Nakamura K, Yamashita Y, Morimoto T
… +22 more, Muraoka N, Umetsu M, Nishimoto Y, Takada T, Ogihara Y, Nishikawa T, Ikeda N, Otsui K, Sueta D, Tsubata Y, Shoji M, Shikama A, Hosoi Y, Tanabe Y, Chatani R, Tsukahara K, Nakanishi N, Kim K, Ikeda S, Ono K, Kimura T, ONCO DVT Study Investigators
The ONCO DVT study demonstrated the benefit of extended anticoagulation therapy with edoxaban in patients with cancer-associated isolated distal deep vein thrombosis (DVT). However, it remains unclear whether these resul...The ONCO DVT study demonstrated the benefit of extended anticoagulation therapy with edoxaban in patients with cancer-associated isolated distal deep vein thrombosis (DVT). However, it remains unclear whether these results can be applied regardless of the number of thrombosed venous segments. In this post-hoc subgroup analysis of the ONCO DVT study, 601 patients were stratified into the single-site (N=268) and multiple-sites (N=333) DVT subgroups based on the number of thrombosed venous segments at diagnosis. We compared 12-month and 3-month edoxaban treatment groups in each subgroup for the primary endpoint of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death and the major secondary endpoint of major bleeding at 12 months. The cumulative 12-month incidence of the primary endpoint was significantly lower in the 12-month edoxaban group than in the 3-month edoxaban group both in the single-site (0.8% vs. 8.8%, log-rank P=0.007) and in the multiple-sites DVT subgroups (1.4% vs. 8.2%, log-rank P=0.008) without treatment-by-subgroup interaction (P for interaction=0.69). There was no significant difference in the cumulative 12-month incidence of the major secondary endpoint between the 12-month and 3-month edoxaban groups either in the single-site (10.1% vs. 5.0%, log-rank P=0.14) or in the multiple-sites DVT subgroups (10.3% vs. 10.0%, log-rank P=0.98) without treatment-by-subgroup interaction (P for interaction=0.25). In patients with cancer-associated isolated distal DVT, 12-month edoxaban treatment compared to 3-month edoxaban treatment significantly reduced thrombotic events without increasing bleeding risk, suggesting the potential benefit of extended anticoagulation therapy irrespective of the number of thrombosed venous segments at diagnosis.
Mannan MS, Khan MW, Khan MAH
… +3 more, Javed A, Hussain SM, Ahmad W
J Thromb Thrombolysis
· 2026 Jun · PMID 42050242
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UNLABELLED: Age-related proliferation of indeterminate capacity hematopoietic stem and progenitor cells bearing somatic mutations, mainly in DNMT3A, TET2, and ASXL1, is referred to as clonal hematopoiesis of indeterminat...UNLABELLED: Age-related proliferation of indeterminate capacity hematopoietic stem and progenitor cells bearing somatic mutations, mainly in DNMT3A, TET2, and ASXL1, is referred to as clonal hematopoiesis of indeterminate potential (CHIP). In addition to the well-known premalignant effects, CHIP causes systemic effects and predisposes to cardiovascular disease, thromboembolism, and dysfunction of multiple organs. Mutant neutrophils have been increasingly recognized as contributors to this pathology. These cells exhibit aberrant phenotypes and epigenetic alterations associated with pro-inflammatory and pro-thrombotic phenotypes that may favor NET formation. Uncontrolled NETosis may promote endothelial damage, platelet aggregation, and microvascular thrombosis that creates a vicious loop of thromboinflammation. The association of CHIP-related NETosis with venous and arterial thromboses, ischemic stroke, myocardial infarction, and organ-specific damage has been reported, although the main contribution is largely referred from indirect biomarker-based evidence or extrapolation from related conditions. Instead of detecting NET production directly, several studies employ indirect NET markers (such as MPO-DNA, citH3, and cfDNA). Activation of PAD4, generation of reactive oxygen species and inflammatory cytokines are the main modulators implicated in mechanistic studies. Clinically, therapies against NETs using DNase, PAD4, or cytokine blockade have the potential to reduce the risk of thromboinflammation. Although supported by compelling preclinical and observational evidence, there are still challenges because of the use of retrospective studies, murine models, and indirect measure of NET.The current evidence base consists primary of preclinical (murine and in vitro) studies along with observational human data. Future studies are required on prospective trials, mutation-directed biomarkers, and precision medicine modalities to regulate mutant neutrophil functions. Insight into NET-mediated pathogenesis in CHIP does not just clarify the pathways between clonal hematopoiesis and thromboinflammation and dysfunction in the body but also provides opportunities to formulate specific solutions to decrease cardiovascular and systemic illnesses in victims. GRAPHICAL ABSTRACT: [Image: see text]
