Aug 2026· Neuroprotection· 0 citations· 90 references
Medicine
TL;DR
The current landscape of PFT‐guided individualized antiplatelet therapy in cerebral infarction is reviewed, with the aim of summarizing existing evidence and offering suggestions for future research.
Abstract
Abstract Current evidence indicates that antiplatelet therapy as a cornerstone for secondary prevention of cerebral infarction. However, ischemic or bleeding events arising from antiplatelet drug resistance or excessive platelet inhibition can diminish its clinical benefit. These challenges have laid the foundation for individualized antiplatelet treatment. Although cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genetic polymorphisms have partially addressed the issue of drug resistance in these patients, they remain insufficient to resolve the high incidence of both ischemic and bleeding events. Platelet function testing (PFT)‐guided antiplatelet therapy has been proven beneficial in patients after percutaneous coronary intervention, yet its efficacy in patients with cerebral infarction remains controversial. Platelet function provides a direct and comprehensive reflection of antiplatelet effects, offering potential not only to overcome drug resistance but also to guide de‐escalation strategies, thereby mitigating the frequent occurrence of both ischemic and bleeding events in cerebral infarction. Overall, the current application of PFT to guide personalized antiplatelet regimens in patients with cerebral infarction is characterized by considerable variability. In light of recent advances in this field, we herein review the current landscape of PFT‐guided individualized antiplatelet therapy in cerebral infarction, with the aim of summarizing existing evidence and offering suggestions for future research.
Clopidogrel, as an antiplatelet drug, is important for the treatment of the secondary prevention of ischemic stroke according to the latest guidelines on ischemic stroke management. However, some patients still fail to achieve a drug response and experience ischemic events despite taking clopidogrel, due to differences in the production of active metabolites attributable to specific factors. While platelet function testing play a crucial role in evaluating the efficacy of antiplatelet drugs, research on their application remains relatively limited in the ischemic stroke population; thus, it is necessary to clarify their role in guiding individualized treatment for patients with ischemic stroke. In this review, we synthesize the current state of research on clopidogrel resistance in patients with ischemic stroke, covering key aspects such as the pharmacological mechanisms and metabolism of clopidogrel, the risk factors associated with clopidogrel resistance, and the clinical application of platelet function testing in ischemic stroke. Our study aims to explore the prevalence and predictors of clopidogrel resistance among ischemic stroke patients, identify its potential impact on recurrent ischemic stroke, and thereby offer insights for the development of personalized and precision treatment strategies for clopidogrel treatment in these patients.
Wei-Hua Li, Yan Zhao, Mengchen Yu et al.· Journal of Cardiovascular Ph...· 0 citations
Platelets are central to hemostasis and thrombosis. Excessive platelet activation contributes to arterial thrombotic events, including myocardial infarction, ischemic stroke, and complications of peripheral artery disease, whereas excessive platelet inhibition increases bleeding risk. Antiplatelet therapy remains a cornerstone of secondary prevention in atherosclerotic and thrombotic cardiovascular diseases, yet current treatment paradigms do not fully account for biological heterogeneity in platelet function, including differences related to sex, age, hormonal status, and disease context. This state-of-the-art review examines current antiplatelet strategies, fundamental mechanisms of signal transduction, clinical indications, limitations of preclinical and clinical studies, focusing on sex-specific considerations and opportunities for personalized antiplatelet therapy. Aspirin and P2Y12 receptor antagonists are widely used for secondary prevention. However, women have been underrepresented in many pivotal clinical trials, limiting the precision of sex-specific estimates of efficacy and bleeding risk. In parallel, commonly used preclinical models often fail to recapitulate the physiological conditions in which platelets interact with the vasculature, leukocytes, and soluble factors. Emerging therapeutic approaches seek to refine platelet inhibition by targeting pathways that reduce thrombotic risk while preserving hemostasis. Advancing antiplatelet therapy will require integration of mechanistic platelet biology with diverse clinical trial populations, standardized platelet phenotyping, and disease-specific approaches that account for how platelet function is remodeled across health and vascular disease.
Anu Aggarwal, Tessa J. Barrett, P. Mehta et al.· Circulation Research· 0 citations
Injectable antiplatelet agents can provide immediate and effective platelet inhibition in patients with acute coronary syndromes (ACS). These agents are able to overcome many of the limitations of oral antiplatelet agents, and maybe of particular benefit in patients with ST-elevation myocardial infarction (STEMI), especially those presenting with cardiogenic shock or rescuscitated cardiac arrest. In these patients, factors such as vomiting, altered physiology, sedation, mechanical ventilation or therapeutic hypothermia can impair drug absorption, reducing the intended antiplatelet effect and increasing ischaemic risk. Intravenous aspirin is used widely in patients with ACS, while the absorption of oral P2Y12 inhibitors is often delayed, and the intravenous P2Y12 inhibitor cangrelor can achieve almost complete platelet inhibition within minutes. While use of the glycoprotein IIb/IIIa inhibitors (GPI) eptifibatide and tirofiban is decreasing, typically reserved for thrombotic complications or no reflow following PCI, recently zalunfiban, a novel subcutaneously administered GPI has been shown to improve reperfusion before revascularisation in patients with STEMI when given at first medical contact. In this review, we dicuss the rationale and potential benefits of injectable antiplatelet medications, including currently available agents and those in development or being tested in clinical trials. While the benefit of injectable medications on hard clinical endpoints such as major adverse cardiac events remains unclear for an allcomers ACS population, there is emerging data that these agents achieve rapid platelet inhibition, improve coronary flow and clinical outcomes particular in high risk ACS patients, such as those with cardiogenic shock.
