Use Of Antiplatelet Drugs Research Articles

Assessment of secondary prevention awareness among patients with coronary artery disease: A survey including patients from 3 centers.

In this study, we aimed to investigate the awareness of patients with coronary artery disease (CAD) about secondary prevention and the channels through which they obtained information on this issue. A standard questionnaire including 45 questions was given to the patients (n=912) who were admitted to the cardiology outpatient clinics to investigate their secondary prevention awareness and lifestyle. Of the participants, 508 (55.7%) stated that they knew the condition of their vessels after coronary angiography; 493 (54.1%) stated that they did not exercise; 299 stated that they did not follow any specific diet. Men were more frequently aware of all risk factors except diet, blood glucose, and blood pressure compared to women (p<0.001). Women were more frequently aware that blood glucose and blood pressure are risk factors for CAD compared to men (p<0.001). The high-income patient group was more aware of all the risk factors, except blood glucose compared to the low/medium income patient group (p<0.001). The frequency of awareness, except for blood glucose and antiplatelet drugs, increased as the education level increased (p<0.001). However, the frequency of awareness of blood glucose and antiplatelet drug use was higher in the literate/elementary school/secondary school group (p<0.001). In addition, it was concluded that patients' sexual life and psychological problems after being diagnosed with the disease were rarely questioned by cardiology specialists. Awareness of patients with CAD about secondary prevention was found to be very low.

Differences in oral anticoagulant prescriptions between specialists and non-specialists in patients with cardioembolic stroke caused by non-valvular atrial fibrillation.

Atrial fibrillation (AF) is a common disease encountered in daily practice; however, few patients with AF received oral anticoagulant (OAC) therapy. This study focused on differences in OAC prescriptions and influencing factors between specialists (neurological and cardiovascular) and non-specialists. A retrospective comparative analysis was conducted on 480 patients with acute cardioembolic stroke caused by non-valvular AF who were admitted to our hospital between January 1, 2015, and December 31, 2020. All patients had visited our hospital or other hospitals for their underlying diseases. Overall, 232 (specialist group SG) and 248 patients (non-specialist group NSG) were examined by specialists and non-specialists, respectively. The NSG had a significantly lower percentage of OAC prescriptions on admission than the SG (P < 0.01), even after propensity score matching. Factors influencing OAC prescription in the SG were age, hypertension, paroxysmal AF, dementia, CHADS2 score, and antiplatelet drug use, while those in the NSG were a history of cerebral infarction, paroxysmal AF, dementia, and antiplatelet drug use [SG: age, odds ratio (OR) 0.919, 95% confidence interval (CI) 0.865-0.976; hypertension, OR 0.266, 95% CI 0.099-0.713; paroxysmal AF, OR 0.189, 95% CI 0.055-0.658; dementia, OR 0.253, 95% CI 0.085-0.758; CHADS2 score, OR 2.833, 95% CI 1.682-4.942; and antiplatelet drug use, OR 0.072, 95% CI 0.025-0.206; NSG: cerebral infarction, OR 5.940, 95% CI 1.581-22.309; paroxysmal AF, OR 0.077, 95% CI 0.010-0.623; dementia, OR 0.077, 95% CI 0.014-0.438; and antiplatelet drug use, OR 0.024, 95% CI 0.004-0.152]. In conclusion, the OAC prescription rate was higher in patients with non-valvular AF whose family physicians were specialists at the time of cerebral infarction onset. In addition, in the SG, advanced age and hypertension were associated with not prescribing OAC, whereas a higher CHADS2 score was associated with the prescription of OACs. In the NSG, a history of cerebral infarction was associated with the prescription of OACs. Further, paroxysmal AF, antiplatelet drug use, and dementia were associated with non-OAC therapy in both the groups.

Xuesaitong oral preparation as adjuvant therapy for treating acute cerebral infarction: A systematic review and meta-analysis of randomized controlled trials

