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Results for “Platelet Aggregation”

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At least 19 recordsLinked to original sources

PubMed2026

Tanshinone IIA impairs platelet function and thrombus formation.

BACKGROUND: Tanshinone IIA (T-IIA) is a fat-soluble active ingredient derived from the traditional Chinese medicine Danshen and possesses cardioprotective property. However, its exact role in platelet function is unknown. OBJECTIVES: This study investigated T-IIA's role in platelet aggregation, granules release, spreading, clot retraction, as well as in vivo hemostasis and thrombus formation. METHODS: Human platelets were treated with different doses of T-IIA (10, 50, and 100 μM) to measure platelet function and activation. In addition, T-IIA was administrated into wild-type mice to evaluate hemostasis and thrombus formation. RESULTS: T-IIA significantly impaired platelet aggregation, adenosine triphosphate secretion, P-selectin expression, and spreading and clot retraction dose dependently without affecting the expression profiles of αIIbβ3 and glycoprotein VI or Ibα. Administration of T-IIA significantly prolonged mice tail bleeding time and inhibited arterial and venous thrombosis. Further analysis showed that T-IIA dose dependently reduced platelet reactive oxygen species generation. Quantitative proteomic and phosphoproteimic assays analyzing T-IIA-treated vs vehicle-treated platelets after stimulation identified dysregulated phosphorylation of several proteins, which were enriched in platelet activation. Among the downregulated phosphoproteins, Rho-associated protein kinase (ROCK)1, integrin β3, and talin1 exhibited the lower fold change of phosphorylation in T-IIA-treated platelets compared with those in vehicle-treated platelets. Consistently, T-IIA treatment inhibited the phosphorylation of ROCK1, p47phox, integrin β3, and talin1 in activated platelets. CONCLUSION: T-IIA impairs platelet function and thrombosis via inhibition of several signaling pathways including ROCK1/p47phox, β3, and talin1, implying that T-IIA may represent a promising therapeutic candidate for treating thrombotic diseases.

Animals↗

PubMed2026

A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.

Hemostasis and thrombosis are strongly dependent on the unique ability of platelets to rapidly activate integrin receptors and to firmly adhere to sites of injury under shear stress conditions. Central to integrin activation is the small GTPase RAP1, which itself is activated by guanine nucleotide exchange factors (GEFs). CalDAG-GEFI (RASGRP2) is the highest expressed and functionally dominant platelet RAP-GEF. However, a genome-wide association study also suggested a significant role for RAPGEF2 (PDZ-GEFI), a low-expressed RAP-GEF, in human platelet aggregation. Here, we used mice deficient in RAPGEF2 (megakaryocyte-specific, Rapgef2mKO), CalDAG-GEFI (Caldaggef1-/-), or both RAPGEF2 and CalDAG-GEFI (DKO) to characterize the contribution of RAPGEF2 signaling to platelet function, hemostasis, and thrombosis. RAPGEF2 protein was detected in murine and human platelets. Compared with control or Caldaggef1-/- platelets, both RAP1 activation and integrin αIIbβ3-mediated aggregation were significantly diminished in DKO platelets. When compared with controls, Rapgef2mKO platelets exhibited reduced integrin activation, a more reversible aggregation response, and impaired adhesion under conditions of shear stress ex vivo and in vivo. Mechanistic studies strongly suggest that RAPGEF2 operates downstream of receptors coupled to the heterotrimeric G protein G13 (GNA13), such as αIIbβ3 and the thromboxane receptor. Together, our studies provide genetic evidence that RAPGEF2 in platelets operates downstream of G13 as an important regulator of RAP1 signaling and integrin activation, especially under conditions of elevated shear stress. These findings markedly improve our understanding of G protein signaling and integrin function in platelets, with potential implications for the development of improved platelet-targeted therapies for cardiovascular disease.

Animals↗

PubMed2026

Inherited Platelet GPIV Deficiency: First Description of a Series of Unrelated Patients with Bleeding Diathesis.

