Early-start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage and high risk of ischemic events (E-start):Protocol for a multi-centered, prospective, open-label, blinded endpoint randomized controlled trial

BACKGROUND: For severe spontaneous intracerebral hemorrhage (sSICH) patients with high risk of ischemic events, the incidence of postoperative major cardiovascular/cerebrovascular and peripheral vascular events (MACCPE) is notable. Although antiplatelet therapy is a potential way to benefit these patients, the severe hemorrhagic complications, e.g., intracranial re-hemorrhage, is a barrier for early starting antiplatelet therapy. OBJECTIVES: This randomized controlled trial aims to identify the benefit and safety of early starting antiplatelet therapy after operation for sSICH patients with high risk of ischemic events. METHODS: This study is a multicenter, prospective, randomized, open-label, blinded-endpoint trial. We will enroll 250 sSICH patients with a high risk of ischemic events (including cerebral infarcts, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep venous thrombosis). The participants will be randomized in a 1:1 manner to early-start group (start antiplatelet therapy at 3 days after operation) and normal-start group (start antiplatelet therapy at 30 days after operation). The early-start group will receive aspirin 100 mg daily. The control group will not receive antithrombotic therapy until 30 days after operation. The efficacy endpoint is the incidence of MACCPE, and the safety endpoint is the incidence of intracranial re-hemorrhage. DISCUSSION: The Early-Start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage trial (E-start) is the first randomized trial about early start antiplatelet therapy for operated sSICH patients with a high risk of ischemic events. This study will provide a new strategy and evidence for postoperative management in the future. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04820972; Available at: https://clinicaltrials.gov/ct2/show/NCT04820972?term=NCT04820972&draw=2&rank=1. Chinese Clinical Trial Registry, identifier ChiCTR2100044560; Available at: http://www.chictr.org.cn/showproj.aspx?proj=123277

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

Background Aspirin 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.Methods We 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.Results The 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 of GP1BA, TBXA2R, PTGS2 and NOS3 as 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).Conclusion GP1BA, TBXA2R, PTGS2 and NOS3 were SNPs related to ASR. The ASR-CN score is an effective tool to discriminate ASR patients, which may guide antiplatelet therapy.Clinical trial registration Surgical Treatments of Antiplatelet Intracerebral Hemorrhage cohort (unique identifier: ChiCTR1900024406, http://www.chictr.org.cn/edit.aspx?pid=40640&htm=4)