Ethnopharmacological relevanceCerebral infarction is the second leading cause of death and the third most common cause of disability. The use of anti-platelet aggregation drugs is prone to bleeding, liver and kidney damage, gastrointestinal reactions, and is not suitable for patients to take for a long time. Xuesaitong oral preparations (XSTOP), a traditional Chinese medicine formula, has shown therapeutic effect on treating cerebral infarction based on the clinical practice and pharmacological mechanism.Aim of the study: The study aims to evaluate the effectiveness and safety of XSTOP combined with conventional treatment (CT) in treatment of acute cerebral infarction (ACI), and to provide the reliable evidence for clinical application. Materials and methodsWe performed a literature search in Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, PubMed, EMBASE, Cochrane Library and Web of Science from their inceptions to August 2021. Systematic searches for randomized controlled trials (RCTs) of XSTOP in treatment of ACI. Odds ratio (OR) or mean difference (MD) with their 95% confidence interval was calculated between with and without XSTOP therapy. Cochrane risk of bias tool was used to evaluate the methodological quality of the included trials. ResultsEight RCTs involving 827 patients were included in this meta-analysis. By comparing XSTOP plus conventional treatment with conventional treatment alone, the meta-analysis gave the following results: (1) Total effective rate (OR = 4.53, 95% CI[2.85, 7.19], P < 0.0001); (2) National Institutes of Health Stroke Scale (NIHSS) score (MD = −3.22, 95% CI[-4.52, −1.92], P＜0.00001); (3) Plasma viscosity (PV) (MD = −0.74, 95%CI [-0.96, −0.51], P＜0.00001), hole blood high-cut viscosity (HBV) (MD = −0.63, 95%CI [-0.73, −0.53], P = 0.84), whole blood low-cut viscosity (LBV) (MD = −0.37, 95%CI [-0.56, −0.19], P = 0.96), fibrinogen (FIB) (MD = −23.78, 95%CI [-28.57, −18.99], P = 1.00), hematocrit (Hct) (MD = −2.76, 95%CI [-3.16, −2.36], P = 0.96); (4) China Stroke Scale (CSS) score (MD = −6.53, 95% CI[-9.07, −3.99], P＜0.00001); (5) No significant adverse reactions were reported; (6) The evidence was downgraded to “very low” quality, according to GRADE system. ConclusionXSTOP plus CT is conditional recommended to improve the total effective rate, NIHSS score, PV, CSS score, and no serious adverse reactions were noted. The GRADE assessment indicates that the overall certainty quality of evidence is very low. Further large-scale, well-designed and high-quality RCTs are needed to confirm the positive results. As all studies included were conducted in China. It is unclear if the findings of this meta-analysis could be generalized to other populations.

Abstract 10919: Prevalence, Awareness, Treatment, and Control of Hypertension in Hospitalized Patients with Atrial Fibrillation in China: Findings from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project

Introduction: Reports on the current status of hypertension control in patients with atrial fibrillation (AF) remain lacking in China. We aimed to provide the latest estimates on the prevalence, awareness, treatment, and control rates of hypertension and factors associated with uncontrolled hypertension in hospitalized patients with AF in China. Methods: Based on the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) Project, hospitalized patients with AF collected from 236 hospitals in 30 provinces of China between February 2015 and December 2019 were included in current analysis. The prevalence, awareness, treatment, and control rates of hypertension were estimated according to the Chinese Hypertension Guideline. Hypertension was defined as SBP ≥140mmHg or DBP ≥90mmHg measured at the time of admission, or a documented history of hypertension. Multivariable logistic regression was used to analyze the factors associated with uncontrolled hypertension (SBP ≥140 mmHg or DBP≥90mmHg). Results: A total of 61,136 hospitalized patients with AF were included, and the prevalence of hypertension was 66.1%. The awareness, treatment, and control rates of hypertension were 80.1%, 55.8%, and 39.9%, respectively. Among patients treated for hypertension, only 46% had their blood pressure controlled. The rates varied by patient characteristics and geographic regions (Table). Younger age (18-45 years of age), rural insurance, alcohol drinking, history of heart failure, mitral stenosis, pre-hospital use of antiplatelet drugs, valvular AF, new-onset AF, and Northeast China were associated with uncontrolled hypertension in patients with AF. Conclusions: Hypertension is common in hospitalized patients with AF. Although most patients are aware of this comorbidity, the treatment and control rates of hypertension are still low. The management of hypertension in patients with AF needs to be further strengthened.

Abstract 10705: Association Between Clinical Outcomes and Bleeding Risk Factors in Very Elderly Patients with Atrial Fibrillation at High Bleeding Risk: The Fushimi Af Registry

Background: The ELDERCARE-AF trial demonstrated that low-dose edoxaban (15 mg once-daily) prevented stroke or systemic embolism (SE) in very elderly Japanese patients with nonvalvular atrial fibrillation (NVAF) who were inappropriate for standard oral anticoagulant therapy due to high bleeding risk. The association between clinical outcomes and bleeding risks in such patients in routine clinical practice are unclear. Methods: From the Fushimi AF registry, we obtained ELDERCARE-eligible patients with NVAF who aged ≥80 years, had CHADS 2 score ≥2, and had one or more bleeding risks as shown in the ELDERCARE-AF trial: low creatinine clearance (15 to 30 ml/min), a history of bleeding from a critical organ, low body weight (≤45 kg), or regular use of antiplatelet drugs. The association of the four bleeding risk factors with the outcomes was evaluated in eligible patients. Results: We obtained 549 ELDERCARE-eligible patients (12.8% of entire cohort, 52.8% of ≥80 years and CHADS 2 score ≥2). The median follow-up period was 1,823 (interquartile range: 809-2,900) days. The incidences (% per patient-year) of stroke/SE, major bleeding, all-cause mortality, and cardiovascular death were significantly higher in eligible patients than in non-eligible patients (stroke/SE: 4.6% vs. 2.0%, major bleeding: 3.5% vs. 1.8%, all-cause mortality: 15.5% vs. 3.9%, cardiovascular death: 2.9% vs. 0.6%, all log-rank P&lt;0.001). Among the four bleeding risk factors, low body weight and low creatinine clearance were significantly associated with the incidence of all-cause mortality (adjusted hazard ratio [95% confidence interval], low body weight: 1.56 [1.16-2.10], P=0.003, low creatinine clearance: 1.70 [1.23-2.25], P&lt;0.001). Low creatinine clearance was also significantly associated with the incidence of cardiovascular death (2.55 [1.35-4.81], P=0.004). However, none of the four bleeding risk factors had associations with the incidences of stroke/SE or major bleeding after multivariate adjustment. Conclusion: Patients with NVAF who met the inclusion criteria of the ELDERCARE-AF trial had poor clinical outcomes, and low creatinine clearance was associated with the incidences of both all-cause and cardiovascular mortality.