Spontaneous intracerebral hemorrhage (ICH) accounts for about 10% of strokes in the United States and is linked to high mortality and morbidity. Hematoma expansion independently predicts poor outcomes. Thromboelastograph...Spontaneous intracerebral hemorrhage (ICH) accounts for about 10% of strokes in the United States and is linked to high mortality and morbidity. Hematoma expansion independently predicts poor outcomes. Thromboelastography with platelet mapping (TEG-PM) has shown predictive value for hematoma expansion in traumatic ICH, but its role in spontaneous ICH is unclear. This retrospective cohort study assessed the predictive value of TEG-PM, focusing on arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition, for hematoma expansion in spontaneous ICH patients. Patients with ICH who received TEG-PM and an initial CT scan within 6 h of hospital presentation between January 2018 and April 2024 were included. Hematoma volume was calculated using the ABC/2 method. Hematoma expansion was defined as a relative growth of more than 33% or an absolute increase greater than 6 mL from initial CT. The primary outcome was the predictive value of TEG-PM findings on hematoma expansion. Among 117 patients (median age 62 years; 61.5% male), hematoma expansion occurred in 19 (16.2%). TEG-PM parameters—AA% (6.0% vs. 9.9%; p = 0.37) and ADP% inhibition (16.1% vs. 21.0%; p = 0.77)—did not differ significantly between those with and without expansion. Use of hemostatic agents like desmopressin (12.0%) and tranexamic acid (18.8%) was similar. In-hospital mortality occurred in 17.1%, with no significant difference by expansion status (21.1% vs. 16.3%; p = 0.62). TEG-PM parameters did not predict hematoma expansion in this cohort. The low expansion rate may have limited the predictive value of TEG-PM. These results suggest limited utility of TEG-PM to guide management in spontaneous ICH patients without overt platelet dysfunction or anticoagulation.
In patients on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI), clopidogrel is currently the preferred antiplatelet agent to be given in double antithrombotic therapy (DAT). To explore whet...In patients on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI), clopidogrel is currently the preferred antiplatelet agent to be given in double antithrombotic therapy (DAT). To explore whether aspirin could be an alternative option, a post-hoc analysis of the Italian, multi-center, prospective PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) registry was performed. Out of the 989 patients included in the analysis, 769 (78%) received clopidogrel and 220 (22%) aspirin. Baseline characteristics were largely comparable between the two groups, particularly as regards the indications for PCI and OAC, with acute coronary syndrome and atrial fibrillation respectively, being the most common, the number of stents implanted, and the use of direct oral anticoagulants and proton-pump inhibitors. At a median follow-up of 12.3 months, the primary outcome of net adverse cardiac events (NACE), including major adverse cardiac/cerebral events (MACCE) and major and clinically relevant bleeding was similar with clopidogrel-based and aspirin-based DAT (16.3% vs. 14.6%; p = 0.541). Secondary outcomes of MACCE, all-cause death, cardiac death, non-fatal myocardial infarction, stent thrombosis, non-fatal stroke/transient ischemic attack, target vessel revascularization, and major and clinically relevant bleeding were also comparable. Multivariable analyses confirmed no association between type of DAT and outcomes. Survival analyses showed overlapping event rates between clopidogrel-based and aspirin-based DAT. In patients on OAC undergoing PCI, no significant difference in the occurrence of NACE was observed between clopidogrel-based and aspirin-based DAT. While waiting for further randomized data, individualized physician’s choice may be considered on an individual basis.
