Use Of Clopidogrel Research Articles

Comparative effectiveness of Cangrelor in patients with acute coronary syndrome undergoing percutaneous coronary intervention: an observational investigation from the M.O.Ca. registry

Cangrelor, the first intravenous P2Y12 inhibitor (P2Y12-I), has been approved on the basis of three large RCTs from the CHAMPION program which nevertheless have been criticized for the low bleeding risk of the enrolled patients, the large quote of chronic coronary syndromes, and the use of Clopidogrel as control arm even in the setting of acute coronary syndromes (ACS). We sought to investigate, in the setting of ACS, the comparative performance of Cangrelor in terms of in-hospital ischemic and haemorrhagic outcomes compared with the current gold-standard of oral P2Y12-I. The study retrospectively enrolled 686 consecutive patients admitted to the Divisions of Cardiology of Policlinico of Bari and L. Bonomo Hospital of Andria for ACS and treated with percutaneous coronary intervention. The study population was divided according to the P2Y12-I treatment strategy in two groups: patients given an oral P2Y12-I and patients receiving Cangrelor in the cath lab followed by an oral P2Y12-I. Clinical endpoints included death, ischemic and bleeding events occurring during hospital stay. Cangrelor treated patients presented higher clinical risk profile at presentation and faced higher death rate. However, after PS matching, in-hospital mortality resulted comparable between the groups and Cangrelor use was associated with reduced in-hospital definite stent thrombosis (p = 0.03). Data from our real-world registry highlight that, in the setting of ACS, Cangrelor is prevalently used in patients with very challenging clinical presentations. The adjusted analysis provides for the first time promising data on stent thrombosis reduction associated with Cangrelor use.

Contemporary Use of Ticagrelor vs Clopidogrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A GRACE Risk Score Stratification–Based Analysis in a Large-Scale, Real-World Study From China

ObjectiveTo evaluate potential gains in outcomes from ticagrelor-based strategy according to risk stratification by Global Registry of Acute Coronary Events (GRACE) score. MethodsA total of 19,704 patients discharged alive post–acute coronary syndrome who underwent percutaneous coronary intervention and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, composed of cardiac death, myocardial infarction, and/or stroke. Secondary outcomes included all-cause mortality and Bleeding Academic Research Consortium type 2 to 5 and 3 to 5 bleeding. ResultsThe ticagrelor group comprised 6432 (32.6%) patients and the clopidogrel group comprised 13,272 (67.4%) patients. During the follow-up period, there was a significant reduction in the incidence of ischemic events in patients treated using ticagrelor who had excessive risk of bleeding. According to the GRACE score, among low-risk patients, ticagrelor use compared with clopidogrel was not associated with decreased ischemic events (HR, 0.82; 95% CI, 0.57 to 1.17; P=.27) with excessive risk of Bleeding Academic Research Consortium type 3 to 5 bleeding (HR, 1.59; 95% CI, 1.16 to 2.17; P=.004). The risk of ischemic events (HR, 0.60; 95% CI, 0.41 to 0.89; P=.01) were lower in the intermediate- to high-risk patients treated with ticagrelor without significant difference in BARC type 3 to 5 bleeding risk (HR, 1.11; 95% CI, 0.75 to 1.65; P=.61). ConclusionThere was still a gap between guideline-indicated therapy and the clinical practice in a sizable subset of patients with acute coronary syndrome who underwent percutaneous coronary intervention. The GRACE risk score could identify patients who would derive benefit from the ticagrelor-based antiplatelet strategy.

Ticagrelor versus Clopidogrel, Drug of Choice for the Prevention of Stent Thrombosis after Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials

Objectives: The objective of this meta-analysis of randomized controlled trials was to compare the efficacy of ticagrelor versus Clopidogrel for preventing stent thrombosis (ST) following percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). Methodology: A comprehensive literature search was conducted using MEDLINE/PubMed, EMBASE, Web of Science, and the Cochrane Library. The inclusion criteria involved selecting randomized controlled trials that included patients with ACS undergoing PCI, comparing the use of ticagrelor and Clopidogrel, having a follow-up period of at least 30 days, and reporting data on ST. The meta-analysis was performed using the R statistical software version 4.1.1, and the "meta" package was utilized. The Mantel-Haenszel method was employed to calculate the relative risk (RR) and corresponding 95% confidence interval (CI) for comparing the risk of ST between the two treatment groups. Results: A total of seven randomized controlled trials were included in the analysis, comprising a population of 28,609 patients with ACS who were randomized to receive either ticagrelor or Clopidogrel in a ratio of 12,116:16,493. The cumulative rate of ST was found to be 2.2% (185/8,423) in the ticagrelor group and 2.7% (347/12,851) in the clopidogrel group. The meta-analysis revealed a significant decrease in the rate of ST with ticagrelor compared to Clopidogrel, demonstrating a relative risk of 0.71 (95% CI: 0.59 to 0.85). No heterogeneity was detected among the included studies, as indicated by an I2 value of 0% and a p-value of 0.463. Conclusion: In conclusion, the findings of this meta-analysis suggest that ticagrelor is a significantly more effective P2Y12 inhibitor than Clopidogrel for preventing ST following PCI in patients with ACS. These results support using ticagrelor as the preferred antiplatelet therapy in this patient population.