Comprehensive Multi-Parameter Characterisation of Circulating Extracellular Vesicles from Rivaroxaban-Treated VTE Patients Reveals Reduced Inflammation and Ameliorated Endothelial Dysfunction

Venous Thromboembolism (VTE) remains a significant cause of morbidity and mortality worldwide. Rivaroxaban, a direct oral factor Xa inhibitor, mediates anti-inflammatory and cardiovascular-protective effects besides its well-established anticoagulant properties, however, these remain poorly characterized. Extracellular vesicles (EVs) are important circulating messengers regulating a myriad of biological and pathological processes and may be highly relevant to the pathophysiology of VTE as they reflect alterations in platelet and endothelial biology. However, the effects of Rivaroxaban on circulating pro-inflammatory EVs in VTE patients remain unknown. We hypothesized that rivaroxaban's anti-inflammatory properties are reflected upon differential molecular profiles of circulating EVs.Single-episode VTE patients anticoagulated with 20 mg Rivaroxaban or warfarin at a target INR of 2.0-3.0, respectively, who had commenced therapy no sooner than 3 months previously were recruited following informed written consent at the Mater Misericordiae University Hospital, Dublin, Ireland. Patient data including age, sex, BMI, prevalent risk factors and comorbidities were collected. Patients on warfarin therapy had a time in therapeutic range of at least 55% and an INR in target range at time of blood sampling. Exclusion criteria included known pro-inflammatory conditions, active malignancy, recurrent VTE, antiphospholipid syndrome, bleeding or platelet function disorders, use of anti-platelet drugs, and thrombocytopenia.To address the hypothesis, we firstly used a combination of Nanoparticle Tracking Analysis (NTA) and flow cytometry to comprehensively characterise differences in the concentration and size of small (0-200 nm) and large (200-1000 nm) circulating EVs, respectively. Statistical analysis revealed a trend towards reduced levels of circulating small and large EVs in Rivaroxaban-treated VTE patients compared with matched warfarin controls. Moreover, small and large EVs measured in the patients plasma correlated strongly and highly significantly (r=0.804, p<0.0001), indicating a concomitant decrease in both populations. As circulating EVs are considered pro-coagulant and pro-inflammatory, these results may point towards an ameliorated baseline pro-inflammatory state of VTE patients anticoagulated with Rivaroxaban. To further uncover Rivaroxaban-mediated alterations, we next compared proteomic profiles of circulating EVs. We robustly quantified over 300 vesicular proteins. Statistical analysis of the protein expression level using a student's t-test with a false discovery rate of 5% and a minimal fold change of 0.1 identified differential protein expression of a tightly regulated cluster of proteins involved in negative feedback regulation of inflammatory and coagulation pathways in Rivaroxaban-treated patients, which may in part contribute to the superior outcomes of Rivaroxaban-treated patients seen in recent clinical trials. Furthermore, we recently established that Rivaroxaban potentially ameliorates endothelial dysfunction in a cohort of non-valvular atrial fibrillation patients. Therefore, we aimed to also assess circulating markers of endothelial activation (Intercellular Adhesion Molecule 1 [ICAM-1] and Tissue Factor Pathway Inhibitor [TFPI]). Intriguingly, Rivaroxaban-treated patients exhibited an increase in plasma TFPI levels with a simultaneous decrease in soluble ICAM-1, potentially pointing towards ameliorated endothelial dysfunction in Rivaroxaban-treated VTE patients relative to warfarin.Collectively, we established that EV proteomic signatures are powerful biological sensors of Rivaroxaban's anti-inflammatory potential. Moreover, Rivaroxaban therapy may ameliorate endothelial dysfunction relative to warfarin. These findings are of translational relevance towards characterizing the anti-inflammatory and cardiovascular-protective mechanisms associated with Rivaroxaban therapy. DisclosuresKevane: Leo Pharma: Research Funding. Murphy: Bayer Pharma: Research Funding. Ni Ainle: Daiichi-Sankyo: Research Funding; Actelion: Research Funding; Leo Pharma: Research Funding; Bayer Pharma: Research Funding. Maguire: Bayer Pharma: Research Funding; Actelion: Research Funding.

Microbial Fibrinolytic Enzymes as Anti-Thrombotics: Production, Characterisation and Prodigious Biopharmaceutical Applications.

