Risk Of Arterial Thromboembolism Research Articles

New drugs, old problems: immune checkpoint inhibitors and cancer-associated thrombosis

A frequent side effect of cancer treatment is venous thromboembolism (VTE), which is made more likely by systemic anticancer medication. Immune checkpoint inhibitors (ICIs) have emerged as a paradigm-shifting treatment for many cancers. Early trials investigating the efficacy of ICIs did not identify thrombosis as a significant adverse event of concern. An initial meta-analysis reported a 1.1% [95% confidence interval (CI) 0.5-2.1] risk of arterial thromboembolism (ATE) and a 2.7% (95% CI 1.8-4.0) rate of vein thrombosis. ICIs have, however, been linked to ATE and VTE in an increasing number of post-marketing investigations. The reported incidence rates of cumulative VTE range from 5-8% at 6 months to 10-12% at 12 months, while the rates of ATE vary from 1-2% at 6 months to 17 months. Furthermore, a number of studies show a correlation between reduced survival and ICI-related thromboembolism. In order to provide a compiled and thorough narrative on the mechanisms, incidence, risk factors, and survival related to ICI-associated VTE and ATE, this narrative review summarizes the literature.

In AF, CHA2DS2-VASc 1 subgroups did not differ for predicting risk for arterial thromboembolism at 1 y.

Østergaard L, Olesen JB, Petersen JK, et al. Arterial thromboembolism in patients with atrial fibrillation and CHA2DS2-VASc 1: a nationwide study. Circulation. 2024;149:764-773. 38152890.

Arterial Thromboembolism in Japanese Patients With Cancer: Incidence, Predictors, and Survival Impact

BackgroundThromboembolism is a significant complication for patients with cancer, leading to treatment interruptions and poor outcomes. ObjectivesThe aim of this study was to investigate the incidence of arterial thromboembolism (ATE) within cancer populations, identify the predictors of ATE, and determine its survival impact. MethodsA retrospective multicenter study was performed using data from the Osaka Cancer Registry linked with administrative data from 2010 to 2015. Patients were monitored for 5 years after cancer diagnosis, and ATE incidence was calculated with death as a competing risk. Fine and Gray competing risk regression models and Cox proportional hazards models were used to evaluate the predictors of ATE and the survival impact. Restricted mean survival time (RMST) was used to assess whether antithrombotic therapy after ATE contributed to improved survival. ResultsThe cohort comprised 97,448 patients with cancer (42.3% women, median age 70 years). ATE incidence displayed an annual increase, peaking 1 year after cancer diagnosis (1-, 2-, 3-, 4-, and 5-year cumulative incidences were 1.29%, 1.77%, 2.05%, 2.22%, and 2.32%, respectively). Male sex, advanced age, advanced cancer stage, and hematologic malignancies correlated with a high risk for ATE. Patients with ATE had a 2-fold increased risk for mortality compared with those without ATE. The 90-day and 1-year RMST differences for those on antithrombotic therapy were 13.3 days (95% CI: 10.4-16.2 days; P < 0.001) and 57.8 days (95% CI: 43.1-72.5 days; P < 0.001), favoring the antithrombotic therapy group. The RMST differences varied by cancer stage. ConclusionsThe risk for ATE varies according to sex, age, and cancer progression and type. Antithrombotic therapy after ATE is associated with improved survival among patients with cancer.

Arterial Thromboembolism in Patients With Atrial Fibrillation and CHA2DS2-VASc Score 1: A Nationwide Study.

Oral anticoagulation is suggested in patients with atrial fibrillation and a CHA2DS2-VASc score ≥1 (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, and sex score). To assess granular differences within CHA2DS2-VASc 1, the incidence of arterial thromboembolism according to CHA2DS2-VASc 1 subgroups was examined. The Danish National Patient Registry and the Danish Prescription Registry were linked on a nationwide level to identify patients with atrial fibrillation from 2000 to 2021 without oral anticoagulation and categorized according to CHA2DS2-VASc score: CHA2DS2-VASc 0 (male and female subjects); CHA2DS2-VASc 1 (hypertension, heart failure, diabetes, vascular disease, and age 65-74 years); or CHA2DS2-VASc 2 (age ≥75 years without other risk factors). Female sex was not considered a risk factor in any risk group. The outcome was arterial thromboembolism (ischemic stroke, embolism of extremity, or transient cerebral ischemia). Study groups were compared using Cox regression analysis. We included 26 701 patients with a CHA2DS2-VASc 0 score; 22 915 with CHA2DS2-VASc 1 (1483 patients with heart failure, 9066 with hypertension, 843 with diabetes, 770 with vascular disease, and 10 753 who were 65 to 74 years of age); and 14 525 patients with CHA2DS2-VASc 2 (≥75 years of age without other risk factors). With a median of 1 year of observation time, the cumulative incidence of arterial thromboembolism was 0.6% (n=154 [95% CI, 0.6%-0.8%]), 1.4% (n=16 [95% CI, 0.8%-2.2%]), 1.9% (n=141 [95% CI, 1.6%-2.2%]), 1.7% (n=12 [95% CI, 0.9%-2.9%]), 2.0% (n=13 [95% CI, 1.1%-3.4%]), 2.3% (n=187 [95% CI, 2.0%-2.7%]), and 4.4% (n=533 [95% CI, 4.1%-4.8%]) for CHA2DS2-VASc 0, heart failure, hypertension, diabetes, vascular disease, age 65 to 74 years (CHA2DS2-VASc 1), and age ≥75 years (CHA2DS2-VASc 2), respectively. No statistically significant difference was identified among subgroups of CHA2DS2-VASc 1 (P=0.15 for difference). For patients with atrial fibrillation, all subgroups of CHA2DS2-VASc 1 were associated with lower incidence of arterial thromboembolism compared with age ≥75 years without other risk factors (ie, CHA2DS2-VASc 2) and a higher incidence compared with CHA2DS2-VASc 0. No statistically significant difference was identified between the subgroups of CHA2DS2-VASc 1. These findings support current recommendations that patients within this intermediate risk group could be identified with a similar risk of arterial thromboembolism.

