Antiplatelet Research Articles

Evaluating Receipt of Optimal Medical Therapy Among Structurally Disadvantaged Groups Undergoing Amputation

Optimal medical therapy (OMT) for peripheral artery disease (PAD) is associated with decreased major amputation and mortality. OMT has several components, including antiplatelet and high-intensity statin therapy, blood pressure control, etc. While there are disparities in receipt of OMT among PAD patients, it is unknown if patients from disadvantaged neighborhoods, measured by the area deprivation index (ADI), are less likely to be on OMT. We performed a retrospective review of patients that underwent major lower extremity amputation between 2015 and 2019 at two large academic healthcare systems. Primary exposure was high ADI, defined as ADI ≥60th percentile, and secondary exposure was non-Hispanic Black (NHB) race. For each analysis, the primary outcome of interest was receipt of OMT, defined here as at least one antiplatelet agent and a high-intensity statin. The exposure outcome relationship was assessed using multivariable logistic regression. Among 354 patients with median age of 66 (interquartile range [IQR] 58-74), 267 (75.4%) were male, 219 (61.9%) identified as NHB and 116 (32.8%) as non-Hispanic White. Overall, 91 (25.7%) patients were on OMT at time of amputation despite 57.3% of the cohort being established with a vascular surgeon. Compared to those with low ADI, the category high ADI had a higher proportion of NHB patients (48.1% vs 70.3%, p= 0.001) and patients were more often hospitalized at the University-affiliated facilities (47.4% vs 63.0%, p= 0.004). High ADI was not associated with receipt of OMT prior to major amputation (adjusted odds ratio [aOR] 0.72, 95% confidence interval [CI] 0.42-1.24). In secondary analysis, NHB race was not associated with receipt of OMT. Stratification by facility type (Veterans Affairs and University-affiliated facilities) also showed no association between high ADI or race and receipt of OMT. Neighborhood economic well-being is not associated with receipt of OMT prior to major amputation. While the absence of socioeconomic disparities is notable, the proportion of patients on OMT is suboptimal. Care processes should be critically evaluated and quality measures potentially created to improve the rate of receipt of OMT among patients at risk for amputation.

Efficacy and safety of aspirin in venous thromboembolism prevention after total hip arthroplasty, total knee arthroplasty or fracture.

Background: This study aims to analyse the efficacy and safety of aspirin in the prevention of venous thromboembolism (VTE) for patients undergoing total hip arthroplasty (THA), total knee arthroplasty (TKA) or fracture. Patients and methods: Two independent investigators searched PubMed, Embase, Cochrane and ClinicalTrials.gov from January 2000 to June 2023 to retrieve randomized control trials (RCTs) about aspirin in VTE prevention after arthroplasty or fracture. Then, the relative risk (RR) was utilized to evaluate its efficiency and safety. Results: A total of 16 RCTs with 27,864 patients were included. There was no statistical difference in the incidence of deep-vein thrombosis (RR: 1.31, p = 0.100), pulmonary embolism (RR:1.05, p = 0.850), VTE (RR:1.28, p = 0.290), major bleeding (RR:0.96, p = 0.900), and death (RR:1.01, p = 0.960) between the aspirin group and the anticoagulants group. Subgroup analysis showed that a relatively higher incidence of deep-vein thrombosis in patients undergoing TKA (RR:1.49, p = 0.030), fracture (RR:1.48, p = 0.001), patients receiving 81 mg aspirin twice daily (RR:1.48, p = 0.001) and patients from North America (RR:1.57, p<0.001) when comparing aspirin with anticoagulants. Meanwhile, the incidence of VTE was higher in patients receiving 100 mg aspirin once daily (RR:1.82, p<0.001) compared with anticoagulants. Additionally, the incidence of all bleeding (RR:2.00, p = 0.030) was higher in patients receiving aspirin in Asia compared with anticoagulants. Conclusions: In terms of clinical effectiveness and safety, aspirin (antiplatelet agent) was generally not inferior to anticoagulants in the prevention of VTE after THA, TKA, or fracture. Notably, the clinical effectiveness of aspirin was affected by different surgical types, the doses of aspirin and races.

Clinical and cost-effectiveness of clopidogrel resistance genotype testing after ischaemic stroke or transient ischaemic attack: a systematic review and economic model.

