Use Of Antiplatelet Agents Research Articles

Lower-limb peripheral arterial disease and amputations in people with diabetes: Risk factors, prognostic value and management

Lower-limb peripheral arterial disease (PAD), is a common manifestation of systemic atherosclerosis, resulting from a partial or complete obstruction of at least one lower-limb arteries. PAD is a major endemic disease with an excess risk of major cardiovascular events and death. It also leads to disability, high rates of lower-limb adverse events and non-traumatic amputation. In patients with diabetes, PAD is particularly frequent and has a worse prognosis than in patients without diabetes. The risk factors of PAD are comparable to those for cardiovascular disease. The ankle-brachial index is usually recommended to screen PAD despite its limited performance in patients with diabetes, affected by the presence of peripheral neuropathy, medial arterial calcification, incompressible arteries and infection. Toe brachial index and toe pressure emerge as alternative screening tools. The management of PAD requires strict control of cardiovascular risk factors including diabetes, hypertension and dyslipidaemia, the use of antiplatelet agents and lifestyle management, to reduce cardiovascular adverse events, but few randomized controlled trials have evaluated the benefits of these treatments in PAD. Several advances have been achieved in endovascular and surgical revascularization procedures, with obvious improvement in PAD prognosis. Further studies are required to increase our understanding of the pathophysiology of PAD and to evaluate the interest of different therapeutic strategies in the occurrence and progression of PAD in patients with diabetes. Here, we present a narrative and contemporary review to synthesize the key epidemiology findings, screening and diagnosis methods, and major therapeutic advances regarding PAD in patients with diabetes.

Interventions for preventing and treating kidney disease in IgA vasculitis.

Interventions for preventing and treating kidney disease in IgA vasculitis.

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...

Physician Approaches to Antithrombotic Therapies for Recently Symptomatic Carotid Stenosis.

Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

Comparison of warfarin with direct oral anticoagulants for thromboembolic prophylaxis after catheter ablation of ventricular tachycardia.

Thromboembolic events after catheter ablation of ventricular tachycardia (VT) can result in significant morbidity. Thromboembolic prophylaxis after catheter ablation can be achieved by the use of antiplatelet agents, vitamin K antagonists, or direct oral anticoagulants (DOACs). The relative safety and efficacy of these modes of prophylaxis are uncertain. We sought to compare the outcomes of patients who received warfarin or DOACs for thromboembolic prophylaxis after catheter ablation of VT. Anticoagulation with DOACS was started after left ventricular VT ablation in a series of 42 consecutive patients with structural heart disease (67 ± 11 years, 3 women, ejection fraction 32 ± 14%). Duration of hospital stay, bleeding episodes, and thromboembolic events were compared to a historic consecutive group of patients (n = 38, 65 ± 13 years, 14 women, ejection fraction 36 ± 13%) in whom anticoagulation with a formerly described protocol of heparin and vitamin K antagonist was used after VT ablation procedures. Hospital stay was significantly shorter in the group where DOACs were used as compared to vitamin K antagonists (3.3 ± 1.8 vs. 5.0 ± 2.5 days postablation; p = 0.001) without an increase of bleeding or thromboembolic events. Anticoagulation with DOACs is safe and shortens hospital stay in patients with structural heart disease undergoing left ventricular VT ablation procedures.

Antithrombotics prescription pattern and clinical outcomes in atrial fibrillation patients with type 2 diabetes mellitus