Association of ACE gene polymorphisms with in-stent restenosis by stent type (biomime, supraflex, xience).

Angiotensin Converting Enzyme or ACE is an exo-peptidase that causes the conversion of angiotensin I to angiotensin II, vasoconstriction, and aldosterone production. ACE gene polymorphism (I/D) affects enzyme activity and the risk of coronary artery disease or CAD. To examine the role of ACE (I/D) Gene Polymorphisms by Stent Types (Biomime, Supraflex, Xience) the Ace gene allele and genotype frequencies were determined in patients who underwent angioplasty. Patients with in-stent restenosis (ISR+) (N = 53) and patients as non-ISR group (ISR-) (N = 68) have been enrolled in this study based on follow-up angiography > 1 year after PCI. Frequencies of allele and genotypes of the ACE (I/D) variant were determined using polymerase chain reaction (PCR). The genotypes and allele frequencies were not significantly different between the studied populations (p-Values > 0.05). However, there was a significant difference between people with a history of Clopidogrel use in the ISR- and ISR + groups observed (p-Values > 0.005). In the present study, there was no statistically significant relationship between ACE (I/D) gene polymorphism and the incidence of restenosis in patients who underwent repeat angiography. The results showed that the number of patients who received Clopidogrel in the ISR + group was significantly less than the ISR- group. This issue can indicate the inhibitory effect of Clopidogrel in the recurrence of stenosis.

Predictors of Early Graft Thrombosis During Index Admission for Lower Extremity Arterial Bypass

Early graft thrombosis following lower extremity bypass (LEB) has long served as a quality indicator of surgical management. A granular understanding of the risk factors for graft thrombosis might help mitigate the potentially avoidable sequelae of this complication. Our study utilized Vascular Quality Initiative (VQI) data to identify predictor variables associated with graft thrombosis during index admission following LEB. We queried the VQI database for patients receiving unilateral infrainguinal LEB between 2003 and 2022. Patients undergoing concomitant PVI or suprainguinal bypass were excluded from our analysis. We formed six procedural groups: femoral-above knee popliteal bypass, femoral-below knee popliteal bypass, femoral-tibial bypass, femoral-ankle bypass, popliteal-tibial bypass, and popliteal-ankle bypass. Among these six groups, we utilized multivariable logistic regression modeling to identify technical and perioperative characteristics that predicted early graft thrombosis. Of the 54,504 LEB procedures that met inclusion criteria, 11,906 (21.8%) underwent femoral-above knee popliteal, 17,541 (32.2%) femoral-below knee popliteal, 19,224 (35.3%) femoral-tibial, 1414 (2.6%) femoral-ankle, 2661 (4.9%) popliteal-tibial, and 1758 (3.2%) popliteal-ankle bypass procedures. At the time of discharge, 1012 (1.9%) required intervention for a thrombotic intervention, and 814 (1.5%) were occluded. After adjusting for patient characteristics and comorbidities, we identified the following independent predictors for early graft thrombosis: female gender, distal target, symptomatic indication (rest pain and tissue loss), urgent/emergent presentation, and anticoagulation therapy, specifically warfarin and rivaroxaban. Conversely, the use of preoperative statin, aspirin and clopidogrel was protective against early graft thrombosis (Table). There were 9.5% of patients not receiving one or several of the protective medications identified (25.9% not receiving statins, 69.1% not receiving clopidogrel, and 27.6% not receiving aspirin). With regard to type of conduit used for LEB, native vein conduits demonstrated the lowest odds of graft thrombosis (Table, Figure). In this large national contemporary study of LEB, we have identified several factors including distal target, urgent/emergent presentation, preoperative warfarin or rivaroxaban therapy and use of nonautologous conduits as independent predictors of graft thrombosis. Conversely, preoperative statin, antiplatelet therapy and the use of native vein conduits were protective against graft thrombosis. Despite their beneficial effect, we identified that 9.5% of the LEB population are not receiving statin and/or antiplatelet therapies, which serves as a potential quality improvement initiative. Our findings suggest that utilization of native vein when possible, and promoting aggressive preoperative medical optimization including statin, aspirin and P2Y12 inhibitors may help avoid early graft occlusion in patients requiring lower extremity revascularization.TableMultivariable logistic regression model indicating technical and perioperative characteristics associated with early graft thrombosis after lower extremity arterial bypass surgeryPerioperative characteristicsOdds ratio (95% confidence interval)P valueAge0.99 (0.98-0.99)<.001Female sex1.32 (1.20-1.45)<.001White race1.10 (1.00-1.22).059Diabetes0.83 (0.75-0.92)<.001Dialysis1.02 (0.93-1.13).638Congestive heart failure1.03 (0.89-1.18).731Prior coronary artery bypass grafting0.87 (0.79-0.96).008Chronic obstructive pulmonary disease0.94 (0.83-1.05).266Smoking0.82 (0.73-0.93).002Aspirin0.73 (0.66-0.81)<.001Statin0.85 (0.77-0.95).003Baseline hemoglobin0.92 (0.90-0.95)<.001BMI1.00 (0.99-1.01).835Bypass type Femoral to above knee popliteal1 (reference)- Femoral to below knee popliteal1.62 (1.30-2.03)<.001 Femoral to tibial vessel3.18 (2.58-3.90)<.001 Femoral to ankle vessel4.41 (3.28-5.93)<.001 Popliteal to tibial vessel2.58 (1.98-3.37)<.001 Popliteal to ankle vessel3.15 (2.32-4.28)<.001Urgency Elective1 (reference)- Urgent1.74 (1.54-1.97)<.001 Emergent3.45 (2.75-4.34)<.001Conduit Native vein1 (reference)- Dacron1.09 (0.56-2.11).810 Polytetrafluoroethylene1.36 (1.20-1.55)<.001 Nonautologous biologic2.41 (1.95-2.97)<.001Indication Asymptomatic1 (reference)- Claudication1.02 (0.53-1.97).953 Rest Pain2.44 (1.28-4.66).007 Tissue loss2.18 (1.16-4.11).016 Acute ischemia3.39 (1.77-6.49)<.001 Not treated2.53 (1.34-4.77).004Per hour procedure time1.00 (1.00-1.00)<.001Preoperative P2Y12 antagonist therapy None1 (reference)- Clopidogrel0.81 (0.73-0.91)<.001 Prasugrel1.14 (0.58-2.24).697 Ticagrelor0.93 (0.49-1.75).818 Other0.81 (0.30-2.16).668 No, for medical reasons0.69 (0.50-0.96).027 Noncompliant1.35 (0.75-2.45).314Preoperative anticoagulation therapy None1 (reference)- Warfarin1.38 (1.16-1.65)<.001 Dabigatran1.06 (0.49-2.31).874 Rivaroxaban1.42 (1.15-1.75).001 Other1.54 (1.29-1.85)<.001 No, for medical reasons1.14 (0.74-1.74).548 Noncompliant2.35 (1.27-4.35).007Presented are odds ratios (95% confidence interval) from a multivariable model adjusting for age, sex, race, diabetes, dialysis, congestive heart failure, prior coronary artery bypass grafting, chronic obstructive pulmonary disease, smoking, use of aspirin, statin, anticoagulation, body mass index, urgency, indication, and total procedural time. Boldface entries indicate statistical significance. Open table in a new tab