Complement factor H (CFH), a key regulatory protein, has demonstrated antithrombotic properties in experimental models. However, the association between circulating CFH levels and the clinical prognosis of deep vein thro...Complement factor H (CFH), a key regulatory protein, has demonstrated antithrombotic properties in experimental models. However, the association between circulating CFH levels and the clinical prognosis of deep vein thrombosis (DVT), particularly the risk of recurrence, remains unexplored in human studies. To investigate the association between baseline serum CFH levels and the long-term risk of recurrent DVT. In this prospective cohort study, patients with a first-time DVT were consecutively enrolled between January 2019 and April 2024. Baseline serum CFH levels were quantified by ELISA, with blood samples collected at hospital admission for the first DVT and prior to the initiation of anticoagulation therapy. High CFH was defined as ≥ 2517.22 ng/mL. Patients were followed for up to five years for objectively confirmed DVT recurrence. The association between CFH levels and DVT recurrence risk was analyzed using cumulative incidence function (CIF) curves, competing risk regression model (Fine-Gray model, with death treated as a competing event), and receiver operating characteristic (ROC) analysis. This study consecutively enrolled 237 patients with DVT. Over a median follow-up of 48 months (IQR, 6.5–60), 23 patients (9.7%) experienced recurrence. Patients with high baseline complement factor H (CFH) levels (≥ 2517.22 ng/mL) had a significantly lower cumulative incidence of recurrence than those with low levels, after accounting for the competing risk of death (Gray’s test, P = 0.013). In Fine-Gray competing risk models, high CFH remained an independent protective factor against recurrence after multivariable adjustment (subdistribution hazard ratio [sHR] = 0.37, 95% CI: 0.16–0.84, P = 0.018). Each unit increase in log-transformed CFH was also associated with reduced risk (sHR = 0.43, 95% CI: 0.23–0.78, P = 0.006). The area under the ROC curve for CFH was 0.688, with a 10-fold cross-validated estimate of 0.630. Our findings suggest an inverse association between higher baseline serum CFH levels and the risk of DVT recurrence, indicating its potential as a candidate biomarker for risk stratification that warrants further validation.
Carotid artery stenosis (CAS) is a major cerebrovascular disease and a leading cause of cerebral ischemic events (CIEs). However, the early identification of CAS patients at high risk of progressing to CIEs remains a sig...Carotid artery stenosis (CAS) is a major cerebrovascular disease and a leading cause of cerebral ischemic events (CIEs). However, the early identification of CAS patients at high risk of progressing to CIEs remains a significant clinical challenge. MicroRNAs, particularly miR-221-3p, have gained research focus for their roles in various pathologies. To evaluate the diagnostic value of miR-221-3p in CAS and elucidate its functional mechanisms. This study enrolled 90 CAS patients and 75 hypertensive controls. Serum miR-221-3p levels were measured by qRT-PCR. Its diagnostic and predictive value was assessed using ROC, logistic regression, and Cox analyses. Cellular effects were evaluated using an ox-LDL-induced human aortic endothelial cells (HAECs) injury model. The miR-221-3p and MYBL1 interaction was verified by luciferase reporter assay, followed by rescue experiments. miR-221-3p levels exhibited a significant upregulation in serum of CAS patients (P < 0.001) and served as an independent risk factor for hypertension patients progressing to CAS (OR = 7.489). It exhibited strong diagnostic value for CAS (AUC = 0.837). Additionally, the positive association between miR-221-3p upregulation and CAS severity (P < 0.001). miR-221-3p was a risk factor for CIEs among CAS patients (HR = 6.421). Functional experiments revealed that inhibiting miR-221-3p reversed ox-LDL-induced damage in HAECs. The direct targeting of MYBL1 by miR-221-3p was verified via the dual-luciferase reporter system. The protective effect of down-regulating miR-221-3p on ox-LDL-induced HAECs injury was significantly reversed by si-MYBL1. Elevated expression of miR-221-3p was observed in CAS and could function as a potential biomarker. miR-221-3p exacerbates ox-LDL-induced injury in HAECs by targeting MYBL1.