Stroke or transient ischaemic attack patients are at increased risk of secondary vascular events. Antiplatelet medications, most commonly clopidogrel, are prescribed to reduce this risk. Factors including CYP2C19 genetic variants can hinder clopidogrel metabolism. Laboratory-based or point-of-care tests can detect these variants, enabling targeted treatment. To assess the effectiveness of genetic testing to identify clopidogrel resistance in people with ischaemic stroke or transient ischaemic attack. Specific objectives: Do people tested for clopidogrel resistance, and treated accordingly, have a reduced risk of secondary vascular events? Do people with loss-of-function alleles associated with clopidogrel resistance have a reduced risk of secondary vascular events if treated with alternative interventions compared to clopidogrel? Do people with loss-of-function alleles associated with clopidogrel resistance have an increased risk of secondary vascular events when treated with clopidogrel? What is the accuracy of point-of-care tests for detecting variants associated with clopidogrel resistance? What is the technical performance and cost of CYP2C19 genetic tests? Is genetic testing for clopidogrel resistance cost-effective compared with no testing? Systematic review and economic model. Objective 1: Two studies assessed secondary vascular events in patients tested for loss-of-function alleles and treated accordingly. They found a reduced risk, but confidence intervals were wide (hazard ratio 0.50, 95% confidence interval 0.09 to 2.74 and hazard ratio 0.53, 95% confidence interval 0.24 to 1.18). Objective 2: Seven randomised controlled trials compared clopidogrel with alternative treatment in people with genetic variants. Ticagrelor was associated with a lower risk of secondary vascular events than clopidogrel (summary hazard ratio 0.76, 95% confidence interval 0.65 to 0.90; two studies). Objective 3: Twenty-five studies compared outcomes in people with and without genetic variants treated with clopidogrel. People with genetic variants were at an increased risk of secondary vascular events (hazard ratio 1.72, 95% confidence interval 1.43 to 2.08; 18 studies). There was no difference in bleeding risk (hazard ratio 0.98, 95% confidence interval 0.68 to 1.40; five studies). Objective 4: Eleven studies evaluated Genomadix Cube accuracy; no studies evaluated Genedrive. Summary sensitivity and specificity against laboratory reference standards were both 100% (95% confidence interval 94% to 100% and 99% to 100%). Objective 5: Seventeen studies evaluated technical performance of point-of-care tests. Test failure rate ranged from 0.4% to 19% for Genomadix Cube. A survey of 8/10 genomic laboratory hubs revealed variation in preferred technologies for testing, and cost per test ranging from £15 to £250. Most laboratories expected test failure rate to be < 1%. Additional resources could enhance testing capacity and expedite turnaround times. Objective 6: Laboratory and point-of-care CYP2C19 testing strategies were cost-saving and increase quality-adjusted life-years compared with no testing. Both strategies gave similar costs, quality-adjusted life-years and expected net monetary benefit. Our results suggest that CYP2C19 testing followed by tailored treatment is likely to be effective and cost-effective in both populations. Accuracy and technical performance of Genedrive. Test failure rate of Genomadix Cube in a NationalHealthServicesetting. Value of testing additional loss-of-function alleles. Appropriateness of treatment dichotomy based on loss-of-function alleles. Lack of data on Genedrive. No randomised 'test-and-treat' studies of dipyramidole plus aspirin. This study is registered as PROSPERO CRD42022357661. This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135620) and is published in full in Health Technology Assessment; Vol. 28, No. 57. See the NIHR Funding and Awards website for further award information.