Occurrence and Outcomes of Acute Cerebrovascular Events in Patients with Non-Hodgkin Lymphoma

Background Stroke or Cerebrovascular Accident (CVA) is one of the leading causes of mortality in the world whether it be ischemic or hemorrhagic 1,2. There has been an association of increased incidence of stroke in patients with cancer due to multiple factors 3. Regarding hematologic malignancies, there have been studies to assess the risk of developing stroke in patients with Hodgkin lymphoma (HL), however the information on non-Hodgkin lymphoma (NHL) is limited and not well understood4. We conducted a retrospective case-control study to assess the incidence, risks, and complications and length of stay of patients with current or prior history of NHL who developed an ischemic stroke. Methods This case-control study identified 29,632 patients older than 18 years, with or without CVA and with or without active or history of Non-Hodgkin Lymphoma (NHL) who were admitted to diverse private hospitals between 2018-2022. The patients were divided into two groups, one with current or prior NHL (n=10,699) and a control group of patients (n=18,933) with similar characteristics. Patients with active hemorrhagic stroke, pregnancy, malignancies other than NHL, prior hemorrhagic or ischemic stroke, infective endocarditis, atrial fibrillation, and acute coronary syndrome on admission were excluded. We compared patient's characteristics and the risk of developing a stroke based on the presence or absence of NHL as well as the factors that increased hospital mortality. Length of stay was evaluated as a secondary outcome. Bivariate statistical analysis was used to calculate the odds ratios using RStudio 4.2.2 and JMP Pro 16.0 for all data analysis. Results Of the group with NHL 46.39 % (n=4958) were female, and 53.61% (n=5729) were male, 42% were current or former smokers (n=4497), 27.49% (n=2941) had diabetes, 44.68% (n=4780) had hypertension; 3.34% (357) of them passed away. Of the control group 57.51 % (n=10876) were female, and 42.49% (n=8036) were male, 35% were current or former smokers (n=6763), 16.43% (n=3111) had diabetes, 28.89% (n=5469) had hypertension; 0.47% (n=88) of them passed away. The mean length of stay of patients with stroke was 7.99 days in the NHL group, and 5.99 days in the control group. Regarding the admissions due to stroke, there were 214 patients in the group with NHL, and in the control group where there were 113. Patients with NHL are more likely to have a CVA compared to the control group (OR 2.39 p&amp;lt;0.0001 CI 1.47~3.85) Patients who have NHL are more likely to die (OR=6.08 p&amp;lt;0.001) CI 4.77~7.74) compared to patients without NHL from all causes. Conclusion Patients with Non-Hodgkin lymphoma have an increased risk of developing a stroke compared to patients with similar characteristics but without NHL (or other malignancies). It was also noted that patients had an increased length of stay. Other variables and characteristics of patients that were identified to be more likely to have a CVA and statistically significant for this sample are already well-known risk factors for CVA including diabetes, hypertension, and cardiovascular disease. However, this study aimed to isolate those variables to identify the risk for stroke in this unique population. Our study limitation is the broad spectrum of NHL and possible confounders between the different variants of NHL. More studies are needed to investigate this. References Navi B, Reiner A, Kamel H, et al. Risk of Arterial Thromboembolism in Patients with Cancer. J Am Coll Cardiol. 2017 Aug, 70 (8) 926-938.Turner, M., Murchie, P., Derby, S. et al. Is stroke incidence increased in survivors of adult cancers? A systematic review and meta-analysis. J Cancer Surviv 16, 1414-1448 (2022). https://doi.org/10.1007/s11764-021-01122-7Dardiotis E, Aloizou AM, Markoula S, et al. Cancer-associated stroke: Pathophysiology, detection, and management (Review). Int J Oncol. 2019;54(3):779-796. doi:10.3892/ijo.2019.4669Wei Y, Yang Q, Qin Q, et al. Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study. Eur Neurol. 2020;83(1):41-48. doi:10.1159/000506046