Leitinger EJ, Ratnayake N, Taylor S
… +12 more, Yuen HLA, Singh J, Keragala C, Htun K, Ling N, Wilson K, Duncan T, Kaplan Z, Sheppard M, Brown S, Chunilal S, Nalpantidis A
Anticoagulants are high-risk medications associated with significant morbidity and mortality when used inappropriately. Electronic medical records, laboratory results, and medication data can be combined into electronic...Anticoagulants are high-risk medications associated with significant morbidity and mortality when used inappropriately. Electronic medical records, laboratory results, and medication data can be combined into electronic “dashboards”, providing a novel way to screen patients prescribed anticoagulants for potential errors. To describe and evaluate the impact of an efficient electronic dashboard within an Anticoagulation Stewardship service able to identify and facilitate proactive intervention for at-risk patients prescribed anticoagulants. Retrospective audit of adult inpatients receiving anticoagulants between 8th November 2022 and 31st January 2024 in a large multicentre tertiary hospital network. The dashboard was used daily to screen all hospital inpatients prescribed anticoagulants. Prescribing errors and bleeding risk factors were identified, and recommendations were made to treating teams. Cases were subclassified as “high-risk” or “standard-risk” based on the prescribing error and likelihood of harm. Combined clinically relevant non major bleeding (CRNMB) and major bleeding (MB) at 30 days post-intervention. Approximately 10,500 prescribing events were screened, 718 (6.9%) requiring a change to therapy in 611 patients. Of these patients, 292 (48%) were sub-classified as “high-risk”, and the remainder were “standard-risk” (n = 319, 52%). “High-risk” patients demonstrated higher rates of MB/CRNMB compared to those deemed “standard-risk” (7.2% vs. 3.1%, p = 0.022). This real-time dashboard enables rapid screening and identification of inpatients at risk of anticoagulant-related bleeding, allowing for timely intervention to reduce harm.
Sattar Z, Hamza M, Mir J
… +13 more, Rab AU, Shaikh S, Ishaq SM, Upreti P, Upadhyaya A, Awad A, Burhan M, Sattar F, Gonuguntla K, Daggubati R, Sattar Y, Chadi Alraies M, Akram Kawsara M
Percutaneous coronary angiography remains the gold standard for diagnosing and guiding treatment of epicardial coronary artery disease. However, whether adjunctive optical coherence tomography (OCT) improves clinical out...Percutaneous coronary angiography remains the gold standard for diagnosing and guiding treatment of epicardial coronary artery disease. However, whether adjunctive optical coherence tomography (OCT) improves clinical outcomes compared with angiography-guided percutaneous coronary intervention (PCI) remains uncertain. We performed a PRISMA-compliant systematic review and meta-analysis of randomized controlled trials comparing OCT-guided versus angiography-guided PCI. Cardiovascular mortality and stent thrombosis were the primary endpoints. Secondary endpoints included major adverse cardiovascular events (MACE), all-cause mortality, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and minimal stent area (MSA). Ten randomized trials enrolling 6,472 patients were included (3,235 OCT-guided; 3,237 angiography-guided). OCT-guided PCI was associated with significant reductions in cardiovascular mortality (RR 0.54; 95% CI 0.33–0.89; p = 0.01), trial-defined MACE (RR 0.76; 95% CI 0.65–0.89; p < 0.01), and stent thrombosis (RR 0.53; 95% CI 0.33–0.87; p = 0.01). No significant differences were observed in minimal stent area (SMD 0.59; 95% CI − 0.19 to 1.37; p = 0.13), all-cause mortality (RR 0.73; 95% CI 0.52–1.04; p = 0.07), MI (RR 0.82; 95% CI 0.66–1.02; p = 0.07), TVR (RR 0.71; 95% CI 0.30–1.70; p = 0.44), or TLR (RR 0.73; 95% CI 0.43–1.24; p = 0.24). OCT-guided PCI is associated with reductions in trial-defined MACE and cardiovascular mortality, potentially mediated by lower stent thrombosis rates, without significant differences in MSA, all-cause mortality, new onset MI, TVR, or TLR. MSA, all-cause mortality, new onset MI, TVR, or TLR.