Risk of secondary stroke subsequent to restarting aspirin in chronic stroke patients suffering from traumatic brain injury in Taiwan

Traumatic brain injury (TBI) is a silent epidemic that has been easily ignored. The safety and efficacy of restarting antiplatelet therapy after encountering traumatic brain injury (TBI) events remain a challenge. We explored the outcomes of restarting aspirin use on secondary stroke and mortality in patients with chronic stroke 4 weeks after suffering from a TBI episode in Taiwan. This study analyzed data from the National Health Insurance Research Database from January 2000 to December 2015. Overall, 136,211 individuals diagnosed with chronic stroke who suffered from acute TBI and received inpatient service were enrolled. The study outcomes were a competing risk of secondary stroke (ischemic and hemorrhagic) hospitalization and all-cause mortality. We identified a case group of 15,035 patients with chronic stroke (mean [SD] age of 53.25 [19.74] years; 55.63% male) who restarted aspirin use 4 weeks after suffering from TBI and a control group of 60,140 patients with chronic stroke (mean [SD] age of 53.12 [19.22] years; 55.63% male) who discontinued aspirin use after suffering from TBI. The risk of hospitalization of secondary ischemic stroke [adjusted hazard ratio (aHR) 0.694; 95% confidence interval (CI) 0.621–0.756; P < 0.001] and hemorrhagic stroke (aHR 0.642; 95% CI 0.549–0.723; P < 0.001) and all-cause mortality (aHR 0.840; 95% CI 0.720–0.946; P < 0.001) significantly decreased in patients with chronic stroke restarting aspirin use 1 month after suffering from TBI events (including intracranial hemorrhage) in comparison with the control subjects, regardless of those with or without diabetes mellitus, chronic kidney disease, myocardial infarction, atrial fibrillation, clopidogrel use, and dipyridamole use. Restarting aspirin use could lower the risks of secondary stroke (ischemic and hemorrhagic) hospitalization and all-cause mortality in patients with chronic stroke 1 month after suffering from TBI episodes.

Life-threatening Neutropenia After a Short Course of Dual Antiplatelet Therapy for Minor Stroke (P7-5.017)

