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Abstract Background and purpose Although Ginkgo biloba extract (GBE) has been shown to be effective in treating acute ischemic stroke (AIS) in several clinical trials, concerns regarding adverse events, such as bleeding, have been raised. This study aimed to investigate the mechanisms by which GBE improves AIS prognosis, particularly its impact on platelet activity, coagulation function, and the potential risk of bleeding. Methods This real-world study consecutively enrolled 99 patients: 49 with internal jugular venous stenosis (IJVS) treated with GBE; 33 with AIS treated with GBE and low-dose aspirin; and 17 with AIS treated with low-dose aspirin alone. Plasma platelet aggregation and coagulation status were assessed before and after treatment. Major and minor bleeding events were recorded in the AIS group. Results In the IJVS group, GBE specifically inhibited arachidonic acid (AA)-induced, but not ADP-induced, platelet aggregation, along with prolonged thrombin time (PT) and activated partial thromboplastin time (APTT). In the AIS group, the combined use of low-dose aspirin and GBE further reduced AA-induced platelet aggregation, mildly prolonged APTT, and was associated with an increased risk of minor bleeding events. Conclusions The therapeutic effect of GBE in AIS may, in part, be attributed to its ability to enhance the antiplatelet action of aspirin, particularly in inhibiting AA-induced platelet aggregation. However, the potential for increased bleeding risk warrants further investigation.

Abstract Background Extracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse. Methods Using the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders. Results Among 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p

Abstract Background Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. Objective The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. Methods An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. Results We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874–7.036, P 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). Conclusion The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

Abstract Background The prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome. Methods We included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS). Results During the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p

Abstract Background In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). Methods The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. Findings The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. Interpretation Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.

Abstract Background Due to limitations associated with clopidogrel following percutaneous coronary intervention (PCI), other newer oral anti-platelet agents are being studied. We aimed to systematically carry out a direct comparison of outcomes observed with prasugrel versus clopidogrel following PCI. Methods Common online searched databases (The Cochrane library, EMBASE, MEDLINE and Google scholar) were used to retrieve relevant publications. Primary endpoints were the adverse cardiovascular outcomes. Secondary outcomes were the bleeding events. This analysis was carried out by RevMan 5.3, whereby odds ratios (OR) and 95% confidence intervals (CI) were considered as the statistical parameters. Results Eight studies with a total number of 18,122 participants were included in this direct analysis. Prasugrel was associated with significantly lower adverse cardiovascular outcomes in comparison to clopidogrel following PCI. All-cause mortality, myocardial infarction, stroke, stent thrombosis and major adverse cardiac events were all significantly lower with prasugrel (OR: 0.47, 95% CI: 0.35–0.63; P = 0.0001), (OR: 0.68, 95% CI: 0.57–0.80; P = 0.00001), (OR: 0.60, 95% CI: 0.38–0.96; P = 0.03), (OR: 0.46, 95% CI: 0.30–0.72; P = 0.0006) and (OR: 0.61, 95% CI: 0.53–0.70; P = 0.00001) respectively. When the bleeding outcomes were analyzed, Thrombolysis in Myocardial Infarction (TIMI) defined major and minor bleeding were not significantly different (OR: 0.91, 95% CI: 0.66–1.27; P = 0.59) and (OR: 1.16, 95% CI: 0.85–1.59; P = 0.35) respectively. However, the combined ‘all bleeding events’ was significantly higher with prasugrel (OR: 1.32, 95% CI: 1.03–1.70; P = 0.03), but when patients with STEMI and those undergoing elective PCI were separately analyzed, no significant difference in overall bleeding was observed. Conclusion Adverse cardiovascular outcomes were significantly lower with the use of prasugrel in comparison to clopidogrel following PCI. In addition, TIMI defined major and minor bleeding were not significantly different showing prasugrel to be well-tolerated following PCI especially in patients with acute coronary syndrome.