Spina E, Spiezia AL, Pia FD
… +12 more, de Mase A, Maurea C, Servillo G, Aramini S, Ranieri A, Barbato S, Cuccurullo C, Tozza S, Esposito A, Andreone V, Manganelli F, Candelaresi P
Intravenous thrombolysis (IVT) is the cornerstone of reperfusion therapy for acute ischemic stroke (AIS), yet only a minority of patients achieve functional independence with vessel re-occlusion in up to one-third of cas...Intravenous thrombolysis (IVT) is the cornerstone of reperfusion therapy for acute ischemic stroke (AIS), yet only a minority of patients achieve functional independence with vessel re-occlusion in up to one-third of cases. IVT targets fibrin but does not inhibit platelet aggregation, providing a rationale for adjunctive early platelet inhibition; so in this context tirofiban, a short-acting glycoprotein IIb/IIIa antagonist, may synergize with thrombolysis, favoring better outcome for AIS patients. We conducted a systematic review and meta-analysis up to August 2025 on MEDLINE (via PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) of RCTs assessing efficacy and safety of early intravenous infusion of tirofiban after thrombolysis in AIS. Outcomes presented as forest plot included functional independence (mRS 0-2), excellent outcome (mRS 0-1), mortality, symptomatic intracranial hemorrhage (sICH), any ICH and early neurological deterioration (END). Risk of Bias was evaluated through Cochrane RoB 2.0 tool. Five RCTs (1,428 patients) were included. At 90 days, functional independence occurred in 78.7% tirofiban-treated versus in 67.8% control patients (RR 1.22, 95% CI 1.05-1.40), with a lower number of END in tirofiban group (RR 0.35, 95% CI 0.15-0.82). Excellent outcome did not significantly differ (RR 2.72, 95% CI 0.26-27.97), as well as mortality (RR 1.07, 95% CI 0.55-2.09), overall ICH rate (RR 1.14, 95% CI 0.75-1.72) and sICH (RR 1.74, 95% CI 0.41-7.42), although an increased number of sICH was observed in tirofiban group. Tirofiban after thrombolysis may be associated with higher rates of functional independence and reduced END. However, given the very low certainty of evidence due to substantial heterogeneity, and imprecision, this meta-analysis should be interpreted as hypothesis-generating, and larger RCTs are required to confirm these findings. PROSPERO: number 1230163.
Acute myocardial infarction (AMI) continues to be a leading cause of global morbidity and mortality, where adverse left ventricular remodeling and subsequent heart failure serve as primary determinants of long-term progn...Acute myocardial infarction (AMI) continues to be a leading cause of global morbidity and mortality, where adverse left ventricular remodeling and subsequent heart failure serve as primary determinants of long-term prognosis. This study aimed to delineate the expression pattern, clinical significance, and molecular mechanisms of miR-4443 in AMI. The study included 100 patients diagnosed with AMI and 100 normal healthy controls. Serum miR-4443 levels were measured by qRT-PCR, and their correlations with patient prognosis were analyzed by Kaplan-Meier curve and Cox regression analysis. To mimic ischemia-reperfusion injury in vitro, human AC16 cardiomyocytes underwent hypoxia/reoxygenation (H/R) treatment. MTT for cell viability, flow cytometry for apoptosis, and ELISA for TNF-α, IL-1β, and IL-6 levels were performed to determine the regulatory role of miR-4443. A bioinformatics analysis predicted the targeting relationship between miR-4443 and TIMP2, and this was validated by the dual-luciferase reporter assay. For matrix remodeling evaluation, MMP2 and MMP9 mRNA expressions were detected by qRT-PCR. The expression of miR-4443 in serum samples from AMI patients was significantly downregulated. The low levels of miR-4443 indicate a poor prognosis for AMI. During H/R injury, miR-4443 expression was downregulated in AC16 cells, its overexpression significantly rescued H/R-induced cell viability decline, increased apoptosis, inflammatory factor release, and upregulation of MMP2/MMP9 expression. TIMP2 was a direct target gene for miR-4443. Functional rescue experiments showed that overexpression of TIMP2 could reverse the protective effect of miR-4443 mimics on H/R injury in cells. Our findings demonstrate that miR-4443 is downregulated in AMI and exerts protective effects against H/R injury in cardiomyocytes, at least in part, through targeting TIMP2, suggesting that the miR-4443/TIMP2 axis may be a potential critical regulatory target in AMI. Further in vivo validation is warranted to substantiate its therapeutic potential.