<h3>Objective:</h3> We present a case of unexpected severe neutropenia in a patient prescribed a 21-day course of double antiplatelet therapy (aspirin and clopidogrel) for ischemic stroke. <h3>Background:</h3> Antiplatelet agents are the cornerstone of atherosclerotic stroke prevention. In recent years, trials such as CHANCE and POINT have popularized the use of a short (3–4 week) course of dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) after minor stroke or high-risk transient ischemic attack. While some P2Y12 inhibitors such as ticlopidine have been associated with neutropenia, this side effect is exceedingly rare with clopidogrel and has primarily been reported with prolonged use after coronary stenting. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> An 88-year-old woman presented with acute onset of left face, arm, and leg numbness. National Institutes of Health Stroke Scale was 1 for mild sensory loss. Non-contrast computed tomography (CT) of head showed no evidence of hemorrhage or acute ischemia. Brain magnetic resonance imaging revealed a small area of diffusion positivity in the right thalamus consistent with acute ischemic stroke. She was already taking aspirin 81mg daily; clopidogrel 75mg daily was added for a 21-day course. WBC count during admission had ranged from 4.11–6.27 K/uL. On post-stroke day 23, she presented with three days of malaise, abdominal pain, and fever to 102 °F. WBC and absolute neutrophil count were now markedly low (0.67, &lt;0.01 K/uL, respectively). CT scan of abdomen revealed enterocolitis and early appendicitis. She was diagnosed with febrile neutropenia and treated with broad-spectrum antibiotics and filgrastim. As there was no evidence of hematologic malignancy, it was concluded that her neutropenia was drug-induced secondary to clopidogrel. She gradually recovered and cell counts had normalized at follow-up. <h3>Conclusions:</h3> While rare, severe neutropenia can occur with even brief use of clopidogrel. With the widespread adoption of short course dual antiplatelet therapy after stroke, neurologists should be aware of this association. <b>Disclosure:</b> Dr. Culbertson has nothing to disclose. Dr. Blaszkowsky has nothing to disclose.

OA43 Peri-procedural management and incidence of bleeding events following musculoskeletal injections and aspirations in people on anticoagulation and antiplatelet therapy

Abstract Background/Aims Corticosteroid injections and aspirations are common interventions for managing musculoskeletal conditions and inflammatory arthritis. However, there remains limited safety evidence to support safe practice for injection decisions in people on anticoagulant therapy, particularly direct oral anticoagulant (DOAC) medications regarding incidence of bleeding events or complications. Although there is increasing evidence for warfarin continuation, there is considerable variation in published guidance, manufacturer recommendations and specialty approaches to peri-procedural management of DOACs. This study reports on peri-procedural practice regarding continuation or discontinuation, bleeding events and complication rates in people on anticoagulant and antiplatelet medication undergoing musculoskeletal injections. Methods A prospective observational study was undertaken (October 2018- December 2020) using weekly electronic database searches to identify musculoskeletal injection and aspiration procedures undertaken in orthopaedics, rheumatology and radiology in two large NHS providers. Reply-paid questionnaires were sent to all consecutive adults within two weeks of procedures. Information was collected on bleeding events/complications, anticoagulant/antiplatelet use, products, doses, indications, INR levels and checking, discontinuation/re-initiation, comorbidities, and other medications. Concurrent electronic searches were also undertaken for emergency attendance or admissions within 30 days following procedures to identify unreported serious bleeding events or complications. Results Electronic searching identified 5,080 musculoskeletal procedures with 1,338 (26.3%) respondents (ages 20-99 years) returning questionnaires. 356 received &amp;gt;1 procedure over the timeframe and 49 bilateral procedures. There were 45 reports of bleeding events and all non-clinically significant localised bruising of the skin: 25/1106 (0.2%) without anticoagulation or antiplatelet therapy; 20/232 (8.6%) with anticoagulant/antiplatelet therapy, occurring only with continued medications. Incidences included: warfarin with unknown INR levels (n= 2/36, 5.5%); DOACs (n=9/72, 12.5%) [apixaban (5/24, 21%), rivaroxaban (4/45, 8.8%)]; antiplatelets [clopidogrel (4/28, 14.2%), clopidogrel &amp; NSAID (1/4, 25%), aspirin (1/72, 1.3%), aspirin &amp; NSAID (2/11, 18.1%), NSAID (1/3, 33.3%)]. Localised bruising was more common with DOAC continuation, aspirin with NSAID use, clopidogrel use and older age. Only 3/72 respondents on DOACs reported instructions to interrupt medications (orthopaedics). There were no serious bleeding or thromboembolic events identified through electronic searches for any recipient within 30 days following procedures. Conclusion This observational study found no significant bleeding events resulting from musculoskeletal injections or aspirations with continuation of warfarin (INR &amp;lt; 3.80), direct oral anticoagulant use, antiplatelet or combination therapy. The only consequence reported was some occurrence of localised bruising, also reported without medication use. It was not universal practice to determine INR levels prior to procedures with warfarin use and common practice to continue DOACs and antiplatelet medications. This research adds to evidence that musculoskeletal injections and aspirations appear to be very low risk procedures for bleeding complications with continuation of anticoagulant and antiplatelet therapy. Further research on intra-articular or intra-tissue iatrogenic consequences with anticoagulant/antiplatelet use is needed to add to procedural risk/benefit evaluations. Disclosure C. McCrum: Grants/research support; Funding grant to provide professional education workshops-Novartis, Janssen. S. Grainger: None.

Electrochemical peptide nucleic acid functionalized α-Fe2O3/Fe3O4 nanosheets for detection of CYP2C19*2 gene.