Thrombotic risk of platinum combination chemotherapy with and without immune checkpoint inhibitors for advanced non-small cell lung cancer: a nationwide inpatient database study

ObjectivesTo determine the associated thromboembolism risk with adding immune checkpoint inhibitors (ICI) to platinum combination chemotherapy compared with platinum combination chemotherapy alone in patients with advanced non-small cell lung cancer.Materials and methodsThis study identified 75,807 patients with advanced non-small cell lung cancer from the Japanese Diagnosis Procedure Combination database who started platinum combination chemotherapy between July 2010 and March 2021. The incidence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and all-cause mortality within 6 months after commencing platinum combination chemotherapy was compared between patients receiving chemotherapy with ICI (ICI group, n = 7,177) and without ICI (non-ICI group, n = 37,903). Survival time analysis was performed using the overlap weighting method with propensity scores to adjust for background factors. The subdistribution hazard ratio for developing thromboembolism was calculated using the Fine-Gray model with death as a competing risk. The hazard ratio for all-cause mortality was also calculated using the Cox proportional hazards model.ResultsOverall, VTE and ATE occurred in 761 (1.0%) and 389 (0.51%) patients, respectively; mortality was 11.7%. Propensity score overlap weighting demonstrated that the subdistribution hazard ratio (95% confidence interval) for VTE and ATE in the ICI group was 1.27 (1.01–1.60) and 0.96 (0.67–1.36), respectively, compared with the non-ICI group. The mortality hazard ratio in the ICI group was 0.68 (0.62–0.74).ConclusionThe addition of ICI to platinum combination therapy was associated with a higher risk of VTE compared with platinum combination therapy alone, while the risk of ATE might be comparable.

Risk of admission to hospital with arterial or venous thromboembolism among patients diagnosed in the ambulatory setting with covid-19 compared with influenza: retrospective cohort study

ObjectiveTo measure the 90 day risk of arterial thromboembolism and venous thromboembolism among patients diagnosed with covid-19 in the ambulatory (ie, outpatient, emergency department, or institutional) setting during periods before...

Impact of venous thromboembolism on incidence of arterial thromboembolism - An analysis of German outpatient claims data

BackgroundVenous thromboembolism (VTE) and arterial thromboembolism (ATE) are considered as two separate disease-entities. In recent years, studies have reported clear associations between VTE and atherosclerosis. We aimed to evaluate the long-term risk of ATE in VTE patients in comparison to controls without VTE. MethodsNationwide outpatient claims data of all inhabitants with statutory health insurance in Germany were used for secondary data analysis between the years 2011 and 2020. Patients treated in 2013 were stratified by VTE event, and groups were 1:2-matched by age and sex. The hazard for an ATE event in a 5-year follow-up period between patients with and without VTE was calculated with multivariable Cox regression adjusted for age, sex, cardiovascular risk factors, and comorbidities. ResultsOf 69,699,277 individuals treated in the year 2013 by German physicians in outpatient care, in total 686,382 individuals (age 59.8 ± 17.5 years, 65.4 % females) were included comprising 228,794 patients with VTE and 457,588 controls without VTE. VTE patients more often had cardiovascular risk factors (81.6 % vs. 62.2 %) and traditional VTE risk factors. The occurrence of ATE events during follow-up was 1.8 %-points higher in VTE patients in comparison to the controls (9.7 % vs. 7.9 %). VTE events were independently associated with increased occurrence of ATE events within follow-up (HRadjusted 1.19 [99%CI 1.16–1.23], p < 0.0001). ConclusionsPatients with a VTE event have an increased long-term risk for subsequent arterial cardiovascular events. Large prospective cohorts are needed to identify patient subgroups with a very high ATE risk after VTE.

Arterial and Venous Thromboembolism in ALK-Rearrangement-Positive Non-small Cell Lung Cancer: A Population-Based Cohort Study.

There is scarce data regarding the incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in the molecular subtypes of non-small cell lung cancer (NSCLC). We aimed to investigate the association between Anaplastic Lymphoma Kinase (ALK)-positive NSCLC and thromboembolic events. A retrospective population-based cohort study of the Clalit Health Services database, included patients with NSCLC diagnosed between 2012 and 2019. Patients exposed to ALK-tyrosine-kinase inhibitors (TKIs) were defined as ALK-positive. The outcome was VTE (at any site) or ATE (stroke or myocardial infarction) 6 months prior to the diagnosis of cancer, until 5 years post-diagnosis. The cumulative incidence of VTE and ATE and hazard-ratios (HR) with 95% CIs were calculated (at 6- 12- 24 and 60-months), using death as a competing risk. Cox proportional hazards multivariate regression was performed, with the Fine and Gray correction for competing risks. The study included 4762 patients, of which 155 (3.2%) were ALK-positive. The overall 5-year VTE incidence was 15.7% (95% CI, 14.7-16.6%). ALK-positive patients had a higher VTE risk compared to ALK-negative patients (HR 1.87 [95% CI, 1.31-2.68]) and a 12-month VTE incidence of 17.7% (13.9-22.7%) compared to 9.9% (9.1-10.9%) in ALK-negative patients. The overall 5-year ATE incidence was 7.6% [6.8-8.6%]. ALK positivity was not associated with ATE incidence (HR 1.24 [0.62-2.47]). In this study, we observed a higher VTE risk, but not ATE risk, in patients with ALK-rearranged NSCLC relative to those without ALK rearrangement. Prospective studies are warranted to evaluate thromboprophylaxis in ALK-positive NSCLC.