Role of L-carnitine in Cardiovascular Health: Literature Review.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Secondary preventive measures, like anti-platelet medications, B-blockers, and angiotensin-converting enzyme (ACE) inhibitors, have been found to dramatically lower the risk of cardiovascular disease. However, prolonged usage of these drugs has been linked to multiple adverse impacts. Hence, finding more efficient treatments, especially dietary strategies for long-term use in daily life, is advantageous for primary prevention and treatment. L-carnitine, a naturally occurring amino acid derivative normally synthesized in the liver and kidney, is believed to have a considerable influence on cardiovascular health. L-carnitine can enhance both contractile performance and structural integrity of the cardiac muscle by maintaining efficient energy production and reducing oxidative stress. This literature review aims to address several pressing questions regarding the role of L-carnitine in cardiovascular health: what are the physiological functions of L-carnitine, particularly in relation to cardiovascular health; how effective and safe is L-carnitine supplementation in the management of various cardiovascular diseases, primarily ischemic heart disease, heart failure, and peripheral vascular disease; what are the underlying mechanisms through which L-carnitine exerts its cardioprotective effects; what controversies exist in the current research; and finally, what should be the future directions? Through this comprehensive analysis, the review aims to enrich our understanding of L-carnitine's role in cardiovascular health, providing a robust foundation for future academic and clinical endeavors. PubMed, Embase, and Google Scholar have been used to search the following keywords: L-carnitine, cardiovascular health, mitochondrial function, and L-carnitine side effects. Then, using the existing search engine formats, some keyword combinations were used to find the related articles included and every possibility, including using every first keyword combination with another keyword, using every keyword in every place at each given box, etc. Around 308 articles were reviewed using this process, including systemic reviews, meta-analysis studies, randomized controlled trials, and literature review articles. Inthe end, after leaving the pure articles related to the topic as 35 articles, which are attached below with direct citation, the majority of them were very fresh articles, as recent as 2010, and back words, except just one paper related to the impact of L-carnitine post-myocardial infarction, as its data provided us with a positive and promising impact of L-carnitine in this field. L‑carnitine seems to have a pivotal role in cardiovascular health due to its energy metabolism, anti-oxidative stress, and endothelial role. The safety and effectiveness of L-carnitine administration remain an issue for scientific investigation. One of the major concerns is that the intestinal metabolism of L-carnitine generates trimethylamine-N-oxide (TMAO), a compound that has been linked with faster atherosclerosis progression.

Is initial unilateral revascularization acceptable in pediatric patients with bilateral moyamoya disease with mild contralateral hemodynamic disturbance?

Although asymmetrical vascular involvement between hemispheres is common in pediatric patients with bilateral moyamoya disease, whether hemispheres with mild vascular changes and hemodynamic impairment require immediate surgical revascularization or whether they can be observed until disease progression remains unclear. The authors evaluated the long-term outcomes of their strategy to initially perform unilateral surgery and withhold surgery to the contralateral hemispheres with mild vascular changes and hemodynamic impairment. The authors retrospectively evaluated Japanese pediatric patients (onset age ≤ 15 years) diagnosed with bilateral sporadic moyamoya disease who underwent unilateral revascularization. The authors investigated whether the patient underwent additional collateral surgery and the incidence of ischemic events during follow-up. They also compared visual assessments of arterial spin labeling (ASL) images obtained before initial surgery, before additional contralateral surgery, and at last follow-up. Overall, 30/47 patients (63.8%) experienced progression of hemodynamic impairment in the contralateral hemisphere and underwent additional surgery. The age at initial surgery of the patients who needed additional contralateral surgery was significantly younger than that of the patients who did not require contralateral surgery (mean [SD] 7.0 [3.0] years vs 9.8 [2.6] years, p = 0.002). One patient (age 4 years) developed ischemic stroke before admission for preoperative evaluation 2 months after novel symptom onset, and another patient (age 6 years) experienced ischemic stroke in the contralateral hemisphere while discontinuing antiplatelet agents before surgery; both patients fully recovered from the neurological deficits. In contralateral hemispheres that required additional surgery, the ASL visual assessment scores significantly decreased before the additional contralateral surgery compared to those obtained before the initial surgery (p = 0.008). In pediatric patients with bilateral moyamoya disease, withholding surgery for hemispheres with mild vascular changes and hemodynamic impairment is generally safe. Younger patients were more likely to experience contralateral progression and require additional surgery, so close follow-up is needed. ASL imaging is useful for detecting and following the progression of hemodynamic impairment in conservatively treated hemispheres.

Gastrointestinal Bleeding After Percutaneous Coronary Intervention: Incidence, Risk Factors, and Outcomes.