The CYP2C19*2 gene carriers and non-carriers are closely related to the dosage of clopidogrel. To correctly guide the use of clopidogrel and promote individualized therapy, an ultra-sensitive electrochemical biosensor was developed for the detection of CYP2C19*2 gene. The heterogeneous α-Fe2O3/Fe3O4 nanosheets were prepared via the hydrothermal-calcination process, and the preparation parameters were optimized. The average diameter and thickness of the nanosheets were approximately 150nm and 53nm, respectively; and the saturation magnetization was 80.2emu/g. The α-Fe2O3/Fe3O4@Au nanosheets were prepared by sodium borohydride reduction method, and self-assembled to the electrode surface with magnetic field. Ultra-sensitive detection of CYP2C19*2 gene was realized through the recognition ability of strong single base mismatching of peptide nucleic acid and signal amplification effect of magnetic α-Fe2O3/Fe3O4@Au nanosheets. Under optimal detection conditions, the current had a good linear correlation with the negative logarithm of CYP2C19*2 gene concentration in the range 1pM-1nM, and the detection limit was 0.64pM (S/N = 3). Meanwhile, the electrochemical signals of target DNA and incomplete complementary DNA were detected. The constructed biosensor exhibited good selectivity, reproducibility, and stability, providing a promising strategy for the detection of other gene mutations by electrochemical biosensors.

Impact of continued clopidogrel use on outcomes of patients undergoing carotid endarterectomy

ObjectiveThe aim of this study was to evaluate the use of clopidogrel at the time of carotid endarterectomy (CEA) and its association with postoperative complications. MethodsSingle-institution, retrospective review of a prospective database. ResultsFrom 2010 to 2017, CEA was performed in 1066 consecutive patients (median age, 73 years; 66% men). The indications for operation included ≥70% asymptomatic stenosis (458; 43%), prior stroke (314; 29%), and transient cerebral or retinal ischemia (294; 28%). At the time of operation, 509 (48%) patients were taking aspirin alone, 441 (41%) were taking clopidogrel (374 in combination with aspirin, 67 as sole therapy), 83 (8%) were on no documented antiplatelet medication, and 33 (3%) were taking warfarin (with therapeutic international normalized ratio). The likelihood of clopidogrel use at the time of operation was higher for patients with a history of symptomatic carotid disease (P = .002). Over the study period, clopidogrel use increased from 31.9% in 2010 to 56.8% in 2017, which corresponds to an 11% (95% confidence interval, 6%-15%) increase annually. Postoperative strokes occurred in 15 patients (overall incidence, 1.4%), the majority of which were minor (12/15; 80%). Six strokes occurred in patients taking aspirin alone (6/509; 1.2%), two in patients on clopidogrel and aspirin (2/441; 0.5%), two in patients taking clopidogrel alone (2/67; 2.9%), three in patients on no documented antiplatelet medication (3/83; 3.6%), and two in those taking warfarin (one of which was secondary to a fatal intracranial hemorrhage within 30 days of discharge [2/33; 6.1%]). The 30-day mortality rate was 0.03% (3/1066); the risk for the combined endpoint of any stroke, death, or myocardial infarction (MI) was 2.3% (25/1066), and the risk for major stroke, death, or MI was 1.2%. There was no apparent association between clopidogrel use and the incidence of postoperative bleeding (P = .59) or any other postoperative complication (stroke, death, MI, cranial nerve injury; P = .15). ConclusionsClopidogrel use in our CEA practice has increased over time and has not been associated with an increased risk of postoperative complications, including bleeding. These data suggest that clopidogrel should not be discontinued prior to CEA and should be considered as part of ‘optimal medical therapy’ in patients undergoing CEA.

Efficacy and Safety of Ticagrelor versus Aspirin and Clopidogrel for Stroke Prevention in Patients with Vascular Disease: A Systematic Review and Meta-Analysis

Introduction: Currently, it is still controversial to treat stroke with ticagrelor alone. The purpose of our study was to systematically review and analyze the efficacy and safety of ticagrelor on cerebrovascular outcomes in patients with vascular risk factors. Methods: The PubMed, Cochrane Library, and Embase databases were systematically searched using the keywords stroke, ticagrelor, clopidogrel, and aspirin to identify randomized controlled trials (RCTs). Primary outcomes included reported stroke, ischemic stroke, and complex events; the secondary outcome was hemorrhagic stroke. The safety outcomes included major bleeding events, major or minor bleeding, and intracranial bleeding. The pooled odds ratio (OR), hazard ratios (HRs), and 95% confidence interval (CI) were calculated. We used I² statistics to assess statistical heterogeneity. Results: This meta-analysis included 15 RCTs involving 63,865 patients. Compared to the control group, ticagrelor reduced the risk of stroke (OR: 0.90; 95% CI: 0.81–0.99, p = 0.03; I² = 3%), ischemic stroke (OR: 0.81; 95% CI: 0.74–0.90, p < 0.0001; I² = 0%). Ticagrelor was not associated with an increased risk of all-cause mortality (OR: 0.94; 95% CI: 0.84–1.06, p = 0.31; I² = 62%), major bleeding (OR: 1.06; 95% CI: 0.97–1.15, p = 0.20; I² = 17%), hemorrhagic strokes (OR: 1.22, 95% CI: 0.76–1.96, p = 0.41; I² = 0%), and intracranial hemorrhage (OR: 1.06; 95% CI: 0.78–1.43, p = 0.71; I² = 12%). There was an increased risk of major or minor bleeding with ticagrelor compared to the control group (OR: 1.40; 95% CI: 1.19–1.66, p < 0.0001; I² = 56%). Additional analyses demonstrated that ticagrelor reduced the risk of incident recurrent stroke (HR: 0.83; 95% CI: 0.75–0.93, p = 0.0009; I² = 0%), recurrent ischemic stroke (HR: 0.79; 95% CI: 0.71–0.89, p < 0.0001; I² = 0%) among patients with a history of acute ischemic stroke (AIS) or transient ischemic attack (TIA). There were no significant differences in safety outcomes. Conclusion: Ticagrelor is slightly better than clopidogrel and aspirin in preventing stroke, especially ischemic stroke, with significant safety risks. For patients with a history of AIS/TIA, the use of ticagrelor was superior to the use of clopidogrel or aspirin in reducing the risk of subsequent stroke. We believe that ticagrelor is a potential alternative to aspirin or clopidogrel in some cases, especially for patients with CYP2C19 deficiency.