Tumor Genomic Profile Is Associated With Arterial Thromboembolism Risk inPatients With Solid Cancer.

Patients with cancer have an increased risk for arterial thromboembolism (ATE). Scant data exist about the impact of cancer-specific genomic alterations on the risk for ATE. The aim of this study was to determine whether individual solid tumor somatic genomic alterations influence the incidence of ATE. A retrospective cohort study was conducted using tumor genetic alteration data from adults with solid cancers who underwent Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets testing between 2014 and 2016. The primary outcome, ATE, was defined as myocardial infarction, coronary revascularization, ischemic stroke, peripheral arterial occlusion, or limb revascularization and identified through systematic electronic medical record assessments. Patients were followed from date of tissue-matched blood control accession to first ATE event or death, for up to 1 year. Cause-specific Cox proportional hazards regression was used to determine HRs of ATE for individual genes adjusted for pertinent clinical covariates. Among 11,871 eligible patients, 74% had metastatic disease, and there were 160 ATE events. A significantly increased risk for ATE independent of tumor type was noted for the KRAS oncogene (HR: 1.98; 95% CI: 1.34-2.94; multiplicity-adjusted P=0.015) and the STK11 tumor suppressor gene (HR: 2.51; 95% CI: 1.44-4.38; multiplicity-adjusted P=0.015). In a large genomic tumor-profiling registry of patients with solid cancers, alterations in KRAS and STK11 were associated with an increased risk for ATE independent of cancer type. Further investigation is needed to elucidate the mechanism by which these mutations contribute to ATE in this high-risk population.

Arterial Thromboembolism in Patients With AF and CHA2DS2-VASc Score 0-2 With and Without Cancer

It is unclear whether newly diagnosed cancer adds to the risk of arterial thromboembolism (ATE) in patients with atrial fibrillation/flutter (AF). This is especially relevant for AF patients with low to intermediate CHA2DS2-VASc scores in whom the risk-benefit ratios between ATE and bleeding are delicately balanced. The objectives were to evaluate the ATE risk in AF patients with a CHA2DS2-VASc score of 0 to 2 with and without cancer. A population-based retrospective cohort study was performed. Patients with a CHA2DS2-VASc score of 0 to 2 not receiving anticoagulation at cancer diagnosis (or the matched index date) were included. Patients with embolic ATE or cancer before study index were excluded. AF patients were categorized into AF and cancer and AF and no cancer cohorts. Cohorts were matched for multinomial distribution of age, sex, index year, AF duration, CHA2DS2-VASc score, and low/high/undefined ATE risk cancer. Patients were followed from study index until the primary outcome or death. The primary outcome was acute ATE (ischemic stroke, transient ischemic attack, or systemic ATE) at 12months using International Classification of Diseases-Ninth Revision codes from hospitalization. The Fine-Gray competing risk model was used to estimate the HR for ATE with death as a competing risk. The 12-month cumulative incidence of ATE was 2.13% (95% CI: 1.47-2.99) in 1,411 AF patients with cancer and 0.8% (95% CI: 0.56-1.10) in 4,233 AF patients without cancer (HR: 2.70; 95% CI: 1.65-4.41). The risk was highest in men with CHA2DS2-VASc=1 and women with CHA2DS2-VASc=2 (HR: 6.07; 95% CI: 2.45-15.01). In AF patients with CHA2DS2-VASc scores of 0 to 2, newly diagnosed cancer is associated with an increased incidence of stroke, transient ischemic attack, or systemic ATE compared with matched controls without cancer.

Thromboembolism profiles associated with cyclin-dependent kinase 4/6 inhibitors: a real-world pharmacovigilance study and a systematic review

ABSTRACT Background Thrombosis is the second leading cause of mortality in cancer patients. This study aimed to investigate the association between cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and thrombosis. Research design and methods A retrospective pharmacovigilance analysis based on real-world data combined with a systematic review was used to explore the thrombotic risk profiles of CDK4/6i. The study has been registered with Prospero (CRD42021284218). Result In the pharmacovigilance analysis, CDK4/6i showed a higher rate of reported venous thromboembolism (VTE) (ROR = 2.78, 95% CI = 2.64–2.92), with the highest signal for trilaciclib (ROR = 27.55, 95% CI = 13.43–56.52) but only 9 cases, followed by abemaciclib (ROR = 3.73, 95% CI = 3.19–4.37). For arterial thromboembolism (ATE), only ribociclib increased the reporting rate (ROR = 2.14, 95% CI = 1.91–2.41). In the meta-analysis, palbociclib, abemaciclib, and trilaciclib all increased the risk of VTE (OR = 2.23, 3.17, and 3.90). In the subgroup analysis, only abemaciclib increased the risk of ATE (OR = 2.11, 95% CI = 1.12–3.99) . Conclusions CDK4/6i had different profiles of thromboembolism. Palbociclib, abemaciclib, or trilaciclib increased the risk of VTE. Ribociclib and abemaciclib showed a weak association with the risk of ATE.