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) and Diabetes mellitus (DM) often coexist. As DM is considered while calculating the thromboembolic risk for AF patients, little is known about the prescription pattern of antithrombotic therapies in patients with AF and DM and their clinical outcomes. Purpose In this subsidiary study, we examined the prescription patterns of antithrombotic therapies and clinical outcomes of AF patients with type 2 DM. Methods We analyzed data from a single-center cohort of patients with a primary diagnosis of AF in a tertiary cardiac referral hospital in Malaysia from 1st January 2018 to 31st December 2020. Patients' clinical data and information related to antithrombotic therapy were traced through electronic Hospital Information system. A data collection form was used for data collection. The primary endpoint of the study was a composite cardiovascular (CV) event which consists of all-cause mortality, acute coronary syndrome (ACS), ischemic stroke and transient ischemic attack (TIA). The safety endpoint of the study was a bleeding event, defined as hemoglobin drop more than 2 g/dl, blood transfusion and bleeding at critical area. Results Of the 1006 AF patients (59.2% male; mean age 64.2 (12.1) years), 400 (39.8%) had a history of DM. Of these, 45.8% (n=183) were using warfarin; 46.5% (n=159) used direct oral anticoagulant (DOAC), 54.0% (n=216) used a single antiplatelet, 11.5% (n=46) used a double antiplatelet, 8.0% (n=32) used triple therapy which consists of two antiplatelet agents with one anticoagulant. The use of single antiplatelet agent (54.0% vs 46.4%, p=0.018) and double antiplatelet agents (11.5% vs 7.1%, p=0.016) was significantly associated with AF with DM patients, whereas there was no association between anticoagulant use and AF patients with or without DM (85.5% vs 82.5%, p=0.209). There was no association in composite CV events between AF patients with or without DM (12.0% vs 10.4%, p=0.427). The proportion of subjects who reported having bleeding events were also did not differ by the presence of AF patients with or without DM. (4.5% vs 2.8%, p=0.151). Conclusion Diabetes was associated with increased use of antiplatelet agents; however, DM was not associated with increased risk of composite CV events and bleeding events in patients with concurrent AF. The lack of an association between diabetes and CV risk contrasts with previous research, which could be due to improved diabetes treatment in this cohort of patients with relatively low fasting sugar readings. Further study on the degree of blood glucose as measured by glycosylated hemoglobin (HbA1c) is needed to confirm the finding.

Antiplatelet Agents and Oral Anticoagulant Use in Patients with Atrial Fibrillation and Carotid Artery Disease After First-Time Ischaemic Stroke

IntroductionPeople with atrial fibrillation (AF) frequently have competing mechanisms for ischaemic stroke, including extracranial carotid atherosclerosis. The objective of this study was to determine associations between use of oral anticoagulants (OACs) plus antiplatelet agents (APA) after ischaemic stroke and outcomes for patients with AF and carotid artery disease.Patients and MethodsA retrospective cohort study was conducted. Participants receiving OACs with or without APA were propensity score–matched for age, sex, ethnicity, co-morbidities and presence of cardiac and vascular implants and grafts. Outcomes were 1-year mortality, recurrent stroke and major bleeding.ResultsOf 5708 patients, 24.1% (n=1628) received non-vitamin K antagonist OACs (NOACs) with no APA, 26.0% (n=1401) received NOACs plus APA, 20.7% (n=1243) received warfarin without APA and 29.2% (n=1436) received warfarin plus APA. There was no significant difference in risk of recurrent stroke between the groups. Compared to receiving NOACs without APA, receiving warfarin plus APA was associated with a higher risk of mortality (hazard ratio (HR) 1.51 (95% confidence interval (CI) 1.20, 1.89)) and major bleeding (HR 1.66 (95% CI 1.40, 1.96)). Receiving NOACs plus APA was also associated with a higher risk of major bleeding compared to NOACs without APA (HR 1.27 (95% CI 1.07, 1.51), respectively).ConclusionsThe results suggest for patients with AF and carotid artery disease after ischaemic stroke, receiving NOACs without APA is associated with a lower risk of major bleeding with no negative impact on recurrent stroke or mortality. Evidence from randomised trials is needed to confirm this finding.

Prediction and Implications of Edoxaban-Associated Bleeding in Patients after Critical Illness.