Percutaneous coronary intervention (PCI) is a well-established method for treating coronary artery disease. However, stent implantation necessitates the use of antiplatelet agents, which increases the risk of gastrointestinal bleeding (GIB). This study aims to assess the incidence, etiology, and outcomes of GIB within one year post-PCI at Sultan Qaboos University Hospital (SQUH), Muscat, Oman. This retrospective analysis included 435 patients who underwent PCI at SQUH between January and December 2017, excluding those with multiple PCI procedures and incomplete data. GIB was defined using the thrombolysis in myocardial infarction (timi) bleeding score. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 23 (IBM Corp., Armonk, NY) with binary logistic regression employed to identify significant risk factors for GIB. A p-value < 0.05 was considered statistically significant. GIB was identified in 15 patients (age 67.8 ± 8.8 years; 60% male), resulting in an incidence within one year post-PCI of 3.4%. Melena (53.3%) and hematemesis (20.0%) were the most frequent clinical presentations, with peptic ulcer disease being the predominant underlying etiology (40%). Significant risk factors included advanced age, chronic kidney disease, pre-existing peptic ulcer disease, and the use of non-steroidal anti-inflammatory drugs. The incidence of GIB observed in this study aligns with previously reported rates. These findings highlight the importance of pre-PCI risk stratification for bleeding, especially in high-risk patients. Prophylactic measures, such as the use of gastric protective agents, should be considered to mitigate the risk of GIB in patients undergoing PCI.

Clopidogrel therapy in nonischemic central retinal vein occlusion: A case report and therapeutic insight

Abstract: Central retinal vein occlusion (CRVO) is a significant cause of vision impairment in adults, often associated with various systemic and ocular risk factors. The current literature presents a limited understanding of the efficacy of antithrombotic agents in CRVO management, with sparse comparative studies evaluating the effectiveness of different antiplatelet therapies. Here, we report the case of nonischemic CRVO in a 54-year-old male with multiple systemic comorbidities, including diabetes mellitus, hypertension, and dyslipidemia. Initial treatment with aspirin 100 mg daily resulted in worsening visual acuity (VA) and retinal pathology, prompting a transition to clopidogrel 75 mg daily due to patient refusal of intravitreal injection. Remarkably, clopidogrel therapy led to rapid and sustained improvement in VA, macular edema resolution, and complete resolution of retinal vascular pathology within weeks. This case underscores the therapeutic potential of clopidogrel in nonischemic CRVO management, suggesting its superiority over aspirin in select patients. We discuss the mechanisms underlying the differential efficacy of antiplatelet agents and highlight the need for further comparative studies to guide optimal treatment strategies in CRVO.

Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease.

Despite consistent recommendations from clinical guidelines, data from randomized trials on a long-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease are still lacking. We conducted a multicenter, open-label, adjudicator-masked, randomized trial comparing edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease (defined as coronary artery disease previously treated with revascularization or managed medically). The risk of stroke was assessed on the basis of the CHA2DS2-VASc score (scores range from 0 to 9, with higher scores indicating a greater risk of stroke). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months. Secondary outcomes included a composite of major ischemic events and the safety outcome of major bleeding or clinically relevant nonmajor bleeding. We assigned 524 patients to the edoxaban monotherapy group and 516 patients to the dual antithrombotic therapy group at 18 sites in South Korea. The mean age of the patients was 72.1 years, 22.9% were women, and the mean CHA2DS2-VASc score was 4.3. At 12 months, a primary-outcome event had occurred in 34 patients (Kaplan-Meier estimate, 6.8%) assigned to edoxaban monotherapy and in 79 patients (16.2%) assigned to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The cumulative incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.7%) in the edoxaban monotherapy group and in 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53). In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy. (Funded by the CardioVascular Research Foundation and others; EPIC-CAD ClinicalTrials.gov number, NCT03718559.).

Evaluation of an Antithrombotic Surface-Coated Flow Diverter in a Rabbit Model without Dual Antiplatelet Drugs