de Souza DCR, de Oliveira MPR, Sandes PHF
… +7 more, de Oliveira Piñeiro GT, de Vasconcelos GV, Medrado-Nunes GS, Millard FAB, do Nascimento CF, Ogando-Santana V, de Jesus PAP
Thrombolysis beyond the 4.5-h window improves functional outcomes in ischemic stroke. However, no randomized controlled trials (RCTs) have directly compared alteplase and tenecteplase in this extended time frame. To comp...Thrombolysis beyond the 4.5-h window improves functional outcomes in ischemic stroke. However, no randomized controlled trials (RCTs) have directly compared alteplase and tenecteplase in this extended time frame. To compare the efficacy and safety of alteplase versus tenecteplase administered beyond 4.5 h through a network meta-analysis. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched on June 24, 2025. Randomized clinical trials that enrolled adults with acute ischemic stroke treated with alteplase or tenecteplase beyond 4.5 h and reporting at least one primary outcome. PRISMA guidelines for network meta-analyses were applied. Two reviewers independently extracted data and appraised risk of bias. Relative risks (RR) with 95% confidence intervals (CI) were calculated in R Studio (version 2024.12.1 + 563). The primary endpoints were good outcome (modified Rankin Scale [mRS] ≤ 2), and death. Secondary outcome was excellent outcome (mRS 0–1) and any intracranial hemorrhage. A total of 1060 citations were screened; 11 randomized clinical trials were included (n, 2926; age, 69.18 ± 12.63 years; men, 61.65%). Follow-up ranged 90–180 days, with median baseline NIHSS 3–12 and ASPECTS 9–10. No significant differences were found between alteplase and tenecteplase in good outcome (RR, 0.95; 95% CI, 0.84–1.09; P = .41), death (RR, 0.99; 95% CI, 0.60–1.63; P = .95), excellent outcome (RR, 0.95; 95% CI, 0.80–1.12; P = .52), or any intracranial hemorrhage (RR, 0.66; 95% CI, 0.20–2.19; P = .50). In this first network meta-analysis comparing alteplase and tenecteplase beyond 4.5 h, no significant differences in efficacy or safety were observed. Our findings suggest both thrombolytics may be equally viable in late-window stroke, supporting the need for direct RCT comparisons to confirm these results.