The Effect of Pre-operative use of Antiplatelets and Anticoagulants on Time to Surgery in Hip Fracture Patients.

Hip fractures are a major health concern resulting in significant morbidity worldwide. They are the leading cause of fall-related injuries amongst the elderly with high risk of death, and numbers are expected to rise with the growing elderly population. Expedited surgical repair has been proven to improve patient outcomes, however there are often multiple barriers to early surgery especially in the elderly. The use of antiplatelets and anticoagulation is a significant contributory factor to surgical delay. We conducted a retrospective, single centre study on hip fracture patients admitted to an acute care orthogeriatric unit over a 12-month period, aimed at determining the impact of pre-operative use of antiplatelets and anticoagulants on time to surgery (TTS) and its impact on one-year mortality rates. Amongst 404 eligible patients, 102 were on antiplatelets, 23 on anticoagulants and 279 were neither on antiplatelets or anticoagulants. Our study showed that patients taking clopidogrel (p<0.001) and DOACs (p=0.001) were more likely to have delayed surgery compared to those who were not on these agents. In addition, all patients on warfarin experienced surgical delay. Warfarin group also had highest mortality rates compared to other group and 10 times more likely to die within a year (p=0.001). The results from this study are consistent with existing literature, suggesting that the use of clopidogrel and anticoagulants have a negative impact on TTS in hip fracture patients. Strategies should be developed for patients on these medications to enhance their TTS.

Long-term use of clopidogrel versus ticagrelor or prasugrel in patients with acute myocardial infarction after percutaneous coronary intervention.

To compare the long-term clinical outcomes of dual antiplatelet therapy (DAPT) with clopidogrel and DAPT with ticagrelor or prasugrel in patients with acute myocardial infarction (AMI) who underwent coronary intervention. Between November 2011 and December 2015, a total of 13,104 patients with AMI were enrolled in the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry. Among them, 4,696 patients who received DAPT for more than 24 months were categorized into two groups: the clopidogrel group (n = 4,053) and ticagrelor or prasugrel group (n = 643). Propensity score matching (PSM) was used to reduce the bias due to confounding variables. Following PSM, the impacts of P2Y12 inhibitors on the clinical outcomes in both groups were compared during a 36-month clinical follow-up period. There were no significant differences in clinical outcomes in terms of cardiac death (7.1% vs. 9.7%, p = 0.101), stroke (1.4% vs. 1.0%, p = 0.436), major bleeding (0.5% vs. 0.8%, p = 0.478), major adverse cardiac events (MACE) (21.6% vs. 20.5%, p = 0.626), and net adverse cardiac event (NACE) (22.1% vs. 21.3%, p = 0.731) between the groups. The ticagrelor or prasugrel group had a lower incidence of recurrent percutaneous coronary intervention (PCI) (12.2% vs. 7.6%, p = 0.006) than the clopidogrel group. However, no differences were observed in the cumulative incidences of 3-year NACE between the ticagrelor or prasugrel and clopidogrel groups. Cumulative incidences of long-term NACE did not differ between the two groups. Therefore, the type and duration of DAPT should be customized for each patient with AMI.

Does pre-injury clopidogrel use increase the risk of intracranial haemorrhage post head injury in adult patients? A systematic review and meta-analysis

BackgroundSeveral current guidelines do not include antiplatelet use as an explicit indication for CT scan of the head following head injury. The impact of individual antiplatelet agent use on rates...

Retrospective analysis of immunosuppressive and anti-thrombotic protocols in nonassociative immune mediated hemolytic anemia in dogs.

Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune-mediated hemolytic anemia (na-IMHA) is weak. Investigate the efficacy of various drugs in na-IMHA. Two hundred forty-two dogs. Multi-institutional retrospective study (2015-2020). Immunosuppressive effectiveness was determined by time to packed cell volume (PCV) stabilization and duration of hospitalization through analysis by mixed model linear regression. Occurrence of disease relapse, death, and antithrombotic effectiveness, were analyzed using mixed model logistic regression. Use of corticosteroids vs a multi-agent protocol had no effect on time to PCV stabilization (P=.55), duration of hospitalization (P=.13), or case fatality (P=.06). A higher rate of relapse (P=.04; odds ratio: 3.97; 95% confidence interval [CI]: 1.06-14.8) was detected in dogs receiving corticosteroids (11.3%) during follow-up (median: 28.5 days, range: 0-1631 days) compared to multiple agents (3.1%) during follow up (median: 47.0 days, range: 0-1992 days). When comparing drug protocols, there was no effect on time to PCV stabilization (P=.31), relapse (P=.44), or case fatality (P=.08). Duration of hospitalization was longer, by 1.8 days (95% CI: 0.39-3.28 days), for the corticosteroid with mycophenolate mofetil group (P=.01) compared to corticosteroids alone. Use of clopidogrel vs multiple agents had no effect on development of thromboses (P ≥ .36). Addition of a second immunosuppressive agent did not alter immediate outcome measures but might be associated with a reduction in relapse. Use of multiple antithrombotic agents did not reduce incidence of thrombosis.