OBJECTIVEFlow diverters (FDs) carry the risk of thromboembolic complications associated with the device and bleeding complications associated with dual antiplatelet therapy. We hypothesize that an antithrombotic surface coated flow diverter(BSCFD) would have less acute thrombus formation and better endothelialization on the device surface compared to uncoated flow diverter. METHODSAn antithrombotic surface coated FD(BSCFD) was developed. Acute clot formation and chronic endothelialization over the device were assessed in 8 rabbit models comparing to its prototype FD(PFD) at 2 hours and 1 month by Scanning Electron Microscopy(SEM) and Histologic images. Nonparametric score data, including thrombus, injury, endothelialization, adventitial inflammation, intramural bleeding and intimal hyperplasia were compared between BSCFD and PFD using Kendall coefficient of rank correlation. RESULTSParent artery and branch artery were patent on DSA in 8 BSCFDs and 6 PFDs. There was 1 intra-stent thrombosis in PFDs at 2 hours and 1 intra-stent stenosis in PFD at 1 month. SEM at 2 hours showed that large amount of blood cells adhered to the surface of all 4 PFDs, and no blood cells were found on the surface of all 4 BSCFDs. At SEM and histological analysis of 1 month, there were less inflammation(Kendall’s Tau-B=-0.818, p＝0.022), less vessel wall injury（Kendall’s Tau-B=-0.764, p＝0.032）and better endothelialization(Kendall’s Tau-B=0.818, p＝0.022) in BSCFDs. CONCLUSIONIn the rabbit model, the BSCFD is associated with less thrombus formation at acute stage, less inflammation, less vessel injury and better endothelialization on the device surface compared to the PFD.

Evolution of antiplatelet therapy in Japan for the management of cerebrovascular and cardiovascular disease: a survey using data from an insurance claims data information service

ABSTRACT Background Non-cardioembolic ischemic stroke (NCIS) and ischemic heart disease (IHD) require secondary prevention with antiplatelet therapy (APT). We investigated APT prescription status for patients with NCIS and IHD. Research design and methods This retrospective study utilized claims data from patients with NCIS and those who underwent percutaneous coronary intervention for IHD and received antiplatelet drugs. The study included Phases A (2015–2016), B (2017–2018), and C (2019–2020). We evaluated patient characteristics, APT prescription rates (dual [DAPT] and single [SAPT]), and prescriptions by NCIS subtype. Results In the NCIS cohort, the initial DAPT prescription rate increased over time (Phase A: 14.9%, B: 19.2%, C: 28.0%), but decreased to 6% after 3 months. Subsequently, 25% of patients did not receive APT. For IHD, DAPT duration decreased over time, with 12-month prescription rates of 48.0%, 43.1%, and 32.6% for Phases A, B, and C, respectively. SAPT prescriptions, predominantly aspirin, increased, and use of P2Y12 inhibitors also rose. Few patients (10%) did not receive APT. Conclusions Shorter DAPT duration/earlier switching to SAPT for NCIS and IHD have gained acceptance in regional medical care. A higher proportion of NCIS vs IHD patients did not receive APT in the chronic phase. Trial registration UMIN000052198.

Serological Evaluation of the Anti-coagulant Activity of the Classical Siddha Medicine -‘Veera Mezhugu’ in Wistar Albino Rats

In setting the basis for the management of arterial thrombosis, cardiac ischemic changes followed by any severe coronary atherosclerotic changes or any venous thrombosis, there is a conventional use of Acute thrombolytic agents, Anticoagulants with antiplatelet medications in general. These symptoms complex are mentioned as Thamaraga vaayu or Ruththira vaayu or Maaradaippu(Acute coronary syndrome) and Uthirakattu(thromboembolism) in siddha literatures. Veera mezhugu is one of the Siddha formulations chosen from Anuboga vaithiya navaneetham part-4, which is indicated for Uthirakattu and Thamaragavaayu. The drug prepared as per the Siddha literature. The drug has undergone safety studies and the efficacy studies in Wistar albino rats where the serum of the different groups with different doses are compared with the placebo control to evaluate the anti-coagulant potential. Coagulation profile of the three parameters of Activated partial thromboplastin time(APTT), Prothrombin time(PT) and International normalized ratio(INR) are taken for evaluation and had significant difference between the groups[p&lt;0.05].Serological analysis of the Wistar rats shows significant anticoagulant activity in a dose dependent manner.

NSAIDs, analgesics, antiplatelet drugs, and decline in renal function: a retrospective case-control study with SIDIAP database