GPIV (CD36) is a multifunctional membrane protein expressed on various cells, including platelets, where it plays a role in adhesion and activation through the interaction with its ligands, including collagen types I and III and thrombospondin 1. Inherited GPIV deficiency, historically recognized in anti-Naka alloimmunized East Asian donors, is considered asymptomatic and associated with normal platelet aggregation, although impaired adhesion under high-flow conditions has been reported. Here, we reconsider the molecular basis, epidemiology and functional consequences of GPIV deficiency and report four unrelated patients in whom heterozygous CD36 variants are associated with markedly reduced platelet GPIV expression and a clinically relevant mucocutaneous bleeding diathesis. Patients suffered lifelong bleeding symptoms despite normal light-transmission aggregometry and platelet granule content and release and displayed decreased GPIV expression. Three of them showed slightly decreased VWF. Platelet adhesion to Type I collagen was reduced at high shear. These cases suggest for the first time an association between CD36 gene variants and bleeding and underscore the importance of including GPIV in the diagnostic workup of inherited platelet disorders, particularly when conventional assays do not reveal abnormalities.

Humans↗

PubMed2026

Reduced platelet formation associated with serine metabolic dysregulation in integrin αIIbβ3-deficient megakaryocytes.

Glanzmann thrombasthenia (GT) is characterized by absent platelet aggregation in response to all agonists except ristocetin and is caused by recessive inactivating variants in ITGA2B or ITGB3. Although patients with GT typically are described as having normal platelet counts, autosomal dominant activating variants in ITGA2B or ITGB3 cause macrothrombocytopenia. Interestingly, in our cohort of 16 patients with GT, 8 consistently exhibited platelet counts at the lower end of the normal range. We studied the role of integrin αIIbβ3 in platelet formation using megakaryocytes (MKs) derived from genetically modified immortalized MK cell lines (imMKCLs), focusing on 2 modifications of ITGB3: ITGB3-/- (inactivating) and ITGB3WT/D673_E713del (activating). In static differentiation cultures, ITGB3-/- and ITGB3WT/D673_E713del imMKCLs exhibited normal MK differentiation but reduced proplatelet formation. Platelet production was also impaired in a 3-dimensional silk-based bone marrow system and in shaking cultures, confirming a quantitative role for ITGB3 in platelet production independent of the type of variant. Although thrombin receptor activating protein-activated, in vitro-generated platelets lacking αIIbβ3 failed to bind the activation-dependent PAC-1 antibody, ITGB3WT/D673_E713del platelets bound PAC-1 before activation, mimicking the patient's phenotype. Transcriptome profiling and metabolomic analyses of integrin αIIbβ3-deficient MKs revealed impaired serine metabolism and downregulation of SLC3A2 (CD98hc), an amino acid transporter chaperon known to interact with the β3 subunit. Flow cytometry confirmed decreased CD98hc in mutant MKs, whereas reexpression of wild-type ITGB3 in ITGB3-/- MKs restored αIIbβ3 and CD98hc expression, normalized proplatelet formation, and enhanced serine uptake. These results uncover a previously unrecognized role of integrin αIIbβ3 in coupling serine metabolism to platelet biogenesis.

Humans↗

PubMed2026

Development of Dual-Cross-Linked AlgMA/HAMA Hybrid Hydrogels for Traumatic Wound Healing.

Traumatic injuries and uncontrolled, intense bleeding caused by surgery remain among today's leading medical problems. Traumatic wounds are not only observed on the skin but also result from internal organ ruptures caused by explosions and firearms. At this point, severe hemorrhaging can lead to hypothermia, hemorrhagic shock, organ failure, and even death due to the loss of more than 40% of blood volume. Therefore, it is crucial to halt bleeding rapidly. In this study, an alginate derivative that supports platelet aggregation and a hyaluronic acid derivative that adheres to wet tissues and induces angiogenesis, thereby promoting vascularization, have been prepared. The derivatives of alginate and hyaluronic acid were subjected to free radical photopolymerization, allowing them to cross-link in the presence of visible light. The study aims to introduce a new biomaterial featuring sodium alginate and hyaluronic acid groups that demonstrates good mechanical strength, a high swelling capacity to stabilize bleeding in the environment, and effective hemostatic properties. The chemical characterization of biopolymers was analyzed using FTIR and NMR techniques. The mechanical properties, swelling behavior, and degradation profiles of visible light cross-linked hybrid hydrogels were systematically characterized. The biocompatibility of the produced hydrogels was also evaluated using MTT and scratch wound healing tests. In addition, hemolysis and blood coagulation tests were performed to investigate the hemocompatibility and hemostatic potential of visible light cross-linked hybrid hydrogels.