The Fontan procedure, the standard palliation for single-ventricle congenital heart disease, is associated with a high burden of thromboembolic complications of unclear etiology. We investigated whether increased circula...The Fontan procedure, the standard palliation for single-ventricle congenital heart disease, is associated with a high burden of thromboembolic complications of unclear etiology. We investigated whether increased circulating lipopolysaccharide (LPS) related to a compromised intestinal barrier is involved in thromboembolic manifestations and markers in the Fontan population. We examined 48 stable adults with Fontan circulation (median age 23 years; range 18-40) and 31 age-matched controls. We assessed serum LPS, and zonulin (marker of increased gut permeability), along with coagulation factors (F; prothrombin, FV, FVII-FX), thrombin generation (prothrombin fragment 1 + 2, thrombin-antithrombin complexes), endogenous anticoagulants (antithrombin, free protein S, tissue factor pathway inhibitor), markers of fibrinolysis (α2-antiplasmin, clot lysis time, plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor), platelet activation (P-selectin, sCD40L), and endothelial injury (von Willebrand factor (vWF), thrombomodulin). Compared with controls, patients with Fontan circulation exhibited higher LPS (+ 207%) and zonulin (+ 125%), which were strongly correlated (r = 0.63; P < 0.001). In the Fontan group, LPS was positively associated with vWF (r = 0.76; P < 0.001), and inversely with free protein S (r = - 0.30; P = 0.04), but not with any other markers. Ten patients (21%) with prior thromboembolic events had higher adjusted (age, sex, BMI) LPS (+ 198%; P < 0.001) and zonulin (+ 147%; P < 0.001) compared with remainder, accompanied by higher vWF (+ 119%), P-selectin (+ 137%), sCD40L (+ 139%), as well as lower FVIII (- 20%) and protein S (- 22%). We are the first to report that patients with Fontan circulation exhibit higher LPS levels related to increased intestinal permeability, which may predispose to thromboembolism and have practical implications.
Optimal antiplatelet therapy after coronary artery bypass grafting (CABG) remains debated. While aspirin is standard, the benefit of adding ticagrelor, a P2Y₁₂ inhibitor with distinct pharmacological properties, is uncle...Optimal antiplatelet therapy after coronary artery bypass grafting (CABG) remains debated. While aspirin is standard, the benefit of adding ticagrelor, a P2Y₁₂ inhibitor with distinct pharmacological properties, is unclear. We compared the efficacy and safety of ticagrelor plus aspirin versus aspirin alone in patients undergoing CABG. We systematically searched major databases for randomized controlled trials and observational studies comparing ticagrelor plus aspirin with aspirin alone in post-CABG patients. The primary efficacy endpoint was trial-defined MACE. Secondary efficacy endpoints included all-cause mortality, cardiovascular death, stroke, MI, revascularization, and saphenous vein graft failure. The primary safety endpoint was major bleeding. A total of seven studies (five randomized controlled trials (RCTs) and one observational study) were included, enrolling 11,893 patients post-CABG, primarily for acute coronary syndrome or stable angina. The majority of studies had a follow-up duration of one year. Ticagrelor plus aspirin significantly reduced the risk of trial-defined MACE (RR 0.61, 95% CI 0.45–0.84; I2 = 0%) and stroke (RR 0.49, 95% CI 0.29–0.82; I2 = 11.5%), but did not reduce all-cause mortality, myocardial infarction, or cardiovascular death. However, it significantly increased the risk of major bleeding (RR 1.70, 95% CI 1.06–2.71; I2 = 42%), while minor bleeding showed no difference (RR 2.38, 95% CI 0.88, 6.43; I2 = 39%). In a sensitivity analysis restricted to RCTs alone (n = 4,905), the reduction in trial-defined MACE remained significant (RR 0.61, 95% CI 0.45–0.84), while the reduction in stroke (RR 0.74, 95% CI 0.35–1.56) and the increase in major bleeding (RR 1.82, 95% CI 0.77–4.34) were no longer statistically significant. In patients undergoing CABG, the addition of ticagrelor to aspirin reduces trial-defined MACE and stroke compared with aspirin alone, but increases the risk of major bleeding without a mortality benefit. These findings support a personalized, risk-stratified approach to antiplatelet therapy, though they are limited by the number and heterogeneity of available studies. Further trials are warranted to define the optimal antiplatelet regimen in this population.Clinical Trial Registration Number: Not applicable.