U. Zeymer, S. Koolaji, D. Araiza-Garaygordobil et al.· European heart journal. Acut...· 0 citations
Cardiovascular diseases remain the leading global cause of morbidity and mortality, and thrombotic events contribute substantially to their clinical burden. Established anticoagulants, including vitamin K antagonists and direct oral anticoagulants, reduce thromboembolic events but remain limited by bleeding risk in selected patients. Factor XI (FXI), a serine protease in the intrinsic coagulation pathway, has emerged as a promising investigational target because FXI-dependent thrombin amplification appears to contribute more to pathological thrombosis than to physiological hemostasis. This review consolidates contemporary progress in FXI/activated factor XI (FXIa)-targeted therapeutics, encompassing monoclonal antibodies (e.g., abelacimab, osocimab), antisense oligonucleotides (e.g., fesomersen), and small-molecule inhibitors (e.g., milvexian, asundexian). Clinical evidence suggests that FXI/FXIa inhibition may reduce thrombosis or bleeding in selected settings, particularly postoperative venous thromboembolism prophylaxis and certain high-bleeding-risk populations; however, efficacy signals have been inconsistent across indications such as atrial fibrillation, acute coronary syndrome, and secondary stroke prevention. Remaining challenges, including long-term safety, dose selection, patient stratification, perioperative management, and definitive efficacy in outcome trials, are also discussed. Overall, FXI/FXIa inhibition remains a promising but still investigational strategy that may improve the balance between antithrombotic efficacy and bleeding risk in selected clinical contexts.
Zhaowei Zhu, W. Gong, Xinqun Hu et al.· Vessel Plus· 0 citations
Insufficient response to aspirin is associated with increased cardiovascular risk, but its prognostic relevance in patients receiving potent P2Y12 inhibitors remains uncertain. We assessed methods to identify high on-treatment platelet reactivity (HTPR) under aspirin and evaluated the impact of potent versus less potent P2Y12 inhibition in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).
Platelet function was analyzed in 757 aspirin-pretreated CAD patients treated with clopidogrel (
n
= 406), ticagrelor (
n
= 152), or prasugrel (
n
= 165). Antiplatelet efficacy was assessed using multiple electrode aggregometry (MEA), platelet function analyzer-100 (PFA-100
®
), cone and platelet analyzer (CPA), and serum thromboxane B2 (TXB2). All-cause mortality was assessed over five years, and major bleeding and major adverse cardiac events (MACE) over one year.
AA-induced MEA > 6 U was associated with higher long-term mortality, however, discriminatory performance was modest (AUC = 0.575,
p
= 0.051), while CPA-SC < 6% strongly predicted major bleeding (AUC = 0.759,
p
= 0.001). None of the aspirin-related assays predicted MACE. Prasugrel or ticagrelor treatment was associated with lower long-term mortality than clopidogrel (HR = 0.411; 95% CI: 0.27–0.62;
p
< 0.001). Concomitant use of potent P2Y12 inhibitors and aspirin resulted in fewer aspirin semi- or non-responders and lower rates of dual HTPR. Dual HTPR occurred in ~ 1% of ticagrelor-, 2% of prasugrel-, and 7% of clopidogrel-treated patients.
Exploratory analyses suggested that AA-MEA and CPA-SC were associated with long-term mortality and major bleeding, respectively. Given the modest discriminatory performance of AA-MEA, these findings require external validation. Potent P2Y12 inhibitors reduced dual HTPR, while platelet function assays provided complementary prognostic information in CAD.
Jovan Rogozarski, C. Kronberger, C. Skos et al.· BMC Cardiovascular Disorders· 0 citations
Ischemic stroke remains a leading cause of death and disability worldwide, and bleeding (particularly intracranial hemorrhage) continues to limit conventional antithrombotic therapy in secondary prevention, even with direct oral anticoagulants. Factor XI (FXI) has emerged as a promising target: it amplifies thrombin generation and stabilizes pathological thrombi while contributing only marginally to physiological hemostasis, as illustrated by the mild bleeding phenotype of congenital FXI deficiency. This biological dissociation underpins the concept of hemostasis‐sparing anticoagulation. Three pharmacological classes are being studied, with distinct pharmacokinetic, pharmacodynamic, and drug‐drug interaction profiles: small‐molecule oral FXIa inhibitors (asundexian and milvexian), FXI antisense oligonucleotides (fesomersen), and monoclonal antibodies targeting FXI/FXIa (abelacimab and osocimab). Oral small molecules offer rapid, reversible target engagement particularly suited to chronic cerebrovascular prevention. While phase II trials (PACIFIC‐Stroke, AXIOMATIC‐SSP) showed neutral primary endpoints with reassuring safety, the phase III OCEANIC‐STROKE trial demonstrated that asundexian 50 mg once daily, added to antiplatelet therapy, reduced recurrent ischemic stroke by 26% (HR 0.74; 95% CI 0.65–0.84) without significant bleeding excess in non‐cardioembolic stroke; the ongoing LIBREXIA‐STROKE is testing milvexian 25 mg twice daily in a similar setting. Conversely, OCEANIC‐AF showed that FXIa inhibition alone is insufficient versus apixaban in atrial fibrillation, indicating dependence upon clinical setting and suggesting the need for a precision‐medicine approach integrating clinical, imaging, and biomarker‐based patient stratification. This narrative review integrates pathophysiological rationale, comparative pharmacology of all FXI‐targeting classes, trial evidence, and patient stratification, providing an up‐to‐date reference for FXI/FXIa inhibition in secondary ischemic stroke prevention.
F. Ferrari, R. F. Villa· Journal of clinical pharmaco...· 0 citations
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