IntroductionWe aim to explore the association between NSAIDs consumption, Symptomatic Slow Action Drugs for Osteoarthritis (SYSADOA), analgesics, and antiplatelet drugs, and decline in renal function by estimated Glomerular Filtration Rate (eGFR).MethodsWe performed a case-control study using the SIDIAP database in Catalonia. We considered defined cases, patients with an eGFR value ≤ 45 ml/min/1.73 m2 in the period 2010–2015 with a previous eGFR value ≥ 60, and no eGFR ≥ 60 after this period. Controls had an eGFR ≥ 60 with no previous eGFR < 60. Five controls were selected for each case, matched by sex, age, index date, Diabetes Mellitus and Hypertension. We estimated Odds Ratios (OR, 95% Confidence Intervals) of decline in renal function for drugs group adjusting with logistic regression models, by consumption measured in DDD. There were n = 18,905 cases and n = 94,456 controls. The mean age was 77 years, 59% were women. The multivariate adjusted model showed a low risk for eGFR decline for NSAIDs (0.92;0.88–0.97), SYSADOA (0.87;0.83–0.91) and acetaminophen (0.84;0.79–0.89), and an high risk for metamizole (1.07;1.03–1.12), and antiplatelet drugs (1.07;1.03–1.11). The low risk in NSAIDs was limited to propionic acid derivatives (0.92;0.88–0.96), whereas an high risk was observed for high doses in both acetic acid derivatives (1.09;1.03–1.15) and Coxibs (1.19;1.08–1.30). Medium and high use of major opioids shows a high risk (1.15;1.03–1.29). Triflusal showed high risk at medium (1.23;1.02–1.48) and high use (1.68;1.40–2.01).ConclusionWe observed a decline in renal function associated with metamizole and antiplatelet agent, especially triflusal, and with high use of acetic acid derivates, Coxibs, and major opioids. Further studies are necessary to confirm these results.

Cost-effectiveness of platelet function testing in dual antiplatelet therapy decision-making after intracranial aneurysm treatment with flow diversion.

Dual antiplatelet therapy (DAPT) use is the standard of practice after flow diversion (FD) for intracranial aneurysms (IAs). Yet, no consensus exists in the literature regarding the optimal regimen. Certain institutions utilize various platelet function testing (PFT) to assess patient responsiveness to DAPT. Clopidogrel is the most commonly prescribed drug during DAPT; however, up to 52% of patients can be non-responders, justifying PFT use. Additionally, prices vary significantly among antiplatelet drugs, often further complicated by insurance restrictions. We aimed to determine the most cost-effective strategy for deciding DAPT regimens for patients after IA treatment. A decision tree with Monte Carlo simulations was performed to simulate patients undergoing various three-month postoperative DAPT regimens. Patients were either universally administered aspirin alongside clopidogrel, ticagrelor, or prasugrel without PFT, or administered one of the former thienopyridine medications based on platelet reactivity unit (PRU) results after clopidogrel. Input data for the model were extracted from the current literature, and the willingness-to-pay threshold (WTP) was defined as $100,000 per QALY as per standard practice in the US. The baseline comparison was with universal clopidogrel DAPT without any PFT. Probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of the model. Utilizing PFT and switching clopidogrel to prasugrel if resistance is documented was the most cost-effective regimen compared to universal clopidogrel, with a base-case incremental cost-effectiveness ratio (ICER) of $-35,255 (cost $2,336.67, effectiveness 0.85). Performing PFT and switching clopidogrel to ticagrelor (ICER $-4,671; cost $2,995.06, effectiveness 0.84), universal prasugrel (ICER $5,553; cost $3,097.30, effectiveness 0.84), or universal ticagrelor (ICER $75,969; cost $3,801.36, effectiveness 0.84) were all more cost-effective than treating patients with universal clopidogrel (cost $3,041.77, effectiveness 0.83). These conclusions remain robust in probabilistic and deterministic sensitivity analyses. The most cost-effective strategy guiding DAPT after FD for IAs is to perform PFTs and switch clopidogrel to prasugrel if resistance is documented, alongside aspirin. The cost of PFT is strongly justified and recommended when deciding patient-specific DAPT regimens.

Importance of risk assessment, endoscopic hemostasis, and recent advancements in the management of acute non-variceal upper gastrointestinal bleeding

Acute non-variceal upper gastrointestinal bleeding (ANVUGIB) is a common medical emergency in clinical practice. While the incidence has significantly reduced, the mortality rates have not undergone a similar reduction in the last few decades, thus presenting a significant challenge. This editorial outlines the key causes and risk factors of ANVUGIB and explores the current standards and recent updates in risk assessment scoring systems for predicting mortality and endoscopic treatments for achieving hemostasis. Since ANUVGIB predominantly affects the elderly population, the impact of comorbidities may be responsible for the poor outcomes. A thorough drug history is important due to the increasing use of antiplatelet agents and anticoagulants in the elderly. Early risk stratification plays a crucial role in deciding the line of management and predicting mortality. Emerging scoring systems such as the ABC (age, blood tests, co-morbidities) score show promise in predicting mortality and guiding clinical decisions. While conventional endoscopic therapies remain cornerstone approaches, novel techniques like hemostatic powders and over-the-scope clips offer promising alternatives, particularly in cases refractory to traditional modalities. By integrating validated scoring systems and leveraging novel therapeutic modalities, clinicians can enhance patient care and mitigate the substantial morbidity and mortality associated with ANVUGIB.