Journal Article↗

PubMed2025

Proteomic insights into platelet dysregulation and pathogenic mechanisms of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Undissolved thrombus blocks the pulmonary arteries in chronic thromboembolic pulmonary hypertension (CTEPH), a potentially fatal illness that raises pulmonary resistance, causes right heart failure, and even results in death. Although platelets are linked to vascular dysfunction and thrombus formation, it is yet unknown what precise proteome alterations and mechanistic roles they play in CTEPH. METHODS: We extracted platelet-rich plasma from peripheral blood and separated the plasma to obtain enriched platelet pellet (EPP). Quantitative proteomics was used to examine EPP from CTEPH patients and healthy controls using mass spectrometry. The relationship between protein levels and clinical markers of right heart function was examined. Platelet activity, morphology, and interactions with other blood components were evaluated using transmission electron microscopy, immunofluorescence, and flow cytometry. RESULTS: The proteomic investigation found that 179 proteins were differentially expressed in CTEPH patients. The analysis revealed that these proteins were involved in crucial processes such as complement and coagulation cascades, phagosome, and neutrophil extracellular trap (NET) formation. Elevated proteins, specifically NOX2, PAD4, ITGB2, and HMGB1, have been associated to platelet-neutrophil aggregates and NET formation. In addition, enhanced P-selectin expression in platelets and plasma confirmed greater platelet activation in CTEPH patients. Notably, PAD4 and NOX2 levels showed a substantial correlation with hemodynamic parameters and right heart dysfunction. MPO-DNA, a NET marker associated with P-selectin and ITGB2 expression, was discovered in higher concentrations in CTEPH patients' plasmas. CONCLUSION: Platelet aggregation and activation in CTEPH encourage the formation of NETs, which advances the disease and prolongs thrombus. Right heart insufficiency and hemodynamic markers had a strong correlation with PAD4 and NOX2 levels, indicating that these biomarkers may be employed to assess the severity and prognosis of CTEPH disease and offer a fresh approach to targeted treatment. The results highlight the need for additional study to elucidate platelet-mediated pathways and create therapies for CTEPH that target platelets.

Humans↗

PubMed2025

Impact of Race on Profiles of Platelet Reactivity and Clinical Outcomes in Clopidogrel-Treated Participants.

Black individuals undergoing percutaneous coronary intervention (PCI) experience higher rates of major adverse cardiovascular events (MACE) than non-Black individuals. This study assessed the racial differences in platelet reactivity and clinical outcomes among clopidogrel-treated participants. Two cohorts were analyzed. The pharmacodynamic (PD) cohort involved patients with atherosclerotic cardiovascular disease on maintenance clopidogrel therapy undergoing platelet function testing. The primary outcome was high platelet reactivity (HPR, i.e., P2Y12 reaction unit [PRU] > 208). The PCI cohort included participants undergoing PCI on clopidogrel-based dual antiplatelet therapy. The primary outcome was 1-year MACE, defined as the composite of cardiovascular death, myocardial infarction (MI), ischemic stroke, or stent thrombosis. Data on clinically significant bleeding and CYP2C19 genotyping alleles were collected. The PD and PCI cohorts included 728 (32.1% Black) and 2,770 (20.5% Black) participants, respectively. Black participants had higher PRU levels (184 [IQR 128-234] vs. 144 [IQR 88-195]; P < 0.001) and higher prevalence of HPR (39.3% vs. 20.6%; P < 0.001). Independent predictors of HPR included Black race, hemoglobin levels, and presence of CYP2C19 loss-of-function allele. In the PCI cohort, Black participants had a higher risk of MACE (HR 1.47; 95% CI 1.02-2.11; P = 0.037), primarily driven by MI (HR 1.71; 95% CI 1.09-2.67; P = 0.019), with no significant difference in clinically significant bleeding (HR 1.08; 95% CI 0.65-1.80; P = 0.768). Black participants on clopidogrel exhibit higher platelet reactivity, increased rates of HPR, and an elevated risk of MACE within 1 year after PCI, without significant differences in bleeding compared to non-Black participants.

Aged↗

PubMed2026

The alarmin interleukin-33 modulates platelet proteome, function, and biogenesis.