Thrombotic and bleeding outcomes following the perioperative interruption of anticoagulation among patients with nonvalvular atrial fibrillation and active cancer

BackgroundPatients with cancer are at an increased risk of developing atrial fibrillation (AF) and often need to undergo procedures or surgery that requires periprocedural interruption of anticoagulation. Anticoagulated patients with cancer might be at increased risk of postprocedural thromboembolic and bleeding complications. Data on postprocedural outcomes among patients with concurrent active cancer and AF are sparse. ObjectiveTo assess the 30-day risk of postoperative thromboembolic and major bleeding complications after the periprocedural interruption of anticoagulation among patients with AF and active cancer. MethodsWe conducted a single-center retrospective cohort study in patients with active cancer and AF who required periprocedural interruption of anticoagulation for invasive procedures between August 2015 and May 2019. The primary endpoints were the 30-day postoperative risks of arterial thromboembolism (ATE) and major bleeding. The secondary endpoints included the 30-day risks of venous thromboembolism, clinically relevant nonmajor bleeding, and overall mortality. ResultsTwo hundred sixty-four patients undergoing 302 periprocedural interruptions were included in our study. The 30-day risk of ATE was 0.7% (95% CI, 0.1%-2.4%), and the 30-day risk of major bleeding was 1.7% (95% CI, 0.6%-3.9%). The 30-day risks of venous thromboembolism and clinically relevant nonmajor bleeding were 0.7% (95% CI, 0.1%-2.4%) and 4.3% (95% CI, 2.5%-7.3%), respectively. The overall risk of mortality at 30 days was 1.3% (95% CI, 0.4%-3.4%). There was one fatal postoperative stroke. ConclusionsPatients with AF and active cancer in this study were at relatively low risk for ATE and postoperative bleeding complications when patients were managed according to commonly applied perioperative management recommendations.

Anticoagulation and/or Antiplatelet in Thrombotic Antiphospholipid Syndrome with Previous Arterial Thromboembolism: A Retrospective Cohort

Introduction: Thrombotic antiphospholipid syndrome (TAPS) is a prothrombotic autoimmune disease associated with a high risk of arterial thromboembolism (ATE). While direct oral anticoagulants (DOAC) are inferior treatment in TAPS with ATE, the optimal antithrombotic regimen of vitamin K antagonists (VKA) and/or antiplatelet therapy (AP) remains unclear. Objectives: To assess the effectiveness and safety of VKA (target (t) international normalized ratio (INR) 2-3), VKA (t INR 2-3) with AP (including dual AP therapy), VKA (t INR >3), VKA (t INR >3) with AP, and AP alone at preventing recurrent thrombotic events in TAPS patients with previous ATE. Methods: This retrospective cohort study included adult TAPS patients with previous ATE assessed at two academic tertiary care centers in Toronto, Canada between April 1, 2011 to April 1, 2021. Included patients met Sydney criteria for TAPS and had a history of ATE (ischemic stroke (IS), transient ischemic attack (TIA), myocardial infarction (MI), or systemic embolism (SE)). At participating centers, patients with a thrombotic history suspicious for TAPS were screened for lupus anticoagulant, anti-cardiolipin antibodies, and/or anti-beta-2-glycoprotein 1 antibodies (anti-B2GP1) at the discretion of the treating physician. Testing for anti-B2GP1 was only available as a send away test. We excluded patients with a known cardioembolic source for their ATE including atrial fibrillation, patent foramen ovale, mechanical heart valves, Libman-Sacks endocarditis, those with initial ATE associated with catastrophic antiphospholipid syndrome (CAPS), and those treated with DOAC. Outcomes included both thrombotic and bleeding events. Recurrent thrombosis included both ATE and VTE. ATE included IS, TIA, MI, or SE. Bleeding events were categorized as major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) as defined by International Society on Thrombosis and Haemostasis criteria. Outcomes were assessed during the time the particular antithrombotic regimen was used. If a single patient had multiple antithrombotic regimens, they were included in multiple groups for the time they used that particular antithrombotic regimen, defined as antithrombotic trials. Outcomes were calculated as the number of events per 100 patient years by antithrombotic regimen with 95% confidence intervals (CI) using Poisson's exact test. Statistical calculations were performed using SPSS. Results: From an initial 891 patients with at least one positive antiphospholipid antibody test, 120 patients met criteria for TAPS and had a previous ATE. 62 patients were excluded for the following reasons: 47 for a cardio-embolic source of ATE, 5 for absence of any follow up, 7 for use of DOAC, and 3 for CAPS in the absence of any other ATE. After exclusions, 58 patients with a total of 89 antithrombotic trials were included in the analysis with a cumulative follow up of 248.4 years. The study population comprised of thirty-one (53.4%) women with a mean age of 51 (Standard Deviation (SD) 12.9) years at the start of their initial antithrombotic trial. Twenty-three (39.7%) patients were known to have systemic lupus erythematosus (SLE) whereas seven (12.1%) patients had non-SLE autoimmune disorders. Thirty-four (58.6%) patients had baseline hypertension. The baseline characteristics are summarized in table 1. Overall, there were a total of 7 ATE and 1 VTE recurrences with a thrombotic rate of 3.2 per 100 patient-years (95% CI 1.4 to 6.3). The recurrence rates in the VKA (t INR 2-3), VKA (t INR 2-3) with AP, VKA (t INR >3) with AP, and AP alone were 3.3 (95% CI 0.9 to 8.4), 2.6 (95% CI 0.3 to 9.3), 0 (95% CI 0 to 18.8), and 6.8 (0.8 to 24.4) per 100 patient-years respectively. There were a total of 10 MB events including 4 intracranial bleeding (ICB), 1 gastrointestinal bleeding, and 5 other types of MB. ICB occurred in 3 patients on VKA (t INR 2-3) and 1 on VKA (t INR 2-3) with AP. Outcomes are summarized in table 2. Conclusions: This retrospective cohort of 58 patients with TAPS and a previous ATE demonstrated a numerically higher risk of recurrent thrombosis with AP alone and a numerically higher risk of MB with the combination VKA and AP. Study limitations include the small sample size, risk of selection bias, and retrospective design. Larger, prospective studies are needed to confirm our observations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Arterial Thromboembolism in Cancer Patients Treated with Apixaban