ANew Fibrin-Heparine Coated Self-Expanding Stent for the Rescue Treatment of Intracranial Stenosis-aMulticentric Study.

Rescue intracranial stenting is necessary to provide sufficient recanalization after mechanical thrombectomy (MT) in patients with acute large vessel occlusions (LVO) due to an underlying intracranial atherosclerotic disease (ICAD). The CREDO heal is anovel stent that provides apotentially lower thrombogenicity due to surface modification. We present the first multicentric experience with the CREDO heal for acute rescue stenting. Data of 81patients who underwent rescue stenting after MT at 12centers in Germany and Spain were prospectively collected and retrospectively evaluated. Final mTICI2b‑3 was reached in 95.1% after median two MT maneuvers and stenting. Four periprocedural complications resulted in clinical deterioration (4.9%). Intraparenchymal hemorrhage occurred in one patient (1.2%) and functional independence at FU was reached by 42% of the patients. Most interventions were performed under Gp IIb/IIIa inhibitors. CREDO heal was effective and safe in our case series. However, more data is needed to define the optimal antithrombotic regime. The use under single antiplatelet medication is not supported by our study.

GGC repeat expansions in NOTCH2NLC cause uN2CpolyG cerebral amyloid angiopathy.

The expansion of GGC repeats within NOTCH2NLC leads to the translation of the uN2CpolyG protein, the primary pathogenic factor in neuronal intranuclear inclusion disease (NIID). This study aims to explore the deposition of uN2CpolyG as an amyloid in the vessel wall, leading to uN2CpolyG cerebral amyloid angiopathy (CAA)-related cerebral microbleeds (CMBs). A total of 97 patients with genetically confirmed NIID were enrolled in this study. We analyzed the presence of CMBs using susceptibility-weighted imaging sequences and compared general clinical information, cerebrovascular risk factors, stroke history, antiplatelet medication use, and MRI features between NIID patients with and without CMBs. We further performed hematoxylin and eosin (H&E), Perl's, Congo red, and Thioflavin S staining, ubiquitin, p62 and uN2CpolyG immunostaining on brain tissue obtained from four NIID patients. A total of 354 CMBs were detected among 41 patients with NIID, with nearly half located in the deep brain, one-third in the lobes, and approximately 20% in the infratentorial area. No significant differences in cerebrovascular disease risk factors or history of antiplatelet drug use were observed between patients with and without CMBs. However, patients with CMBs suffered a higher incidence of previous ischemic and hemorrhagic stroke events. This group also had a higher incidence of recent subcortical infarcts and a higher proportion of white matter lesions in the external capsule and temporal pole. Conversely, patients without CMBs showed higher detection of high signals at the corticomedullary junction on diffusion-weighted imaging and more pronounced brain atrophy. H&E staining showed blood vessel leakage and hemosiderin-laden macrophage clusters, and Prussian blue staining revealed brain tissue iron deposition. CMBs occurred more frequently in small vessels lacking intranuclear inclusions, and extensive degeneration of endothelial cells and smooth muscle fibres was observed mainly in vessels lacking inclusions. Congo red-positive amyloid deposition was observed in the cerebral vessels of NIID patients, with disordered filamentous fibres appearing under an electron microscope. Additionally, the co-localization of Thioflavin S-labeled amyloid and uN2CpolyG protein in the cerebral vascular walls of NIID patients further suggested that uN2CpolyG is the main pathogenic protein in this form of amyloid angiopathy. In conclusion, we reviewed patients with GGC repeat expansion of NOTCH2NLC from a novel perspective, providing initial clinical, neuroimaging, and pathological evidence suggesting that uN2CpolyG may contribute to a distinct type of CAA.

Safety of Antiplatelet Therapy in Noncardioembolic Ischemic Stroke With Thrombocytopenia: The CASE II Study.