Platelets, traditionally recognized for their involvement in hemostasis and wound healing, also play a central role in immune regulation and inflammation. Their function and production adapt in response to inflammatory cues such as cytokines and danger-associated molecular patterns. Interleukin-33 (IL-33), an alarmin released during tissue damage, particularly in lung inflammation, has been implicated in influencing platelet biology, though its exact effects remain poorly understood. To clarify IL-33's role, we examined its impact on platelet production, proteome, adhesion, secretion, and aggregation using platelets from IL-33-deficient (IL-33 knockout [IL-33KO]) mice and IL-33 stimulation in vivo. Our results reveal that although platelets themselves do not express IL-33, platelets isolated from IL-33KO mice display altered proteomic signatures and reduced adhesion to fibrinogen, podoplanin, and laminin, alongside impaired thrombus formation under shear stress. IL-33 administration in vivo led to proteomic remodeling characterized by increased expression of inflammatory proteins, as well as changes in platelet morphology, including increased size, typically associated with de novo production. Using lung intravital microscopy, we visualized platelet fragmentation within the lung vasculature in real time, and observed enhanced fragmentation following IL-33 stimulation. Interestingly, ST2, the receptor for IL-33, is expressed in subsets of mouse and human megakaryocytes and hematopoietic progenitors, particularly those involved in a noncanonical pathway of thrombopoiesis that enables the rapid replenishment of platelets during inflammation, infection, and aging. Together, these findings identify IL-33 as a pivotal regulator of platelet function and production, linking inflammatory signaling to the dynamic regulation of thrombopoiesis.

Interleukin-33↗

PubMed2026

Glycolysis-dependent reactive oxygen species mediate desmopressin acetate-induced rescue of platelet dysfunction caused by antiplatelet therapy.

Antiplatelet therapy is extensively used in the prevention and treatment of cardiovascular and cerebrovascular diseases; however, life-threatening hemorrhage requires urgent reversal of platelet dysfunction. Desmopressin acetate has been proposed as a rescue strategy, yet its efficacy and underlying mechanisms remain incompletely understood, particularly regarding redox regulation. A mouse carotid artery blood flow injury model was employed to evaluate the effects of desmopressin acetate on platelet and coagulation dysfunction induced by antiplatelet therapy. Proteomic analyses were performed in both patients and mice to identify differentially expressed proteins. Genetic knockout and pharmacological inhibition approaches were used to investigate the mechanistic pathways involved. Desmopressin acetate effectively restored platelet function and coagulation capacity in antiplatelet-treated mice. Proteomic profiling identified peroxiredoxin-5, a key antioxidant enzyme, as significantly upregulated following antiplatelet therapy but markedly downregulated after desmopressin acetate administration; these findings were validated in plasma samples from 10 patients who received dual antiplatelet therapy for unruptured intracranial aneurysms. Functional studies demonstrated that proteomic profiling identified peroxiredoxin-5 supplementation impaired platelet function, whereas proteomic profiling identified peroxiredoxin-5 knockout or inhibition significantly improved platelet activity. Notably, desmopressin acetate primarily suppressed liver-derived proteomic profiling identified peroxiredoxin-5 expression. Mechanistically, desmopressin acetate enhanced platelet glycolysis via phosphofructokinase-2/fructose-2,6-bisphosphatase 3 activation, leading to increased intracellular reactive oxygen species levels. Inhibition of phosphofructokinase-2/fructose-2,6-bisphosphatase 3 attenuated glycolysis, reduced reactive oxygen species generation, and restored proteomic profiling identified peroxiredoxin-5 expression, thereby abolishing the platelet-rescuing effects of desmopressin acetate. Desmopressin acetate rescued platelet dysfunction induced by antiplatelet therapy through a glycolysis-reactive oxygen species-proteomic profiling identified peroxiredoxin-5 axis, in which glycolysis-driven reactive oxygen species generation plays a central regulatory role. These findings indicate redox modulation as a critical mechanism underlying desmopressin acetate-mediated platelet rescue and suggest a potential therapeutic strategy for managing severe bleeding associated with antiplatelet therapy.