Introduction: Arterial thromboembolism is a rising concern in patients with cancer. Data considering incidence and risk factors are scarce. Here we describe arterial thrombosis in a cohort of cancer patients receiving apixaban as treatment for venous thromboembolism. Methods: A total of 298 cancer patients with any type of venous thromboembolism were treated up to 6 months with apixaban 5 mg twice daily. After six months, the 196 patients left in the study further received secondary prophylaxis with apixaban 2.5 mg twice daily for up to 30 months. Primary efficacy outcome was recurrent venous thromboembolism and safety outcome was bleeding. Arterial thromboembolism was registered as a serious adverse event during the whole study period. This is a post-hoc analysis of the arterial events. Results: Arterial events were registered in 16/298 (5.4 %, CI: 3.1-8.6) patients. Leucocyte count at baseline were higher (p=0.006) in patients with arterial thromboembolism compared to patients without arterial thromboembolism. Factors that increased the risk of arterial thromboembolism in our patient cohort was pancreatic cancer (OR: 11.41 (95 % CI: 3.81-34.17)), ovarian cancer (OR: 20 (95 % CI: 2.62-152.61)), BMI <22.3 (OR: 3.14 (95 % CI: 1.12-8.79)) and previous venous thromboembolism (OR: 4.673 (1.503-14.524)). Patients with pancreatic cancer had a much higher frequency of arterial thromboembolism than other cancers (figure 1). During the first 6 months, 7/25 (28 %, CI: 12-49)) patients with pancreatic cancer had a stroke. Among pancreatic cancer patients, d-dimer at baseline was higher in those who experienced arterial thromboembolism compared to those who did not (p=0.037). Conclusion: In our cohort of cancer patients treated for venous thromboembolism with apixaban, there seems to be an increased risk of arterial thromboembolism in patients with pancreatic cancer, low BMI and previous venous thromboembolism. High leukocyte count may be a biomarker for increased risk of arterial thrombosis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Arterial Thromboembolism Is Prevalent and Often Suboptimally Managed in Immune Thrombocytopenia