In this retrospective study, we aimed to identify the risk factors for bleeding in patients after critical illness during edoxaban treatment. Data from patients who received edoxaban after critical illness at the Emergency Department at a tertiary care hospital were obtained from the hospital medical records. Multivariate analysis revealed the risk factors for edoxaban-associated bleeding. Additionally, we developed an edoxaban-associated bleeding score (EAB score) based on these results. The derived EAB score was compared with the HAS-BLED score using receiver operating characteristic (ROC) curve analysis. Bleeding was observed in 42 of 114 patients (36.8%). We identified the following bleeding predictors (odds ratios, 95% confidence interval, score points) using multivariate analysis: concomitant use of antiplatelet agents (6.759, 2.047-22.32, 2 points), concomitant use of P-glycoprotein inhibitors (3.825, 1.484-9.856, 1 point), prothrombin time (PT)% following edoxaban administration of <75% and ≥60% (2.507, 0.788-7.970, 1 point), and PT% following edoxaban administration of <60% (11.23, 3.560-35.42, 3 points). The ROC curve analysis revealed an area under the curve of 0.826 for the EAB score and 0.625 for the HAS-BLED score. Under appropriate edoxaban dosing regimens in patients after critical illness, a combination of antiplatelet agents, P-gp inhibitors, and a low PT% following edoxaban administration were identified as strong risk factors for bleeding.

Antithrombotic therapy in COVID-19 patients

Recently, there have been published the data of large randomized trials on the use of antithrombotic agents for reducing a risk of thromboembolic complications, multiple organ failure and mortality in COVID-19 patients. However, principles of selecting optimal therapy remain open. Strategies for the use of antithrombotic drugs in outpatient and inpatient settings, thromboprophylaxis in specific patient populations, and treatment of acute thrombosis in hospitalized COVID-19 patients are being developed. In October 2021, the International Society on Thrombosis and Hemostasis (ISTH) formed an interdisciplinary international panel of experts to develop recommendations for use of anticoagulants and antiplatelet agents in COVID-19 patients. Expert opinions are published. Here, we summarize all the publications available globally at the present time on this issue, obtained by using the principles of evidence-based medicine.

Multiple Antiplatelet Therapy in Ischemic Stroke Already on Antiplatelet Agents Based on the Linked Big Data for Stroke.

Optimal antiplatelet strategy for patients with ischemic stroke who were already on single antiplatelet therapy (SAPT) remains to be elucidated. This study aimed to evaluate the effect of different antiplatelet regimens on vascular and safety outcomes at 1 year after non-cardioembolic stroke in patients previously on SAPT. We identified 9,284 patients with acute non-cardioembolic ischemic stroke that occurred on SAPT using linked data. Patients were categorized into three groups according to antiplatelet strategy at discharge: 1) SAPT; 2) dual antiplatelet therapy (DAPT); and 3) triple antiplatelet therapy (TAPT). One-year outcomes included recurrent ischemic stroke, composite outcomes (recurrent ischemic stroke, myocardial infarction, intracerebral hemorrhage, and death), and major bleeding. Of 9,284 patients, 5,565 (59.9%) maintained SAPT, 3,638 (39.2%) were treated with DAPT, and 81 (0.9%) were treated with TAPT. Multiple antiplatelet therapy did not reduce the risks of 1-year recurrent stroke (DAPT, hazard ratio [HR], 1.08, 95% confidence interval [CI], 0.92-1.27, P = 0.339; TAPT, HR, 0.71, 95% CI, 0.27-1.91, P = 0.500) and 1-year composite outcome (DAPT, HR, 1.09, 95% CI, 0.68-1.97, P = 0.592; TAPT, HR, 1.46, 95% CI, 0.68-1.97, P = 0.592). However, the TAPT groups showed an increased risk of major bleeding complications (DAPT, HR, 1.23, 95% CI, 0.89-1.71, P = 0.208; TAPT, HR, 4.65, 95% CI, 2.01-10.74, P < 0.001). Additional use of antiplatelet agents in patients with non-cardioembolic ischemic stroke who were already on SAPT did not reduce the 1-year incidence of vascular outcomes, although it increased the risk of bleeding complications.