Animals↗

PubMed2026

Ultrashort vs Standard-Duration Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND: The efficacy and safety of ultrashort (≤1-month) dual antiplatelet therapy (DAPT) followed by antiplatelet monotherapy remain uncertain in acute coronary syndrome (ACS) patients. OBJECTIVES: This study sought to compare ultrashort vs standard-duration DAPT in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials until February 15, 2026. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), major bleeding, and net adverse clinical event (NACE). Prespecified subgroup analyses examined by ethnicity (East Asian vs non-East Asian) and abbreviation strategy (intensive: ≤1-week DAPT or clopidogrel/aspirin monotherapy vs moderate: ≥2-week DAPT, followed by ticagrelor/prasugrel monotherapy). RESULTS: Across 10 trials (n = 29,232), ultrashort DAPT did not increase MACCE risk (HR: 1.06; 95% CI: 0.93-1.20; P = 0.38; I2 = 24%), with higher MACCE risk observed in ST-segment elevation myocardial infarction (STEMI) but not non-ST-segment elevation ACS (NSTE-ACS), and significantly reduced major bleeding (HR: 0.47; 95% CI: 0.35-0.64; P < 0.00001; I2 = 44%), resulting in a net clinical benefit (HR: 0.83; 95% CI: 0.72-0.97; P = 0.02; I2 = 61%). Bleeding reduction was more pronounced in East Asians (HR: 0.35; 95% CI: 0.25-0.49; P < 0.00001; I2 = 0%) than non-East Asians (HR: 0.63; 95% CI: 0.43-0.93; P = 0.02; I2 = 44%), with a significant interaction (P = 0.02). The abbreviation strategy significantly modified outcomes (P for interaction = 0.003): intensive abbreviation raised MACCE risk (HR: 1.37; 95% CI: 1.11-1.69; P = 0.003; I2 = 0%), while moderate abbreviation had no statistically significant difference (HR: 0.96; 95% CI: 0.85-1.08; P = 0.47; I2 = 0%). CONCLUSIONS: In patients with ACS undergoing PCI, ultrashort DAPT reduced bleeding without increasing ischemic events overall, although a signal of increased MACCE was observed in STEMI but not in NSTE-ACS. Bleeding reduction was greater in East Asians, while ≤1-week DAPT or clopidogrel/aspirin monotherapy may increase ischemic risk.

Humans↗

PubMed2026

Short-term safety of dual versus single antiplatelet therapy in flow diversion for distal intracranial aneurysms: results from the DART trial.

BACKGROUND AND PURPOSE: Flow diverters (FDs) have become one of the primary treatments for intracranial aneurysms (IAs). However, their use in distal IA has been associated with higher complication rates compared with other techniques. The development of coated FDs, in combination with novel antiplatelet regimens, offers promising strategies to improve the safety profile of FDs in this context. This trial aimed to compare mono antiplatelet therapy (MAPT) using prasugrel versus dual antiplatelet therapy (DAPT) with aspirin and prasugrel for the treatment of distal IA using the p48 MW HPC FD (WallabyPhenox). METHODS: This was a multicenter, prospective, parallel-group, single-blind, non-inferiority randomized trial. Between February 2021 and February 2025, 140 patients were enrolled. After excluding 11 patients, 129 were included in the final analysis. The primary endpoint was the absence of new neurological deficits, defined as no shift in the modified Rankin Scale (mRS) score. The secondary endpoint was the incidence of any stroke. RESULTS: At the 30-day follow-up, 66 patients (98.5%) in the MAPT group and 59 patients (95.2%) in the DAPT group showed no new neurological deficits. With a predefined non-inferiority margin of 5%, the difference of 3.35% confirmed the non-inferiority of MAPT compared with DAPT (p=0.002). The incidence of any stroke was 4/67 (5.9%) in the MAPT group and 6/62 (9.6%) in the DAPT group (p=0.431). CONCLUSION: Prasugrel monotherapy for the treatment of distal IAs using the p48 MW HPC was non-inferior to DAPT within the first 30 days following treatment. CLINICAL TRIAL REGISTRATION: https://ensaiosclinicos.gov.br/rg/RBR-3q9zb73. UTN code: U1111-1290-2489. Research Ethics Committee of the Hospital das Clínicas de Ribeirão Preto - Universidade de São Paulo. CAAE number: 29848720.0.1001.5440.