Cardiac disorders such as acute myocardial infarction, embolism and stroke are primarily attributed to excessive fibrin accumulation in the blood vessels, usually consequential in thrombosis. Numerous methodologies including the use of anti-coagulants, anti-platelet drugs, surgical operations and fibrinolytic enzymes are employed for the dissolution of fibrin clots and hence ameliorate thrombosis. Microbial fibrinolytic enzymes have attracted much more attention in the management of cardiovascular disorders than typical anti-thrombotic strategies because of the undesirable after-effects and high expense of the latter. Fibrinolytic enzymes such as plasminogen activators and plasmin-like proteins hydrolyse thrombi with high efficacy with no significant after-effects and can be cost effectively produced on a large scale with a short generation time. However, the hunt for novel fibrinolytic enzymes necessitates complex purification stages, physiochemical and structural-functional attributes, which provide an insight into their mechanism of action. Besides, strain improvement and molecular technologies such as cloning, overexpression and the construction of genetically modified strains for the enhanced production of fibrinolytic enzymes significantly improve their thrombolytic potential. In addition, the unconventional applicability of some fibrinolytic enzymes paves their way for protein hydrolysis in addition to fibrin/thrombi, blood pressure regulation, anti-microbials, detergent additives for blood stain removal, preventing dental caries, anti-inflammatory and mucolytic expectorant agents. Therefore, this review article encompasses the production, biochemical/structure-function properties, thrombolytic potential and other surplus applications of microbial fibrinolytic enzymes.

Ciddi Epistaksis olan Hastalarda Rutin Koagülasyon Teslerinin Değerlendirmesi

Aim: There are studies about coagulation parameters are not required in the management of epistaxis. The aim of the present study was to investigate whether or not coagulation tests are required and its relationship with medications in severe epistaxis cases that require intervention. Material and Method: The patients above 16 years who had presented to emergency department due to epistaxis, who had undergone anterior/posterior nasal packing or electro-cautery to the nasal mucosa were included the study. The demographic characteristics, blood count, coagulation test, anti-platelet and anti-coagulant medications, the procedures carried out for stopping bleeding, whether reversal treatment or blood transfusion was needed were recorded. Results: A total of 469 patients, it was found that coagulation parameters had been tested in 141(30.2%). While PT, aPTT and INR values of the anti-coagulant using patients were significantly higher(p&amp;lt;0.001, p=0.003, p&amp;lt;0.001, respectively), the platelet and hemoglobin values were not found to be associated with anti-platelet drug and anti-coagulant use(p=0.304, p=0.098, respectively). The patients were allocated to two groups as those any parameter of whom was impaired or not. While a significant difference was found between the groups with regard to hemoglobin values(p=0.006), no patients were determined to need reversal treatment or hemoglobin replacement.Conclusion: Routine coagulation testing is not required for patients who have epistaxis that cannot be stopped with conservative methods and who are using anti-platelet drugs as it does not lead to a difference in treatment. Coagulation tests may not be performed in patients who use anti-coagulants based on the results.

Complement factor D is linked to platelet activation in human and rodent sepsis

BackgroundThe complement factor D (CFD) exerts a regulatory role during infection. However, its physiological function in coagulopathy and its impact on the course of an infection remains unclear.MaterialsWild-type and CFD-deficient mice (n = 91) were subjected to cecal ligation and puncture to induce sepsis. At several time points, markers of coagulation and the host-immune response were determined. Furthermore, in patients (n = 79) with sepsis or SIRS, CFD levels were related to clinical characteristics, use of antiplatelet drugs and outcome.ResultsSeptic CFD-deficient mice displayed higher TAT complexes (p = 0.02), impaired maximal clot firmness, but no relevant platelet drop and reduced GPIIb/IIIa surface expression on platelets (p = 0.03) compared to septic wild-type mice. In humans, higher CFD levels (non-survivors, 5.0 µg/ml to survivors, 3.6 µg/ml; p = 0.015) were associated with organ failure (SOFA score: r = 0.33; p = 0.003) and mortality (75% percentile, 61.1% to 25% percentile, 26.3%). CFD level was lower in patients with antiplatelet drugs (4.5–5.3 µg/ml) than in patients without.ConclusionIn mice, CFD is linked to pronounced platelet activation, depicted by higher GPIIb/IIIa surface expression in wild-type mice. This might be of clinical importance since high CFD plasma concentrations were also associated with increased mortality in sepsis patients.

Evaluation of acute and chronic nephrotoxicity in patients received cisplatin-based chemotherapy: has anything changed over time?