High intratumoral susceptibility signal grade on susceptibility-weighted imaging: a risk factor for hemorrhage after stereotactic biopsy.

This study aimed to examine the association of preoperative intratumoral susceptibility signal (ITSS) grade with hemorrhage after stereotactic biopsy (STB). The authors retrospectively reviewed 66 patients who underwent STB in their institution. Preoperative factors including age, sex, platelet count, prothrombin time-international normalized ratio, activated thromboplastin time, antiplatelet agent use, history of diabetes mellitus and hypertension, target location, anesthesia type, and ITSS data were recorded. ITSS was defined as a dot-like or fine linear low signal within a tumor on susceptibility-weighted imaging (SWI) and was graded using a 3-point scale: grade 1, no ITSS within the lesion; grade 2, 1-10 ITSSs; and grade 3, ≥ 11 ITSSs. Postoperative final tumor pathology was also reviewed. The association between preoperative variables and the size of postoperative hemorrhage was examined. Thirty-four patients were men and 32 were women. The mean age was 66.6 years. The most common tumor location was the frontal lobe (27.3%, n = 18). The diagnostic yield of STB was 93.9%. The most common pathology was lymphoma (36.4%, n = 24). The ITSS was grade 1 in 37 patients (56.1%), grade 2 in 14 patients (21.2%), and grade 3 in 15 patients (22.7%). Interobserver agreement for ITSS was almost perfect (weighted kappa = 0.87; 95% CI 0.77-0.98). Age was significantly associated with ITSS (p = 0.0075). Postoperative hemorrhage occurred in 17 patients (25.8%). Maximum hemorrhage diameter (mean ± SD) was 1.78 ± 1.35 mm in grade 1 lesions, 2.98 ± 2.2 mm in grade 2 lesions, and 9.51 ± 2.11 mm in grade 3 lesions (p = 0.01). Hemorrhage > 10 mm in diameter occurred in 10 patients (15.2%), being symptomatic in 3 of them. Four of 6 patients with grade 3 ITSS glioblastomas (66.7%) had postoperative hemorrhages > 10 mm in diameter. After adjusting for age, ITSS grade was the only factor significantly associated with hemorrhage > 10 mm (p = 0.029). Compared with patients with grade 1 ITSS, the odds of postoperative hemorrhage > 10 mm in diameter were 2.57 times higher in patients with grade 2 ITSS (95% CI 0.31-21.1) and 9.73 times higher in patients with grade 3 ITSS (95% CI 1.57-60.5). ITSS grade on SWI is associated with size of postoperative hemorrhage after STB.

Chronic Subdural Hematoma

Chronic subdural haematoma (CSDH) is an encapsulated collection of old blood between the dura mater and arachnoid caused by tear of bridging veins. Chronic subdural haematoma is considered when the blood is more than three weeks old. It is fairly common disease, especially in the elderly with incidence ranging 1.72 to 7. 35 per 100,000 population with male predominance. Elderly population is associated co- morbidities that can impact on immediate postoperative outcome and overall survival. Although history of trivial trauma is present in majority of cases but some cases may be secondary to coagulation defect, intracranial hypotension, and use of anticoagulant and antiplatelet agents. It commonly presents with headaches, confusion, drowsiness, vomiting, and seizures. On examination, patient have various neurological deficits including a low Glasgow coma scale, hemiparesis/hemiplegia, ocular palsy, and other deficits are seen .Diagnosis is usually confirmed by NCCT scan head however MRI are indicated for better visualisation of multiloculated intrahaematoma membranes. Management of this condition is mostly surgery but some patients have also been managed conservatively with steroids. Steroids have been used in patient who have minor headache and also used in patients who are unfit for surgery.