The use of ticagrelor versus clopidogrel in Malaysian patients with coronary artery disease undergoing percutaneous coronary intervention (PCI): Does the age tertile affect the platelet reactivity?

Abstract Funding Acknowledgements Type of funding sources: None. Background Previous studies have shown that the prevalence of cardiovascular diseases is related to the patient's age and gender differences, but the effect of age on platelet function remains controversial. Platelet function should be tested and its efficacy correlates with the age of patients undergoing percutaneous coronary intervention (PCI) using vasodilator-associated stimulated phosphoprotein (VASP). VASP is a gold standard to assess P2Y12 receptor inhibition among patients using ticagrelor or clopidogrel. Purpose We sought to compare the effect of ticagrelor versus clopidogrel on the platelet function of patients undergoing PCI and the correlation of age in this effect. Method This study was a prospective, randomized, parallel design, an open-label investigation conducted on Malaysian patients undergoing PCI. It included 84 patients (40 patients taking ticagrelor, and 44 patients taking clopidogrel). The induced platelet reactivity was assessed by measuring total whole blood at one standardized time point after 4 hours of loading dose of ticagrelor 180 mg or clopidogrel with 600 mg and by age tertiles. Result The study population consisted of 23 (57.5%) patients in Tertile 1 &amp;lt;60 years of age, 11 (27.5%) patients in Tertile 2 between 60-70 years of age and 6 (15.0%) patients in Tertile 3 &amp;gt;70 years of age. The number of patients who used ticagrelor was 17 (38.64%) in Tertile 1, 21 (47.73%) in Tertile 2, and 6 (13.64%) in Tertile 3 of those who used clopidogrel. The results of platelet reactivity index was high in the patients who used clopidogrel compared to the ticagrelor group, which were 52.3% and 2.5 %, P &amp;lt;0.001. This effect in the clopidogrel group included all age groups without exception and at different rates (52.9%, 52.4%, and 50%, P= 0.992), respectively, but this effect was numerical and not statistically significant. In contrast to the ticagrelor group, no numerical or significant effect was observed in all age groups (4.3%, 0.0%, and 0.0%, P= 0.259), respectively (Figure 1). In addition, the results of the current cross-sectional age classification study showed no statistical differences between the clopidogrel and ticagrelor groups based on non high platelet reactivity (NHPR) (P = 0.284, P = 0.270, P = 0.796 respectively) (Figure2). Conclusion Our study showed that age could not be considered a risk factor in the Malaysian population, as it did not significantly affect platelet aggregation in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI).

Antithrombotic therapy in patients with diabetes mellitus

The study discussed various possibilities of antithrombotic therapy in patients with diabetes mellitus. Patients with diabetes mellitus, regardless of whether they have cardiovascular diseases, have a high risk of thrombosis. A feature of the response to antiplatelet therapy is the higher resistance to acetylsalicylic acid and clopidogrel of patients with diabetes mellitus than patients without diabetes mellitus, which can reach 71.4% and 57.1%, respectively. With a decrease in the functional ability of the kidneys in patients with diabetic nephropathy, acetylsalicylic acid is a safe antiplatelet drug; the use of clopidogrel in these patients leads to an increase in the risk of general and cardiovascular mortality. In the absence of contraindications, acetylsalicylic acid is recommended for patients with diabetes mellitus for the secondary prevention of cardiovascular diseases and may be recommended for primary prevention in patients with high and very high cardiovascular risk. Clopidogrel is recommended for patients with diabetes mellitus only for the secondary prevention of intolerance to acetylsalicylic acid. With the development of acute coronary syndrome, patients with diabetes mellitus received double antiplatelet therapy using acetylsalicylic acid and any P2Y12 receptor blocker. In patients who received percutaneous coronary intervention, prasugrel or ticagrelor is recommended as the second component. Double antiplatelet therapy extended for 12 months is indicated for patients with diabetes mellitus with a very high cardiovascular risk and good tolerability. In non-valvular atrial fibrillation, direct oral anticoagulants, in the absence of contraindications, are the drugs of choice in patients with diabetes and creatinine clearance 30 mL/min for dabigatran and 15 mL/min for rivaroxaban and apixaban. With the development of terminal renal insufficiency, only warfarin has proven effectiveness. Combined antiplatelet and anticoagulant therapy is indicated for diabetes mellitus with coexisting atherosclerotic diseases with a high risk of thrombotic and low risk of hemorrhagic complications.