Background: Adults with chronic immune thrombocytopenia (ITP) have increased risk of arterial thromboembolism (TE) compared to the general population. Adequate therapy with antiplatelets, anticoagulants or revascularization may be limited by thrombocytopenia and bleeding risk. Few studies have examined the quality of arterial TE management in ITP, and outcomes such as bleeding and cardiovascular deaths. Aims: To examine acute inpatient management and outcomes of arterial TE in relapsed/refractory ITP. Methods: This multicentre retrospective cohort study included all chronic ITP patients ≥18 years who received second-line therapy (2012-2020) in the province of Alberta, Canada. Demographics, ITP disease characteristics, traditional vascular risk factors, and history of TE were collected. We also collected ITP-related thrombotic risk factors including splenectomy status, antiphospholipid antibody syndrome (APS), and use of thrombopoietin receptor agonists (TPO-RA) at the time of TE. The incidence rate was calculated by dividing the number of TE events by the person-years of follow-up since ITP diagnosis. For each TE event, we examined the initial and nadir platelet counts, acute ITP-directed therapy, and quality of TE management (antiplatelets, anticoagulants, revascularization) during hospitalization. We assessed outcomes including 30-day mortality, cardiovascular deaths, and bleeding from TE event to last follow-up or death. Research ethics approval was obtained. Results: During 2713 person-years of follow-up since ITP diagnosis, 46/329 patients (14%) developed a total of 53 incident arterial TE events, 9 of whom also developed venous thromboembolism. TE events included 27 (51%) acute coronary syndromes (ACS), 25 (47%) ischemic strokes or transient ischemic attacks (TIA), and 1 (2%) acute limb ischemia. The incidence rate of arterial TE was 2.0 (95% CI 1.5-2.6) per 100 person-years. The median age at time of arterial TE was 67 years (IQR 61-77), 22 (42%) were men (Table 1). Risk factors for arterial TE included: history of atherosclerotic disease (18; 34%), 3 or more traditional vascular risk factors (17; 32%), post-splenectomy status (23; 43%), concurrent TPO-RA use (16; 30%), and APS (5; 9%). Most (37; 70%) were not on antiplatelets or anticoagulants at presentation. Of these, 7 had interruption or discontinuation of prior antiplatelets/anticoagulants due to bleeding risk, and subsequently developed ischemic stroke/TIA. A platelet count <50 x 109/L was observed in 21 (40%) arterial TE events throughout hospitalization. Acute ITP therapies to maintain platelet >50 x 109/L included: IVIG (9/21; 43%), platelet transfusions (7; 33%), TPO-RA (6; 29%), corticosteroids (4; 19%), and rituximab (4; 19%). Of the 27 ACS events, over half (15; 56%) underwent revascularization with either PCI (5 bare metal stents, 6 drug-eluting stents, 1 catheter-directed thrombolysis) or coronary artery bypass graft (3). Patients with platelet count >50 x 109/L showed a non-significant trend towards higher likelihood of revascularization (10/15, 67%) compared to those with platelet count <50 x 109/L (5/11, 45%; P=0.28). Three patients received neither antiplatelets nor revascularization due to severe thrombocytopenia (<30 x 109/L). Of the 25 stroke/TIA events, 6 (24%) underwent revascularization. Antiplatelet or anticoagulants were not offered in 5 cases, mostly due to thrombocytopenia and/or hemorrhagic transformation. At last follow-up, 26/46 (57%) patients died at a median age of 74 (IQR 64-80) years, from cardiovascular deaths (n=10), other TE (n=2), infection (n=7), bleeding (n=1) and other causes (n=6). The 30-day mortality following TE was 10%. Major bleeding occurred in 6 (11%) individuals, at a median of 18 days (IQR 14-32) after TE. Conclusion: Patients with chronic ITP receive suboptimal management of arterial TE including a lower likelihood of receiving antiplatelet/anticoagulants or revascularization. With the advent of newer lines of ITP therapies including three TPO-RAs and fostamatinib, aggressive ITP control is critical to avoid withholding antiplatelet/anticoagulants, and to reduce the risk of bleeding, recurrent TE, and cardiovascular deaths. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk of arterial thromboembolism in patients with concomitant atrial fibrillation and cancer: a systematic review and meta-analysis

Abstract Background/Introduction Atrial fibrillation (AF) and cancer often co-exist and have been independently associated with increased risk of arterial thromboembolism (TE), all cause death and bleeding; however, no cumulative data exist regarding the clinical course of AF patients with comorbid cancer. Purpose The aim of this systematic review and meta-analysis is to synthesize the available data regarding the incidence of major adverse cardiovascular events in AF patients in association with concurrent cancer. Methods The composite outcome of any TE (ischemic stroke, transient ischemic attack, or arterial thrombosis) was defined as the primary study outcome, while all-cause mortality and major or clinically relevant non-major bleeding occurrence as the secondary ones. Literature search was conducted in PubMed (MEDLINE), WebOfScience, Scopus, CENTRAL, OpenGrey, and EThOS databases. A random-effects model meta-analysis was performed. Subgroup analyses were conducted assessing the effect of active cancer history and various cancer subtypes on the outcomes of interest. Meta-regression analyses were also performed to examine the relative impact of CHA2DS2VASC and HASBLED prognostic scores on the risk of TE and bleeding, respectively. Results Overall 17 studies were included in our analysis, encompassing a total of 3,151,861 AF patients. Comorbid cancer was non-significantly associated with lower odds of TE than AF alone (pooled odds ratio (pOR) = 0.85, 95% confidence interval (CI): 0.69–1.03, I2=87%). The likelihood for all-cause death and bleeding occurrence was significantly higher in AF patients with cancer (pOR = 2.27, 95% CI: 1.69–3.06, I2=99%); pOR = 1.58, 95% CI: 1.26–1.97, I2=97% respectively) compared to those without cancer. Subgroup analysis on active cancer status did not yield any substantial difference, marginally improving the heterogeneity of our analysis. The highest all-cause mortality likelihood was observed in Liver-Pancreas-Gallbladder category (pOR = 10.58, 95% CI: 4.69–23.88, I2=98%) while the highest bleeding likelihood was encountered in Genitourinary cancer (pOR = 1.90, 95% CI: 1.42–2.55, I2=71.9%). The performed meta-regression analyses did not yield any significant results. Conclusions Our meta-analysis of 17 eligible studies demonstrated that cancer does not seem to be associated with increased risk of TE, while with increased all-cause death and bleeding occurrence in AF patients. This correlation might be explained by higher cancer-driven mortality rates (competing risk), many cases of TE being left undiagnosed within the scope of palliative cancer care, misdiagnosed episodes of TE due to the presence of brain metastases, optimal cardio-oncology monitoring, and more frequent usage of prophylactic anticoagulation treatment for cancer-associated venous thromboembolism. Nonetheless, further competing-risk survival analyses are warranted before reaching definite conclusions. Funding Acknowledgement Type of funding sources: None.