Survival outcomes of patients with concomitant acute variceal bleeding and acute coronary syndrome, and the role of antiplatelet agents: an institutional experience from a lower middle-income Country

BackgroundThere is strong evidence demonstrating the incidence of Acute Coronary Syndrome (ACS) among patients with cirrhosis, with the initiation of antiplatelet therapy being subject to debate due to an increased risk of bleeding. This study aimed to determine mortality among patients presenting with concomitant Acute Variceal Bleeding (AVB) and ACS at Index admission. Furthermore, the recurrence of AVB and ACS among patients discharged with or without antiplatelet therapy was determined.MethodsThis retrospective study was conducted at the Aga Khan University Hospital, Karachi, Pakistan on patients ≥ 18 years of age admitted to our ER with concomitant ACS and AVB between January 2002 to December 2017. Follow-up for 6 months or till death (if < 6 months), was observed, to help determine the incidence of recurrent AVB and ACS. The incidence of AVB and ACS was then compared amongst patient groups based on the usage of anti-platelet drugs on discharge.ResultsA total of 29 patients were included, with a mean age of 58.7 ± 11.0 years. Seven patients died on admission, having worse underlying liver disease. No mortality was reported among the remaining 22 patients. All 22 patients underwent surveillance endoscopy with variceal band ligation until obliteration, as needed. Only 7 patients from the surviving cohort received antiplatelet therapy. After 6.05 ± 1.1 months of follow-up, 1/22 (4.5%) developed recurrent AVB and 2/22 (9.1%) developed cardiovascular events. Importantly, there was no significant difference in the incidence of recurrent AVB (P = 1.000) and ACS (P = 0.091), depending on the use of antiplatelet therapy.ConclusionConcomitant AVB and ACS is a severe disorder with increased mortality among cirrhotic patients at presentation. The incidence of AVB does not seem to exacerbate with the use of antiplatelet agents, provided successful obliteration of varices is achieved using elective band ligation.

Bleeding risk in patients with multiple myeloma treated for venous thromboembolism: a MarketScan analysis

BackgroundMultiple myeloma (MM) is associated with high risk of venous thromboembolism (VTE). Thromboprophylaxis is thoroughly studied in MM. Contrarily, studies assessing the risk of bleeding in people with MM on anticoagulation are lacking. ObjectivesTo determine the rate of serious bleeding in patients with MM receiving anticoagulation for VTE and the clinical factors associated with bleeding risk. MethodsUsing the MarketScan commercial database, we identified 1298 people with MM treated with anticoagulation for incident VTE events between 2011 and 2019. Hospitalized bleeding was identified using the Cunningham algorithm. Rates of bleeding were calculated and Cox regression identified risk factors for bleeding. ResultsBleeding occurred in 51 (3.9%) cases during median follow-up of 1.13 years. Rate of bleeding among patients with MM on anticoagulation was 24.0 per 1000 person-years. In adjusted regression, factors associated with increased bleeding included age (HR, 1.31 per 10-year increase; 95% CI, 1.03-1.65), Charlson comorbidity index (HR, 1.29 per SD increase; 95% CI, 1.02-1.58), use of antiplatelet agents (HR, 2.4; 95% CI, 1.03-5.68), diabetes (HR, 1.85; 95% CI, 1.06-3.26), and renal disease (HR, 1.80; 95% CI, 1.05-3.16). Cumulative incidence of bleeding was 4.7%, 3.2%, and 3.4% for warfarin, low molecular weight heparin, and direct oral anticoagulants, respectively. ConclusionIn this real-world analysis, the rate of bleeding in people with MM on anticoagulation was comparable to those in other subsets of cancer-related VTE. Bleeding rate was lower with low molecular weight heparin and direct oral anticoagulants than warfarin. Higher comorbidity index, diabetes, antiplatelet agent use, and renal disease were risk factors for serious bleeding.