A comparison of antiplatelet therapy during the peri- and post-operative periods following flow-diverting stent insertion for unruptured intracranial aneurysms: A systematic review.

Flow diverters (FDs) are neuroendovascular stents indicated for the management of unruptured intracranial aneurysms. Due to their composition, dual antiplatelet therapy (DAPT) is essential during the peri- and post-operative periods to prevent thromboembolic events. However, there is limited consensus within the scientific community regarding which antiplatelets to use and dosing following neuroendovascular treatment of aneurysms. A systematic search of four electronic databases was conducted during November 2020 that included studies published between January 2010 and November 2020. Eligibility for inclusion included primary research articles, published in the English language and use of flow-diverting intracranial stents. Studies were excluded if they utilised combined therapies (e.g. FD with stent-assisted coiling), animal studies, clinical trial protocols and study population of less than 10 subjects. Eighteen studies were identified for inclusion with a total of 1312 patients with 1355 unruptured intracranial aneurysms treated with FDs. Of these, 13 studies primarily investigated the use of clopidogrel with aspirin with low rates of haemorrhagic and thromboembolic complications. A forest plot of nine of these studies showed average efficacy of 88% at 95% confidence interval (CI) (SD + 5%) with 63% heterogeneity. The large proportion of studies investigating clopidogrel and aspirin antiplatelet therapy presents a challenge in comparing antiplatelet regimens. Although prasugrel and ticagrelor have been identified as suitable alternatives to clopidogrel, these were based on studies with small cohort sizes. Glycoprotein IIb/IIIa inhibitors may be efficacious as rescue therapy for intra-procedural thrombosis. Further research is required to determine which antiplatelet is most suitable.

Risk factors and management outcomes in epistaxis: a tertiary centre experience.

Risk factors and outcomes associated with severe epistaxis are not well understood. This study explores the associations between epistaxis severity, comorbidities, use of antiplatelets or anticoagulants and management outcomes. This is a retrospective cross-sectional study of all epistaxis cases presenting to the emergency department at a tertiary academic hospital from January 2016 to December 2019. Epistaxis severity was defined as mild (no intervention), moderate (required cautery and/or packing) and severe (clinical instability with reversal products, surgical or radiological intervention). Univariable and multivariable regression analyses were undertaken, with risk factors and management outcomes analysed according to severity. A total of 543 patients with epistaxis (54.2% male, mean age 74.4 ± 15.7 years) were included in this study, with 14.7% (80) having severe epistaxis. Of these presentations 216 (39.8%) were on antiplatelets, while 207 (38.1%) were on anticoagulants. In univariate analyses, clopidogrel use, hereditary haemorrhagic telangiectasia (HHT), haematological malignancy, bleeding disorders and chronic liver disease (CLD) were associated with moderate to severe epistaxis (P < 0.05), while the use of rivaroxaban was inversely associated severity (P=0.002). Only HHT, haematological malignancy and CLD remained significant in multivariate models. Cautery as first-line management was infrequently utilized while anticoagulation was frequently withheld. A longer length of stay (1.1 days vs. 4.3 days; P < 0.001) and higher 2-week readmission rates (2.2% vs. 12.5%; P < 0.001) were noted with severe epistaxis compared with mild presentations. Epistaxis severity is associated with certain clinical conditions and poor outcomes. Despite recommended guidelines, variations in first-line management were evident.

Comparative Effectiveness of Ticagrelor, Prasugrel, and Clopidogrel for Secondary Prophylaxis in Acute Coronary Syndrome: A Propensity Score-Matched Cohort Study.

Comparative effectiveness evaluation of newer P2Y12 inhibitors (prasugrel and ticagrelor) compared with clopidogrel after acute coronary syndrome (ACS) is limited in real-world US populations. The objective of this study was to evaluate cardiovascular events based on ticagrelor, prasugrel, and clopidogrel use in a real-world patient setting. This retrospective cohort study used the IBM MarketScan database (January 1, 2013, to December 31, 2018) to create three propensity score-matched pairs: ticagrelor vs. clopidogrel (N= 21,719), prasugrel vs. clopidogrel (N= 11,513), and prasugrel vs. ticagrelor (N= 11,065). The primary outcome was a composite of myocardial ischemia, unstable angina, stroke, and heart failure hospitalization. These groups were compared in a time-to-event analysis for the primary outcome at 30, 90, and 180 days following P2Y12 inhibitors initiation after percutaneous coronary intervention. Compared with clopidogrel, ticagrelor use suggested a 10% reduction in the primary outcome at 90 days (hazard ratio (HR): 0.90, 95% confidence interval (CI): 0.82-0.99). There were no differences for all other matched pairs or follow-up combinations. In the subgroup analysis of females, the results suggested a risk reduction of 27% for prasugrel at 30 days (HR: 0.73, 95% CI: 0.53-1.00) and 17% for ticagrelor at 90 days (HR: 0.83, 95% CI: 0.70-0.98) when compared with clopidogrel. Among patients treated with bare-metal stents, the results suggested that prasugrel vs. ticagrelor was associated with a 55% and 33% reduced risk for the primary outcome at 30 days and 180 days, respectively. With limited evidence in the United States comparing these drugs, this study helps inform clinicians when choosing P2Y12 inhibitors after ACS.