Humans↗

PubMed2018

Long non-coding RNA metallothionein 1 pseudogene 3 promotes p2y12 expression by sponging miR-126 to activate platelet in diabetic animal model.

Platelet hyperaggregation and hypercoagulation are associated with increase of thrombogenic risk, especially in patients with type 2 diabetes (T2D). High activity of P2Y12 receptor is found in T2D patients, exposing such patients to a prothrombotic condition. P2Y12 is a promising target for antiplatelet, but due to P2Y12 receptor constitutive activation, the clinical practical phenomena such as "clopidogrel resistance" are commonly occurring. In this study, we investigate the role of lncRNA on platelet activation. By lncRNA array, we screened thousands of differentially expressed lncRNA in megakaryocytes from T2D patients and confirmed that lncRNA metallothionein 1 pseudogene 3 (MT1P3) was significantly upregulated in megakaryocytes from T2D patients than in healthy controls. And we further investigate the biofunction of MT1P3 on platelet activation and the regulatory mechanism on p2y12. MT1P3 was positively correlated with p2y12 mRNA levels and promoted p2y12 expression by sponging miR-126. Knockdown of MT1P3 by siRNA reduced p2y12 expression, inhibiting platelet activation and aggregation in diabetes animal model. In conclusion, our findings identify MT1P3 as a key regulator in platelet activation by increasing p2y12 expression through sponging miR-126 under T2D condition. These findings may provide a new insight for managing platelet hyperactivity-related diseases.

Animals↗

PubMed2026

Clopidogrel vs Aspirin According to Diabetes Mellitus: A Prespecified Analysis of the SMART-CHOICE 3 Trial.

BACKGROUND: Recent trials support the superior efficacy of clopidogrel compared to aspirin monotherapy after completion of dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI). However, limited evidence is available in patients with diabetes mellitus (DM). OBJECTIVES: This study sought to evaluate the comparative efficacy and safety of clopidogrel vs aspirin monotherapy according to the presence of DM. METHODS: This was a prespecified analysis of the SMART-CHOICE 3 trial, which was a multicenter, open-label, randomized controlled trial comparing clopidogrel vs aspirin monotherapy in patients with complex coronary lesions or high-risk clinical characteristics. From August 2020 to July 2023, a total of 5,506 patients who underwent PCI and standard DAPT duration and had complex coronary lesions, DM, or previous myocardial infarction, were randomized to clopidogrel or aspirin monotherapy groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite of death from any cause, myocardial infarction, or stroke. RESULTS: Of 5,506 patients, 2,089 had DM (1,039 in the clopidogrel group and 1,050 in the aspirin group). At a median follow-up of 2.3 years (IQR: 1.6-3.0 years), DM patients had a higher risk of MACCE compared to non-DM patients (6.8% vs 4.7%; HR: 1.44, 95% CI: 1.10-1.87; P = 0.008). Clopidogrel showed a significantly lower risk of MACCE than aspirin in DM patients (4.5% vs 9.1%; HR: 0.57, 95% CI: 0.38-0.86; P = 0.008). There was no significant interaction between DM and antiplatelet monotherapy regarding MACCE (P for interaction = 0.124). The risk of bleeding was comparable between the 2 groups in DM patients (2.9% vs 2.9%; HR: 1.06, 95% CI: 0.57-1.95; P = 0.855). CONCLUSIONS: Among DM patients who completed the standard duration of DAPT after PCI, clopidogrel monotherapy was associated with a lower risk of a composite of death from any cause, myocardial infarction, and stroke compared with aspirin monotherapy, without increased rates of bleeding. There was no significant interaction between DM and antiplatelet monotherapy with respect to MACCE. (SMART-CHOICE 3 [SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3]; NCT04418479).

Humans↗

PubMed2026

The effect of zalunfiban on high sensitivity cardiac troponin and the association with clinical outcomes in patients with STEMI.