Drug-induced non-traumatic intracranial hemorrhage associated with the use of anticoagulants and antiplatelet agents

Intracranial hemorrhage (ICH) is characterized by a high level of disability and mortality. One of the most important reasons that lead to an increased risk and an increase in the ICH prevalence are antithrombotic drugs: anticoagulant, antiplatelet and thrombolytic. The main risk factors for ICH are advanced age, arterial hypertension, and the use of antithrombotic drugs of different groups. Treatment of ICH while taking drugs affecting hemostasis, is an extremely difficult task and there is not enough sufficiently convincing recommendations and evidence. The decision to resume therapy with the drug, that led to the development of ICH, and the timing of this resumption, is also not a completely clear problem that requires a balance between ischemic and hemorrhagic complications. The most important aspect of prevention is strict adherence to current recommendations regarding combinations of antithrombotic drugs and protocols for thrombolytic therapy, which will minimize the risks of ICH.

Apixaban in Patients With Post-Myocardial Infarction Left Ventricular Thrombus: A Randomized Clinical Trial

BackgroundDirect oral anticoagulants are frequently used to treat post-myocardial infarction (MI) left ventricular thrombus (LVT). This study was conducted to evaluate the efficacy and safety of use of apixaban, compared to the standard warfarin therapy, in post-MI LVT. MethodsThis open-label, randomized controlled trial included patients with post-acute or recent anterior wall MI with transthoracic echocardiography-confirmed LVT. Patients were randomized to receive either apixaban 5 mg twice daily or warfarin to achieve an international normalized ratio of 2-3, in addition to dual antiplatelet therapy. The primary endpoint was LVT resolution at 3 months, with a noninferiority margin of 95% for apixaban compared to warfarin. The secondary endpoint was major adverse cardiovascular events (MACE) or any relevant bleeding according to the Bleeding Academic Research Consortium (BARC) classification. ResultsFifty patients were enrolled from 3 centres. The use of dual or single antiplatelet agents was similar in the 2 groups. The number of 1-, 3-, and 6-month LVT resolutions were 10 (40.0%), 19 (76.0%), and 23 (92.0%) in the apixaban group, and 14 (56%), 20 (80.0%), and 24 (96.0%) in the warfarin group, respectively, without significant differences (P < 0.036 for noninferiority at 3 months). Patients taking warfarin required longer hospital stays and more outpatient visits. Multivariate adjustment analysis revealed left ventricular aneurysm, larger baseline LVT area and lower left ventricular ejection fraction to be independent predictors of LVT persistence at 3 months. No MACE occurred in either group; 1 BARC-2 bleeding event occurred with warfarin. ConclusionsApixaban was not inferior to warfarin in the resolution of post-MI LVT.

Effect of antiplatelet agents on Escherichia coli sepsis mechanisms: A review.

Despite ever-increasing improvements in the prognosis of sepsis, this condition remains a frequent cause of hospitalization and mortality in Western countries. Sepsis exposes the patient to multiple complications, including thrombotic complications, due to the ability of circulating bacteria to activate platelets. One of the bacteria most frequently implicated in sepsis, Escherichia coli, a Gram-negative bacillus, has been described as being capable of inducing platelet activation during sepsis. However, to date, the mechanisms involved in this activation have not been clearly established, due to their multiple characteristics. Many signaling pathways are thought to be involved. At the same time, reports on the use of antiplatelet agents in sepsis to reduce platelet activation have been published, with variable results. To date, their use in sepsis remains controversial. The aim of this review is to summarize the currently available knowledge on the mechanisms of platelet activation secondary to Escherichia coli sepsis, as well as to provide an update on the effects of antiplatelet agents in these pathological circumstances.

Incidence and outcome of gastrointestinal bleeding in patients receiving aspirin with or without clopidogrel over 10 years- An observational study.