The aim of this study was to determine the frequency and the risk factors of acute and chronic nephrotoxicity in patients who received cisplatin due to malignancy. Medical records of all patients who received cisplatin-based chemotherapy regimen between January 2013 and July 2019 were retrospectively evaluated. The data of 203 patients who met the study criteria were examined. The patients were evaluated for acute nephrotoxicity at 48h and late nephrotoxicity at 3rd month after first course of cisplatin. Early and late nephrotoxicity were defined by NCI CTCAE Version 4.0 criteria. The mean age of the study patients was 56.44 ± 12.69years, 78.8% were males and 21.2% were females. It is revealed that the incidence of cisplatin-induced acute nephrotoxicity was 9.2% and chronic nephrotoxicity was 37.9%. While the development of acute nephrotoxicity was associatedwith female gender, history of diabetes mellitus, history of ischemic heart disease and use of antiplatelet drug, the development of chronic nephrotoxicity was associatedwith older age, female gender and using of diuretics. High serum creatinine, urea and low eGFR value before treatment were found to be associated with both early and late nephrotoxicity (p < 0.05). There was no statistically significant relationship between acute or chronic nephrotoxicity and cumulative dose of cisplatin, hydration or intravenous magnesium supplementation. High initial serum creatinine value and low initial eGFR are the most important determinants of both early and late nephrotoxicity.

Antiplatelet therapy in patients with conservatively managed spontaneous coronary artery dissection from the multicentre DISCO registry.

The role of antiplatelet therapy in patients with spontaneous coronary artery dissection (SCAD) undergoing initial conservative management is still a matter of debate, with theoretical arguments in favour and against its use. The aims of this article are to assess the use of antiplatelet drugs in medically treated SCAD patients and to investigate the relationship between single (SAPT) and dual (DAPT) antiplatelet regimens and 1-year patient outcomes. We investigated the 1-year outcome of patients with SCAD managed with initial conservative treatment included in the DIssezioni Spontanee COronariche (DISCO) multicentre international registry. Patients were divided into two groups according to SAPT or DAPT prescription. Primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction (MI), and any unplanned percutaneous coronary intervention (PCI). Out of 314 patients included in the DISCO registry, we investigated 199 patients in whom SCAD was managed conservatively. Most patients were female (89%), presented with acute coronary syndrome (92%) and mean age was 52.3 ± 9.3 years. Sixty-seven (33.7%) were given SAPT whereas 132 (66.3%) with DAPT. Aspirin plus either clopidogrel or ticagrelor were prescribed in 62.9% and 36.4% of DAPT patients, respectively. Overall, a 14.6% MACE rate was observed at 12 months of follow-up. Patients treated with DAPT had a significantly higher MACE rate than those with SAPT [18.9% vs. 6.0% hazard ratios (HR) 2.62; 95% confidence intervals (CI) 1.22-5.61; P = 0.013], driven by an early excess of non-fatal MI or unplanned PCI. At multiple regression analysis, type 2a SCAD (OR: 3.69; 95% CI 1.41-9.61; P = 0.007) and DAPT regimen (OR: 4.54; 95% CI 1.31-14.28; P = 0.016) resulted independently associated with a higher risk of 12-month MACE. In this European registry, most patients with SCAD undergoing initial conservative management received DAPT. Yet, at 1-year follow-up, DAPT, as compared with SAPT, was independently associated with a higher rate of adverse cardiovascular events (ClinicalTrial.gov id: NCT04415762).

Clinical history and gastrointestinal bleeding in patients taking oral anticoagulants

BackgroundCommon risk factors for gastrointestinal bleeding (GIB) are advanced age and the use of antiplatelet or anticoagulants drugs for the prevention of cardiovascular diseases. MethodsIn this prospective real-world observational study, oral anticoagulated patients were recruited and followed between June 2013 and December 2019. The primary end-point was to evaluate a possible relationship between bleeding events and patients' clinical history of gastrointestinal disease prior to the start of the therapy. The secondary end-points were time of GIB appearance and the percentage of idiopathic or provoked events, i.e., bleeding due to a gastrointestinal disease. In case of GIB event all the patients were studied by means of endoscopic procedures. Cox regression was used to calculate the relative hazard ratios (HRs) of GIB for each considered clinical variable. Results734 patients on both VKAs or DOACs were studied. Overall, 46 hemorrhagic events were recorded: 6 were major bleeding (0.42/100 patient-years) while 43 were clinically relevant non major bleeding (2.8/100 patient-years). The Cox regression analysis did not show any relationships among GIB and the variables considered. ConclusionThe patients' clinical history is neither a predictor for GIB bleeding nor a guide to the choice of the oral anticoagulant to be administered. Routinely applying bleeding risk screening, such as occult blood in the stool, should be added to the periodic laboratory checks for early recognition of patients at higher risk of GIB.

Clinical characteristics and outcomes of chronic subdural hematoma in patients with a history of antiplatelet therapy

ObjectiveChronic subdural hematoma (CSDH) is a common neurosurgical disease. Many patients with CSDH take antiplatelet (AP) drugs. Several studies have focused merely on the relationship between AP drug use and recurrence without deeply analyzing the specific clinical features of these patients. The primary objective of this study was to investigate the detailed clinical characteristics and outcomes of CSDH patients with a history of AP therapy. MethodsA total of 1181 CSDH patients over 40 years of age who received burr-hole craniostomy were enrolled. Clinical information, computed tomographic findings, and data on long-term outcomes and recurrence among these patients were gathered. We divided these patients into two groups according to whether they had a history of AP therapy. Percentages and χ2 tests were applied for categorical variables. Standard deviations and 2-sided unpaired t-tests were applied for continuous variables. Univariate and multivariate logistic regression analyses were performed to identify independent factors of the outcomes (6 months after discharge). ResultsAP therapy was not related to the outcomes of patients with CSDH (P = 0.48), and there were no differences in recurrence between the AP and non-AP group. Only Bender grade (P < 0.01, B = −3.14, Exp (B) = 0.04, 95% CI 0.01–0.29) was associated with the outcomes of patients in the AP group. The incidence of complications in the AP group was higher than that in the non-AP group (P < 0.01). Postoperative thrombotic events may be more likely to occur in the AP group than in the non-AP group (P = 0.02). Patients in the AP group were older (P < 0.01) and had more comorbidities (P < 0.01). ConclusionsPatients treated with AP therapy had more complications. The outcomes of patients treated with AP therapy were associated with their status of admission. Patients treated with AP therapy were at greater risk for postoperative thrombotic events. The recurrence rate of CSDH did not appear to be affected by AP therapy.

New Trends and Advances in Non-Variceal Gastrointestinal Bleeding-Series II.

The gastrointestinal tract is a long tubular structure wherein any point in the mucosa along its entire length could be the source of a hemorrhage. Upper (esophagel and gastroduodenal) and lower (jejunum, ileum, and colon) gastrointestinal bleeding are common. Gastroduodenal and colonic bleeding are more frequent than bleeding from the small bowel, but nowadays the entire gastrointestinal tract can be explored endoscopically and bleeding lesions can be locally treated successfully to stop or prevent further bleeding. The extensive use of antiplatelet and anticoagulants drugs in cardiovascular patients is, at least in part, the cause of the increasing number of patients suffering from gastrointestinal bleeding. Patients with these conditions are usually older and more fragile because of their comorbidities. The correct management of antithrombotic drugs in cases of gastrointestinal bleeding is essential for a successful outcome for patients. The influence of the microbiome in the pathogenesis of small bowel bleeding is an example of the new data that are emerging as potential therapeutic target for bleeding prevention. This text summarizes the latest research and advances in all forms of acute gastrointestinal bleeding (i.e., upper, small bowel and lower). Diagnosis is approached, and medical, endoscopic or antithrombotic management are discussed in the text in an accessible and comprehensible way.

Platelet P2Y12 Receptor Deletion or Pharmacological Inhibition does not Protect Mice from Sepsis or Septic Shock

Introduction Platelets are increasingly appreciated as key effectors during sepsis, raising the question of the usefulness of antiplatelet drugs to treat patients with sepsis. Objective Evaluate the potential contribution of the platelet P2Y 12 receptor in the pathogenesis of polymicrobial-induced sepsis and septic shock in mice. Methods The effects of P2Y 12 inhibition using clopidogrel treatment and of platelet-specific deletion of the P2Y 12 receptor in mice were examined in two severity grades of cecal ligation and puncture (CLP) leading to mild sepsis or septic shock. Results Twenty hours after induction of the high grade CLP, clopidogrel- and vehicle-treated mice displayed a similar 30% decrease in mean arterial blood pressure (MAP) characteristic of shock. Septic shock-induced thrombocytopenia was not modified by clopidogrel treatment. Plasma concentrations of inflammatory cytokines and myeloperoxidase (MPO) were similarly increased in clopidogrel- and vehicle-treated mice, indicating comparable increase in systemic inflammation. Thrombin-antithrombin (TAT) complexes and the extent of organ damage were also similar. In mild-grade CLP, clopidogrel- and vehicle-treated mice did not display a significant decrease in MAP, while thrombocytopenia and plasma concentrations of TNFα, IL6, IL10, MPO, TAT and organ damage reached similar levels in both groups, although lower than those reached in the high grade CLP. Similarly, mice with platelet-specific deletion of the P2Y 12 receptor were not protected from CLP-induced sepsis or septic shock. Conclusion The platelet P2Y 12 receptor does not contribute to the pathogenesis of sepsis or septic shock in mice, suggesting that P2Y 12 receptor antagonists may not be beneficial in patients with sepsis or septic shock.

Cardiovascular Interventions in Patients with Hemophilia and Severe Von Willebrand Disease.