BACKGROUND: Among individuals with ST-segment elevation myocardial infarction (STEMI), a single subcutaneous injection of the short-acting glycoprotein IIb/IIIa receptor blocker antagonist zalunfiban at first medical contact significantly improved the primary outcome including clinical endpoints. The impact of zalunfiban on Myocardial Infarction (MI) size and association with downstream outcomes remains unclear. METHODS: In a prespecified analysis, we studied results among study participants treated with 2 doses of zalunfiban who had core laboratory measurements concentrations of hs-cTnT. RESULTS: More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation (P = .006) and more frequent Q wave development (P < .001). At coronary angiography more elevated hs-cTnT at presentation was associated with higher thrombus grade and worse epicardial and myocardial perfusion (all P < .05). In multivariable analyses, higher hs-cTnT concentrations at 24 hours were associated with greater adjusted risk for all-cause death (odds ratio [OR] 1.83 per log unit increase; P = .03), cardiovascular death (OR 1.83 per log unit increase; P = .03), heart failure (OR 2.74 per log unit increase; P < .001) or the composite of death and heart failure (P < .001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (P = .04) and across multiples ≥ 10 to ≥ 1,000 times elevation, treatment with zalunfiban resulted in smaller hs-cTnT determined MI size. CONCLUSIONS: Among patients with STEMI, more elevated concentrations of hs-cTnT are associated with worse measures of reperfusion and higher-risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size. TRIAL REGISTRATION: A phase 3 study of zalunfiban in subjects with ST-elevation MI (CELEBRATE); NCT04825743.

Humans↗

PubMed2026

Efficacy and Safety of Rivaroxaban in Patients with Peripheral Artery Disease: A GRADE-assessed Systematic Review and Meta-Analysis.

BACKGROUND: Peripheral artery disease (PAD) is a common atherosclerotic disorder characterized by progressive arterial narrowing in the limbs. This study aims to determine the efficacy and safety of rivaroxaban, focusing on major cardiovascular events, limb outcomes, and bleeding risks. METHODS: PubMed, Cochrane, and EMBASE were searched for randomized controlled trials (RCTs) and nonrandomized comparative studies that compared rivaroxaban, either alone or in combination with aspirin, to placebo or standard care such as antiplatelet therapy. Risk ratios and hazard ratios with 95% confidence intervals were pooled using R v4.5.1 with an appropriate random-effects model applied. Subgroup analyses were performed according to rivaroxaban plus aspirin versus rivaroxaban alone. RESULTS: A total of 39,991 participants across 6 studies were included. Compared with control, use of rivaroxaban was linked to a significant reduction in composite efficacy outcomes (relative risk [RR] = 0.84, 95% confidence interval [CI] 0.78-0.91, P < 0.001), risk of acute limb ischemia (RR = 0.65, 95% CI 0.55-0.78, P < 0.001), and thromboembolism (RR = 0.60, 95% CI 0.38-0.97, P = 0.037). Although rivaroxaban plus aspirin failed to show a significant reduction in the risk of amputation, rivaroxaban alone reported a significant risk reduction (RR = 0.50, 95% CI 0.30-0.85, P = 0.003). However, its use was associated with a significantly higher risk of major bleeding (hazard ratio [HR] = 1.54, 95% CI 1.38-1.72, P < 0.001) and International Society on Thrombosis and Hemostasis-defined bleeding (RR = 1.45, 95% CI 1.19-1.76, P < 0.001). No significant differences were observed for stroke, myocardial infarction, major adverse limb events, fatal bleeding, mortality, or cardiovascular mortality. CONCLUSION: Rivaroxaban-based therapy reduced the trial-defined composite efficacy outcome, acute limb ischemia, and thromboembolism in patients with PAD, but increased the risk of major bleeding. These findings support individualized use of rivaroxaban-based therapy in carefully selected patients, balancing ischemic and limb-protective benefits against bleeding risk.

Humans↗

PubMed2026

Single antiplatelet therapy and tirofiban bridged with surface modified flow diverters for ruptured blood blister-like aneurysms: single center experience and systematic review.