To determine the long-term incidence and outcome of gastrointestinal (GI) bleeding in users of aspirin with (dual antiplatelet therapy, DAPT) or without clopidogrel. Prospective hospital based 12-year study. There were 1047 patients on either aspirin 150 md/day alone (n = 574, 54.8%) or aspirin 75 md/day + clopidogrel 75 md/day (n = 473, 45.2%) were followed up for any incident GI bleed, rebleed and mortality. Those simultaneously using other drugs known to cause GI bleeding were excluded. Comorbidities, concomitant use of proton pump inhibitors and statins were noted. GI bleed occurred in 11.8% after 8,683 person years of follow up. 56 (45%) patients had lower GI source of bleed [colon 9 (7%), small gut 47 (38%)] and 68 (55%) had upper GI source [duodenum 39 (32.3%), stomach 28 (22.6%) and oesophagus 1 (0.1%)]. Whereas stomach and duodenum were the chief sites in the first year, small gut predominated in later years. The cumulative bleeding rate after 1, 5 and 10 years was 5%, 8% and 11%, respectively, higher in the DAPT group. Bleeding stopped spontaneously in 98% on drug withdrawal, and 7.3% patients rebled in the next 6.2 years. The overall mortality was 33.1% but only 1.6% was due to the bleed being significantly lower in the DAPT group. On multivariate analysis coronary interventions, diabetes mellitus, renal and multiorgan dysfunction were the significant predictors of GI bleed and mortality. Though the incidence and mortality are low, GI bleed increases with longer use of antiplatelet agents predominantly from the lower GI tract.

Time trends in antithrombotic therapy prescription patterns: Real-world monocentric study in hospitalized patients with atrial fibrillation.

Since 2010, the European Society of Cardiology has extended prescription criteria for oral antithrombotic therapy (OAT) in atrial fibrillation (AF). Direct oral anticoagulants (DOACs) were upgraded from an IIAa recommendation in 2012 to an IA in 2016. In real-world scenarios, however, OAC prescription is still suboptimal, mainly for DOACs. To evaluate OAT temporal prescription patterns in a cohort of patients hospitalized with AF in a Cardiology Department. A retrospective observational study was conducted on a cohort of hospitalized patients in a secondary setting (Trapani, Italy) from 2010 to 2021 with AF as the main or secondary diagnosis. For 4089 consecutive patients, the variables extracted from the Cardiology department database were: Sex, age, time of hospitalization, antithrombotic therapy (warfarin, acenocoumarol, apixaban, dabigatran, edoxaban, rivaroxaban, aspirin, clopidogrel, other antiplatelet agents, low molecular weight heparin, and fondaparinux), diagnosis at discharge and used resources. Basal features are presented as percentage values for categorized variables and as mean +/- SD for categorized once. From January 1st, 2010 to October 6th, 2021, 25132 patients were hospitalized in our department; 4089 (16.27%, mean age 75.59+/-10.82) were discharged with AF diagnosis; of them, 2245 were males (54.81%, mean age 73.56+/-11.45) and 1851 females (45.19%, mean age 78.06+/-9.47). Average length of stay was 5.76+/-4.88 days; 154 patients died and 88 were moved to other Departments/Structures. AF was the main diagnosis in 899 patients (21.94%). The most frequent main diagnosis in patients with AF was acute myocardial infarction (1973 discharges, 48.19%). The most frequent secondary cardiac diagnosis was chronic coronary syndrome (1864 discharges, 45.51%), and the most frequent secondary associated condition was arterial hypertension (1010 discharges, 24.66%). For the analysis of antithrombotic treatments, the final sample included 3067 patients, after excluding in-hospital deaths, transferred out or self-discharged patients, as well as discharges lacking indications for prescribed treatments. OAC treatment increased significantly (35.63% in 2010-2012 vs 61.18% in 2019-2021, +25.55%, P < 0.0001), in spite of any antiplatelet agent use. This rise was due to increasing use of DOACs, with or without antiplatelet agents, from 3.04% in 2013-2015 to 50.06% in 2019-2021 (+47.02%, P < 0.0001) and was greater for factor Xa inhibitors, especially apixaban. In addition, treatment with a vitamin K antagonist, in spite of any antiplatelet agent use, decreased from 35.63% in 2010-2012 to 11.12% in 2019-2021 (-24.48%, P < 0.0001), as well as any antiplatelet therapy, alone or in double combination, (49.18% in 2010-2012 vs 34.18% in 2019-2021, -15.00%, P < 0.0001); and patients not receiving antithrombotic therapy declined with time (14.58% in 2010-2012 vs 1.97% in 2021, P < 0.0001). Real-world patients with AF are elderly and affected by cardiovascular and non-cardiovascular diseases. The percentage of patients on OAT and DOACs increased. These data suggest a slow, gradual guidelines implementation process.