This study systematically compares the antiplatelet efficacy and safety of indobufen and aspirin based on two key clinical trials, INSURE and OPTION. The INSURE trial showed that in patients with acute moderate-to-severe...This study systematically compares the antiplatelet efficacy and safety of indobufen and aspirin based on two key clinical trials, INSURE and OPTION. The INSURE trial showed that in patients with acute moderate-to-severe ischemic stroke, indobufen was significantly less effective than aspirin in preventing stroke recurrence and did not exhibit superior bleeding safety. In contrast, the OPTION trial indicated that in post-percutaneous coronary intervention patients, indobufen combined with clopidogrel was non-inferior to aspirin combined with clopidogrel in preventing ischemic events and yielded superior net clinical benefit, primarily attributable to a significant reduction in bleeding risk. Analysis of their pharmacological mechanisms suggests these differences may correlate with varying degrees of platelet activation and thrombotic mechanisms under distinct clinical conditions. Subgroup analyses further reveal that comorbidities including diabetes, hypertension, and varying stroke severity may affect therapeutic outcomes, underscoring the value of individualized treatment strategies. In summary, the clinical positioning of indobufen should be tailored to the treatment context and patient characteristics: it is not recommended as a routine alternative to aspirin for secondary prevention of acute ischemic stroke, but it may serve as a potential therapeutic option in coronary artery disease patients at high bleeding risk or intolerant to aspirin supported by limited clinical evidence, rather than a broadly established alternative. Caution is warranted given the absence of supporting evidence from international guidelines and limited regulatory approval in many regions. Future research should further clarify its benefit-risk profile across diverse populations and combination regimens to guide precision therapy.
Alnomani YR, Algazar M, Omar MM
… +5 more, Aldemerdash MA, Henes K, Arafa A, Rageh BM, Abdelaziz A
J Thromb Thrombolysis
· 2026 Jun · PMID 41904366
·
Full text
Transcatheter aortic valve replacement (TAVR) carries risks of vascular and bleeding complications. We aimed to study the effectiveness of Angio-Seal combined with Perclose ProGlide versus dual Perclose ProGlide followin...Transcatheter aortic valve replacement (TAVR) carries risks of vascular and bleeding complications. We aimed to study the effectiveness of Angio-Seal combined with Perclose ProGlide versus dual Perclose ProGlide following transfemoral TAVR. We searched PubMed, Cochrane Library, Scopus, and WOS from inception until November 2024 for studies comparing Parclose ProGlide with Angio-Seal versus dual Parclose ProGlide in transfemoral TAVR. The primary outcome was major vascular complications, while other secondary outcomes were bleeding complications, the need for additional vascular closure device (VCD), minor vascular complications, unplanned surgical intervention, mortality, hematoma, pseudoaneurysm, and dissection. Dichotomous outcomes were pooled and analyzed using odds ratio (OR) with 95% confidence interval (CI) via the DerSimonian-Laird random-effect model. Seven studies (two RCTs and five observational studies) comprising 1,766 patients were included. In RCT-only analyses, single Perclose ProGlide combined with Angio-Seal showed no significant difference compared with dual Perclose ProGlide in major vascular complications (OR = 0.54, 95% CI [0.28-1.04], P = 0.07) or major/life-threatening bleeding (OR = 0.66, 95% CI [0.25-1.74], P = 0.40). However, it significantly reduced the need for additional vascular closure devices (OR = 0.11, 95% CI [0.05-0.24], P < 0.01) and minor vascular complications (OR = 0.52, 95% CI [0.38-0.72], P < 0.01). For dual Perclose ProGlide combined with Angio-Seal, no RCTs were available; observational evidence suggested a reduction in major/life-threatening bleeding compared to dual Perclose ProGlide (OR = 0.43, 95% CI [0.21 to0.92], p = 0.03), while there was no significant difference between the two groups upon excluding Costa et al. (EuroIntervention, 17:728-735, 2021) (OR = 0.56, 95% CI [0.26 to 1.21], p = 0.14). Based on the available RCTs, the combination of single Perclose ProGlide with Angio-Seal during transfemoral TAVR significantly reduces the need for additional vascular closure devices. It may also reduce minor vascular complications, but this effect is not consistently robust. The pooled analysis of observational studies suggests a potential benefit of dual Perclose ProGlide combined with Angio-Seal for major/life-threatening bleeding. However, this finding was not robust in sensitivity analyses and no RCTs have evaluated this strategy.