The management of cardiovascular interventions in patients with hemophilia and severe von Willebrand disease (VWD) is challenging. The procedure itself as well as the use of anti-platelet drugs and anticoagulants implies a risk of bleeding. On the other hand, factor replacement therapy as well as withdrawal of anti-platelet drugs or anticoagulants may increase the risk of cardiovascular events and thrombosis. Information on the management of such interventions is limited to very few case reports. Here, we report a retrospective analysis of 28 patients with hemophilia A (n=16), hemophilia B (n=4) or VWD (n=8, all with VWF:RCo <30 IU/dl), who underwent a total of 39 cardiovascular interventions including coronary angiography (CA, n=11), percutaneous coronary interventions (PCI, n=18), or cardiac surgery (CS, n=10) including coronary artery bypass grafting (CABG) and heart valve surgery with the use of cardiopulmonary bypass (CPB). Patients had a median age of 66 years (range 47–85) and had a median factor activity of 3 IU/dl (range <1–35). Six patients were on regular prophylaxis prior to the intervention. Patients undergoing CA received replacement therapy for a median of 2 days (range 1–15) with a median starting dose of 36 IU/kg (range 24–67). Minor bleeding at the site of puncture occurred in 5 of 11 patients. Major bleeding or bleeding requiring transfusion did not occur. Patients undergoing PCI received replacement therapy for a median of 4 days (range 1–41) with a starting dose of 40 IU/kg (range 12–63) given before or during the intervention. 12 of 14 patients receiving bare metal stents were on aspirin and clopidogrel for 4 to 6 weeks; 7 of these including all patients with severe hemophilia received prophylactic replacement therapy for the time of dual anti-platelet therapy. Two patients received shorter courses of single anti-platelet agents due to bleeding. Three patients receiving drug-eluting stents were on aspirin and clopidogrel for 8 to 12 weeks; 2 of these also received prophylactic replacement therapy, whereas one patient with mild hemophilia did not. Minor bleeding at the site of puncture occurred in 15 of 18 patients undergoing PCI; major bleeding at the site of puncture occurred in 1 patient and required transfusion. Major bleeding at distant sites occurred in 3 patients with 1 patient requiring transfusion. Two of these three patients received anti-platelet therapy without prophylactic factor replacement. No patient experienced stent thrombosis or other thromboembolic complications. Patients undergoing cardiac surgery received replacement therapy for a median of 23 days (range 11–46) with a median starting dose of 57 IU/kg (range 23–107). Unfractionated heparin was used for anticoagulation during CPB. Minor wound bleeding occurred in 8 of 10 patients. Four patients received transfusions of 2 to 5 units of packed red blood cells. Five of seven patients undergoing CABG received aspirin. One patient with VWD undergoing CABG and biological aortic valve replacement received oral anticoagulation and experienced gross hematuria; he was switched to aspirin after 6 weeks. A patient with mild hemophilia on long-term oral anticoagulation because of atrial fibrillation remained on oral anticoagulants without signs of bleeding. In summary, this is the largest cohort of patients with hemophilia and severe VWD undergoing cardiovascular interventions. Combining replacement therapy with anti-platelet agents or anticoagulants appears to be a safe strategy, despite of frequent minor bleeding. Major bleeding mainly occurred in patients on anti-platelet agents without concomitant prophylactic replacement therapy.

Staged Endovascular Treatment for Symptomatic Occlusion Originating From the Intracranial Vertebral Arteries in the Early Non-acute Stage.

Background: The ideal treatment for patients who survive from acute vertebrobasilar artery occlusion but develop aggressive ischemic events despite maximal medical therapy in the early non-acute stage is unknown. This paper reports the technical feasibility and outcome of staged endovascular treatment in a series of such patients with symptomatic intracranial vertebral artery occlusion.Methods: Ten consecutive patients who presented with aggressive ischemic events in the early non-acute stage of intracranial vertebral artery occlusion from Jan 2015 to Nov 2020 were retrospectively reviewed. Among them, eight male and two female patients with a mean age of 66.7 years developed aggressive ischemic events, and the NIHSS score was elevated by a median of 7 points despite medical therapy. All patients received staged endovascular treatment 4–21 days from onset, at an average of 11 days. The strategy of staged treatment was as follows: first, a microwire was passed through the portion of the occlusion, which was then dilated with balloon inflation to maintain the perfusion above TICI grade 2b. Then, with the use of antiplatelet drugs, the residual intravascular thrombus was gradually eliminated by the continuous perfusion and an activated fibrinolytic system, leaving the residual stenosis. A second stage of angioplasty with stent implantation was subsequently performed if residual stenosis was ≥50%. The NIHSS scores and mRS scores were compared between pre- and post-endovascular treatment groups and in the follow-up period.Results: Technical success was achieved in 9 patients who received staged endovascular treatment (perforation occurred in one patient during the first stage). The NIHSS scores were significantly improved, with a median score 7 points lower on discharge compared with the scores for the most severe status. Favorable outcomes with mRS score ≤ 2 were achieved in 7 and 9 patients at the 3-month follow-up and the latest follow-up, respectively, which was better than the preoperative status.Conclusion: Staged endovascular treatment might be a safe, efficient, and viable option in carefully selected patients with symptomatic intracranial vertebral artery occlusion in the early non-acute stage. However, this needs to be confirmed by further investigation, preferably in a large, controlled setting.

Glycoprotein IIb/IIIa Inhibitors May Modulate the Clinical Benefit of Radial Access as Compared to Femoral Access in Primary Percutaneous Coronary Intervention: A Meta-Regression and Meta-Analysis of Randomized Trials.

Objectives Several randomized controlled trials (RCTs) consistently reported better clinical outcomes with radial as compared to femoral access for primary percutaneous coronary intervention (PCI). Nevertheless, heterogeneous use of potent antiplatelet drugs, such as Gp IIb/IIIa inhibitors (GPI), across different studies could have biased the results in favor of radial access. We performed an updated meta-analysis and meta-regression of RCTs in order to appraise whether the use of GPI had an impact on pooled estimates of clinical outcomes according to vascular access. Methods We computed pooled estimates by the random-effects model for the following outcomes: mortality, major adverse cardiovascular events (death, myocardial infarction, stroke, and target vessel revascularization), and major bleedings. Additionally, we performed meta-regression analysis to investigate the impact of GPI use on pooled estimates of clinical outcomes. Results We analyzed 14 randomized controlled trials and 11090 patients who were treated by radial (5497) and femoral access (5593), respectively. Radial access was associated with better outcomes for mortality (risk difference 0.01 (0.00, 0.01), p=0.03), MACE (risk difference 0.01 (0.00, 0.02), p=0.003), and major bleedings (risk difference 0.01 (0.00, 0.02), p=0.02). At meta-regression, we observed a significant correlation of mortality with both GPI use (p=0.011) and year of publication (p=0.0073), whereas no correlation was observed with major bleedings. Conclusions In this meta-analysis, the use of radial access for primary PCI was associated with better clinical outcomes as compared to femoral access. However, the effect size on mortality was modulated by GPI rate, with greater benefit of radial access in studies with larger use of these drugs.

Antiplatelet therapy and future intracerebral hemorrhage in hemodialysis patients with cerebral microbleeds

The use of antiplatelet drugs is thought to increase the risk for intracerebral hemorrhage (ICH) in patients with cerebral microbleeds (CMBs). However, hemodialysis (HD) patients have a high prevalence of CMBs and diverse pathologies that require antiplatelet therapy. In this study, we investigated whether the use of antiplatelet drugs increases the risk for ICH in HD patients with CMBs. Brain magnetic resonance imaging (MRI), including T2*-weighted MRI, was performed in 179 HD patients with no history of cerebrovascular events. CMBs were detected and patients were followed prospectively with a median follow-up period of 5.2 [1.4–6.2] years. To investigate whether the influence of antiplatelet therapy on the development of ICH differs in cases with and without CMBs, the inverse probability of treatment weighting method was used, including an interaction term between the presence or absence of CMBs and use of antiplatelet drugs. As a result, CMBs were detected in 45 patients (25.1%), and antiplatelet drugs were used in 66 patients (36.9%). When the effect of antiplatelet therapy on the incidence of ICH was modified by the presence of CMBs at baseline (P for interaction <0.001), the use of antiplatelet drugs was a significant risk factor for ICH in HD patients without CMBs, but not in HD patients with CMBs. Furthermore, the burden of CMBs significantly increased the risk for ICH, but the increase in this risk was slower in antiplatelet drug users as compared to non-antiplatelet drug users (P for interaction = 0.02). The influence of antiplatelet drugs on the development of ICH differed depending on the presence or absence of CMBs. In fact, the use of antiplatelet drugs did not increase the risk for ICH in HD patients with CMBs.

Antiplatelet Medications Are Associated With Bleeding and Decompensation Events Among Patients With Cirrhosis.

In an aging population with cardiovascular comorbidities, anticoagulant (AC), antiplatelet (AP), and nonsteroidal anti-inflammatory drug (NSAID) use are increasing. It remains unclear whether these agents pose increased bleeding risk in cirrhosis. This study aimed to assess the association between these medications and bleeding and portal hypertension complications in cirrhosis. The IMS PharMetrics database was used to identify privately insured adults diagnosed with cirrhosis from 2007 to 2015, stratified as compensated or decompensated based on the presence of portal hypertensive complications 1 year before cirrhosis diagnosis. Bleeding or decompensation outcomes were assessed 6 to 18 months after cirrhosis diagnosis using a landmark analysis design. Multivariable Cox proportional hazards regression modeling assessed associations between AC, AP, and NSAID drug exposures and outcomes adjusting for covariates. A total of 18,070 cirrhosis patients were analyzed; 57% male; 74% ages 50 to 64 years; 34% with a prior decompensation. Overall, 377 (2%) had claims for ACs; 385 (2%) APs; and 1231 (7%) NSAIDs. APs were associated with increased bleeding [adjusted hazard ratio (aHR)=1.31; 95% confidence interval (CI): 1.00, 1.72] and decompensation events (aHR=1.44; 95% CI: 1.06, 1.95) in a 9-month landmark analysis. NSAIDs were significantly associated with bleeding events (aHR=1.29; 95% CI: 1.06, 1.57) on 3-month landmark analysis. No statistically significant associations were seen between ACs and bleeding or decompensation outcomes in adjusted analyses. AP use was associated with increased bleeding and decompensation events among privately insured patients with cirrhosis. NSAID use was associated with significant early bleeding, but not decompensations. Lastly ACs were not associated with bleeding or decompensation outcomes.