Assessing the Relationship between Thrombosis and Immune-Related Adverse Events in Patients with Lung Cancer Treated with Immune Checkpoint Inhibitors

Introduction: Venous thromboembolisms (VTE) frequently occur in cancer patients, and the role of immune checkpoint inhibitors on thrombotic risk has been a rising concern for clinicians. Identifying pro-thrombotic risk factors could guide primary prophylaxis strategies in patients receiving immunotherapy. Immune checkpoint blockade can induce inflammatory side effects known as immune-related Adverse Events (irAE). Inflammatory states are known to be associated with a hypercoagulable state. It is not established whether patients treated with immunotherapy experience a higher risk of thrombotic events during periods of increased inflammation surrounding irAE occurrence. Similarly, while immune checkpoint inhibitors have been shown to be associated with increased bleeding events, it is not clear whether irAE occurrence affects incidence of hemorrhage. Our primary objective was to determine the association between irAE and thrombosis in patients with non-small cell lung cancer treated with immune checkpoint inhibitors in order to better elucidate potential risk factors for thrombosis in patients on immunotherapy. Our secondary objective was to evaluate the association between irAE and clinically significant bleeding events. Methods: We identified all patients with non-small cell lung cancer treated with pembrolizumab at an academic medical center between 2016 and 2021. Outcomes of interest were VTE and clinically relevant bleeding (a composite of major bleeding and clinically-relevant non-major bleeds). We collected information regarding concurrent chemotherapy use with immunotherapy, frequency and type of irAE, steroid use for treatment for irAE, and use of anticoagulation or antiplatelet agents. We used logistic regression to calculate the odds ratios (OR) and 95% confidence intervals (CI) of VTE and clinically-relevant bleeding among patients who had an irAE prior to the outcome of interest compared to those who did not. We calculated the odds of VTE associated with use of concurrent chemotherapy (vs. no concurrent chemotherapy). Results: Of 102 patients included, 46.1% were female, and average age at diagnosis was 66.8 ± 10.5 years. Thirty-four patients were treated with pembrolizumab alone, with the remainder receiving concurrent chemotherapy and/or targeted therapy with pembrolizumab. Overall, 21 patients experienced thrombotic events (20.6%), 7 (6.9%) experienced clinically-relevant bleeding events, and 28 (27%) experienced an irAE. (Table 1). Overall, occurrence of irAE was not associated with increased odds of VTE (OR: 1.07, 95% CI: 0.37-3.11, P=0.90). (Figure 1). Similarly, among those with an irAE, steroid treatment was not associated with increased odds of VTE (OR: 1.14, 95% CI: 0.17-7.69, P=0.89). The combination of chemotherapy with pembrolizumab did not result in a statistically significant increase in odds of VTE (OR: 1.37, 95% CI: 0.52-3.60, P=0.53). The odds of clinically-relevant bleeding was not statistically higher among those with an irAE (OR: 2.10, 95% CI: 0.44-10.0, P=0.35). Conclusions: The development of irAE in patients with NSCLC treated with pembrolizumab does not appear to predict the development of VTE. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal