 99%

Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers

et al. 2022

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Background: Ticagrelor belongs to a new class of P2Y12 receptor inhibitor that has been widely used for antiplatelet therapy. This study aimed to explore the effect of single nucleotide polymorphisms (SNPs) in metabolic enzymes, transporters, and other relevant variants on the pharmacokinetics (PK) of ticagrelor and its active metabolite, AR-C124910XX.Methods: The study population comprised 68 healthy Chinese volunteers who were enrolled in a ticagrelor bioequivalence clinical trial. The PK profile of ticagrelor was evaluated after orally administering a single 90-mg dose of ticagrelor in tablet form. The plasma concentrations of ticagrelor and AR-C124910XX were determined through liquid chromatography–tandem mass spectrometry. Plasma DNA samples were used to explore the effect of gene polymorphisms on the PK of ticagrelor and AR-C124910XX with whole-exome sequencing.Results: Female participants had a higher maximum plasma concentration/weight ratio (Cmax/W; p < 0.001) and a shorter half-life (T1/2; p < 0.05) for ticagrelor than their male counterparts. In addition, a higher area under the curve/weight ratio (AUC/W; p < 0.001), and longer T1/2 (p < 0.001) and time to reach the maximum plasma concentration (Tmax; p < 0.001), as well as a lower apparent drug clearance (CL/F; p < 0.001), were observed among healthy volunteers in the fed trial compared to those enrolled in the fasting trial. For AR-C124910XX, higher Cmax/W (p < 0.001) and AUC/W (p < 0.001) but lower CL/F (p < 0.001) and apparent volume of distribution (Vd/F; p < 0.001) were observed among female participants. Healthy volunteers enrolled in the fasting trial exhibited higher Cmax/W (p < 0.001) and AUC/W (p < 0.01), shorter Tmax (p < 0.001), and lower CL/F (p < 0.001) and Vd/F (p < 0.001) than those enrolled in the fed trial. Upon confirmation through multivariate analysis, the CYP4F2 rs2074900 A/A carriers were associated with higher Cmax/W and AUC/W and lower CL/F and Vd/F than the CYP4F2 rs2074900 A/G and G/G carriers.Conclusion: This study is the first to show that the CYP4F2 rs2074900 SNP had a remarkable effect on ticagrelor PK, which is significant since it adds to the limited pharmacogenetic information on ticagrelor.

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“…Numerous other studies have also demonstrated variability in physician practice habits in the use of platelet and genetic testing for aspirin and clopidogrel resistance, despite the widely known and described variability in genetic and metabolic pathways across our patient population 2–9. Even though antiaggregate and anticoagulant guidance is slightly more developed in the acute ischemic stroke space, significant variability still exists.…”

mentioning

confidence: 95%

A pressing need and opportunity to standardize care in neurointerventional surgery

Leacy

Caroff

2022

J NeuroIntervent Surg

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Ticagrelor resistance: a case series and algorithm for management of non-responders

Cited by 8 publications

References 110 publications

Efficacy and Safety Outcomes for Acute Ischemic Stroke Patients Treated with Intravenous Infusion of Tirofiban After Emergent Carotid Artery Stenting

Efficacy and Safety Outcomes for Acute Ischemic Stroke Patients Treated with Intravenous Infusion of Tirofiban After Emergent Carotid Artery Stenting

Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers

A pressing need and opportunity to standardize care in neurointerventional surgery

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