There is scant evidence regarding the safety of antiplatelet therapy in acute ischemic stroke (AIS) patients with thrombocytopenia. Our study aims to address this concern by examining AIS patients with thrombocytopenia from a large database in real-world settings. We included patients with AIS with a platelet count <100×109/L who had complete records of antiplatelet drug use. Those requiring anticoagulation or having contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was 1-year all-cause mortality. A good clinical outcome was defined as functional independence, indicated by a modified Rankin Scale score of 0 to 2 at discharge. Propensity score matched analyses were used. We screened 169 423 patients with AIS from 90 stroke centers in the CASE II register, ultimately enrolling 2808 noncardioembolic patients with thrombocytopenia. In the propensity score matched analyses, no significant difference was observed between the antiplatelet and nonantiplatelet groups in terms of intracranial hemorrhage (odds ratio=0.855 [95% CI, 0.284-5.478]; P=0.160) or gastrointestinal bleeding (odds ratio=2.034 [95% CI, 0.755-5.478]; P=0.160). Antiplatelet therapy was associated with improved functional outcomes at discharge (odds ratio=1.405 [95% CI, 1.028-1.920]; P=0.033), and showed a trend towards reducing 1-year mortality (odds ratio=0.395 [95% CI, 0.152-1.031]; P=0.058). The use of antiplatelet therapy lessened as platelet count decreased in patients with AIS with thrombocytopenia. However, our findings suggest that antiplatelet medications remain safe and effective for this population.

Effect of different anticoagulants and antiplatelets on intraoral bleeding time during professional oral hygiene session

ObjectivePatients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context.Materials and methodsNinety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn’s post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc;ResultsControl patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001).ConclusionsBased on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT.Clinical significancebleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2–3 h before the next dose, without the need to temporarily suspend the medication.

Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study

BackgroundThe effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear.MethodsWe followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure).Results42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50–1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37–10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27–4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27–5.03; p = 0.008).ConclusionsIn outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

The humanized platelet glycoprotein VI Fab inhibitor EMA601 protects from arterial thrombosis and ischaemic stroke in mice.

Glycoprotein VI (GPVI) is a platelet collagen/fibrin(ogen) receptor and an emerging pharmacological target for the treatment of thrombotic and thrombo-inflammatory diseases, notably ischaemic stroke. A first anti-human GPVI (hGPVI) antibody Fab-fragment (ACT017/glenzocimab, KD: 4.1 nM) recently passed a clinical phase 1b/2a study in patients with acute ischaemic stroke and was found to be well tolerated, safe, and potentially beneficial. In this study, a novel humanized anti-GPVI antibody Fab-fragment (EMA601; KD: 0.195 nM) was developed that inhibits hGPVI function with very high potency in vitro and in vivo. Fab-fragments of the mouse anti-hGPVI IgG Emf6.1 were tested for functional GPVI inhibition in human platelets and in hGPVI expressing (hGP6tg/tg) mouse platelets. The in vivo effect of Emf6.1Fab was assessed in a tail bleeding assay, an arterial thrombosis model and the transient middle cerebral artery occlusion (tMCAO) model of ischaemic stroke. Using complementary-determining region grafting, a humanized version of Emf6.1Fab (EMA601) was generated. Emf6.1Fab/EMA601 interaction with hGPVI was mapped in array format and kinetics and quantified by bio-layer interferometry. Emf6.1Fab (KD: 0.427 nM) blocked GPVI function in human and hGP6tg/tg mouse platelets in multiple assays in vitro at concentrations ≥5 µg/mL. Emf6.1Fab (4 mg/kg)-treated hGP6tg/tg mice showed potent hGPVI inhibition ex vivo and were profoundly protected from arterial thrombosis as well as from cerebral infarct growth after tMCAO, whereas tail-bleeding times remained unaffected. Emf6.1Fab binds to a so far undescribed membrane proximal epitope in GPVI. The humanized variant EMA601 displayed further increased affinity for hGPVI (KD: 0.195 nM) and fully inhibited the receptor at 0.5 µg/mL, corresponding to a >50-fold potency compared with ACT017. EMA601 is a conceptually novel and promising anti-platelet agent to efficiently prevent or treat arterial thrombosis and thrombo-inflammatory pathologies in humans at risk.