BACKGROUND: Blood blister-like aneurysms (BBAs) of the internal carotid artery are rare but high risk lesions that frequently re-rupture due to their fragile structure and dissecting pathology. Treatment is particularly challenging in ruptured cases, given the risks associated with dual antiplatelet therapy. Recent advancements in flow diverter stents (FDSs) with surface modifications, and the use of single antiplatelet therapy (SAPT), offer a potential alternative strategy. METHODS: We conducted a retrospective review of 17 patients with ruptured internal carotid artery BBAs treated with surface modified FDS under SAPT (ticagrelor or prasugrel) bridged periprocedurally with intravenous tirofiban. All procedures were performed within the acute phase of subarachnoid hemorrhage. Clinical, radiographic outcomes, and procedure related complications were evaluated. RESULTS: Among 17 patients, 94.1% achieved complete angiographic occlusion, and 76.5% attained favorable clinical outcomes (modified Rankin Scale score ≤2). No aneurysm rebleeding or device related ischemic events occurred. A total of 11 patients underwent external ventricular drainage or ventriculoperitoneal shunting without discontinuing SAPT, and no hemorrhagic complications were observed. A literature review incorporating seven additional series identified a total of 42 FDS plus SAPT treated BBA cases, with similar safety and efficacy profiles. CONCLUSIONS: Surface modified FDS with SAPT and tirofiban bridging appears to be a promising treatment option for ruptured BBAs, offering high occlusion rates with minimal thromboembolic and hemorrhagic complications. Larger prospective studies are needed to validate these findings.

Humans↗

PubMed2026

2025 Acute Coronary Syndrome Guideline: Missing the Boat on CYP2C19 Genotyping.

The 2025 American College of Cardiology/American Heart Association/American College of Emergency Physicians/National Association of Emergency Medical Services Physicians/Society for Cardiovascular Angiography & Interventions acute coronary syndrome guideline focuses on strategies to reduce bleeding risk with antiplatelet therapy yet lacks any recommendation related to CYP2C19 genotyping. The impact of CYP2C19 loss-of-function alleles on the effectiveness of clopidogrel is well documented, and although prasugrel and ticagrelor more effectively reduce the risk for atherothrombotic events compared with clopidogrel in patients with a CYP2C19 loss-of-function allele, clopidogrel reduces bleeding risk without an increase in atherothrombotic events compared with prasugrel or ticagrelor in those without a loss-of-function allele. Accordingly, an American Heart Association Scientific Statement supports CYP2C19 genetic testing before oral P2Y12 inhibitors are prescribed. This commentary summarizes the evidence in support of CYP2C19-guided P2Y12 inhibitor selection in the context of other 2025 acute coronary syndrome guideline recommendations and urges future guidelines to incorporate recommendations for CYP2C19 genotyping, especially for those at high bleeding risk.

Humans↗

PubMed2026

Clopidogrel Versus Dual-Antiplatelet Therapy for Long-Term Maintenance After Coronary Stenting in Ischemic and Bleeding Birisk Patients With Acute Coronary Syndromes and Diabetes: A Prespecified Subgroup Analysis of the OPT-BIRISK Trial.

BACKGROUND: Among patients with acute coronary syndromes at both high bleeding and ischemic risk (birisk), extended clopidogrel monotherapy after 9 to 12 months of dual-antiplatelet therapy reduces bleeding without increasing ischemia. Whether this benefit extends to birisk patients with diabetes is unknown. METHODS: This prespecified subgroup analysis of the OPT-BIRISK (Optimal Antiplatelet Therapy for High Bleeding and Ischemic Risk Patients) trial included birisk patients with acute coronary syndrome who had completed 9 to 12 months of dual-antiplatelet therapy after percutaneous coronary intervention. Patients were then randomized 1:1 to 9 months of clopidogrel plus placebo versus clopidogrel plus aspirin. Outcomes were compared by diabetes status. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events, defined as a composite outcome of all-cause death, myocardial infarction, stroke, or clinically driven revascularization. RESULTS: Of 7758 patients, 4072 (52.5%) had diabetes. Clopidogrel monotherapy decreased Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (2.1% versus 3.2%; hazard ratio [HR], 0.66 [95% CI, 0.45-0.97]) with no increase in major adverse cardiac and cerebral events (2.9% versus 3.6%; HR, 0.79 [95% CI, 0.56-1.12]) compared with clopidogrel plus aspirin in patients with diabetes. Outcomes were consistent in patients without diabetes, with no significant interactions by diabetes status. CONCLUSIONS: In birisk patients with acute coronary syndrome who were stable on dual-antiplatelet therapy with clopidogrel plus aspirin for 9 to 12 months after percutaneous coronary intervention, clopidogrel monotherapy for an additional 9 months reduced clinically relevant bleeding without increasing ischemic events compared with continued dual-antiplatelet therapy, irrespective of diabetes status. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03431142.

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