Model based on single-nucleotide polymorphism to discriminate aspirin resistance patients

Abstract

BackgroundAspirin is widely used for preventing ischaemic events. About 20%–40% of patients have aspirin resistance (ASR), which prevents them from benefiting from aspirin medication. This study aimed to develop and validate a model based on single-nucleotide polymorphism (SNP) to distinguish ASR patients.MethodsWe included patients with spontaneous intracerebral haemorrhage and continuing antiplatelet therapy from a multicentre, prospective cohort study as the derivation cohort. Thromboelastography (inhibition of arachidonic acid channel<50%) was used to identify ASR. Genotyping was performed to identify the ASR-related SNP. Based on the result of the logistic analysis, the aspirin resistance in the Chinese population score (ASR-CN score) was established, and its accuracy was evaluated using the area under the curve (AUC). Patients receiving dual antiplatelet therapy for unruptured intracranial aneurysm embolism were prospectively included in the validation cohort. After embolism, 30-day ischaemic events, including ischaemic stroke, new or more frequent transient ischaemic attack, stent thrombosis and cerebrovascular death, were recorded.ResultsThe derivation cohort included 212 patients (155 male patients and the median age as 59). 87 (41.0%) individuals were identified with ASR. The multivariate logistic analysis demonstrated six SNPs ofGP1BA, TBXA2R, PTGS2andNOS3as risk factors related to ASR. The ASR-CN score integrating these SNPs performed well to discriminate ASR patients from non-ASR patients (AUC as 0.77). Based on the validation cohort of 372 patients receiving antiplatelet therapy after embolism (including 130 ASR patients), the ASR-CN score continued to distinguish ASR patients with good accuracy (AUC as 0.80). Patients with high a ASR-CN score were more likely to suffer from 30-day ischaemic events after embolism (OR, 1.28; 95% CI, 1.10 to 1.50; p=0.002).ConclusionGP1BA, TBXA2R, PTGS2andNOS3were SNPs related to ASR. The ASR-CN score is an effective tool to discriminate ASR patients, which may guide antiplatelet therapy.Clinical trial registrationSurgical Treatments of Antiplatelet Intracerebral Hemorrhage cohort (unique identifier: ChiCTR1900024406,http://www.chictr.org.cn/edit.aspx?pid=40640&htm=4).

Epoxidase inhibitor-aspirin resistance and the relationship with genetic polymorphisms: a review

“…11 In addition, laboratory tests have found that in some patients aspirin does not inhibit thromboxane A2 production, which is called biochemical aspirin resistance. 12 At present, studies have shown that there are many reasons leading to aspirin resistance, such as poor drug compliance and insufficient drug dose, non-cyclooxygenase 1 mediated platelet activation, obesity and gene polymorphisms; [13][14][15][16] of which gene polymorphisms are the focus of considerable research in aspirin resistance at present. [17][18][19][20] Platelets contain a large number of highly polymorphic transmembrane glycoprotein receptors encoded by two or more isomeric alleles.…”