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40–59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756–0.797; validation AUC 0.766, 0.741–0.790). The validation cohort was stratified as low-risk (score 0–8), intermediate-risk (score 9–13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

Association of COVID-19 vs Influenza With Risk of Arterial and Venous Thrombotic Events Among Hospitalized Patients

The incidence of arterial thromboembolism and venous thromboembolism in persons with COVID-19 remains unclear. To measure the 90-day risk of arterial thromboembolism and venous thromboembolism in patients hospitalized with COVID-19 before or during COVID-19 vaccine availability vs patients hospitalized with influenza. Retrospective cohort study of 41 443 patients hospitalized with COVID-19 before vaccine availability (April-November 2020), 44 194 patients hospitalized with COVID-19 during vaccine availability (December 2020-May 2021), and 8269 patients hospitalized with influenza (October 2018-April 2019) in the US Food and Drug Administration Sentinel System (data from 2 national health insurers and 4 regional integrated health systems). COVID-19 or influenza (identified by hospital diagnosis or nucleic acid test). Hospital diagnosis of arterial thromboembolism (acute myocardial infarction or ischemic stroke) and venous thromboembolism (deep vein thrombosis or pulmonary embolism) within 90 days. Outcomes were ascertained through July 2019 for patients with influenza and through August 2021 for patients with COVID-19. Propensity scores with fine stratification were developed to account for differences between the influenza and COVID-19 cohorts. Weighted Cox regression was used to estimate the adjusted hazard ratios (HRs) for outcomes during each COVID-19 vaccine availability period vs the influenza period. A total of 85 637 patients with COVID-19 (mean age, 72 [SD, 13.0] years; 50.5% were male) and 8269 with influenza (mean age, 72 [SD, 13.3] years; 45.0% were male) were included. The 90-day absolute risk of arterial thromboembolism was 14.4% (95% CI, 13.6%-15.2%) in patients with influenza vs 15.8% (95% CI, 15.5%-16.2%) in patients with COVID-19 before vaccine availability (risk difference, 1.4% [95% CI, 1.0%-2.3%]) and 16.3% (95% CI, 16.0%-16.6%) in patients with COVID-19 during vaccine availability (risk difference, 1.9% [95% CI, 1.1%-2.7%]). Compared with patients with influenza, the risk of arterial thromboembolism was not significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.04 [95% CI, 0.97-1.11]) or during vaccine availability (adjusted HR, 1.07 [95% CI, 1.00-1.14]). The 90-day absolute risk of venous thromboembolism was 5.3% (95% CI, 4.9%-5.8%) in patients with influenza vs 9.5% (95% CI, 9.2%-9.7%) in patients with COVID-19 before vaccine availability (risk difference, 4.1% [95% CI, 3.6%-4.7%]) and 10.9% (95% CI, 10.6%-11.1%) in patients with COVID-19 during vaccine availability (risk difference, 5.5% [95% CI, 5.0%-6.1%]). Compared with patients with influenza, the risk of venous thromboembolism was significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.60 [95% CI, 1.43-1.79]) and during vaccine availability (adjusted HR, 1.89 [95% CI, 1.68-2.12]). Based on data from a US public health surveillance system, hospitalization with COVID-19 before and during vaccine availability, vs hospitalization with influenza in 2018-2019, was significantly associated with a higher risk of venous thromboembolism within 90 days, but there was no significant difference in the risk of arterial thromboembolism within 90 days.

Maximum time between cardiac cycles in atrial fibrillation for assessing the risk of arterial thromboembolism

Aim. To assess the development of thromboembolic events in different types of atrial fibrillation (AF), which differ in the maximum time between cardiac cycles.Material and methods. The main group included 80 patients with permanent AF, while the control one — 88 people without AF. The following investigations were performed: echocardiography, 24-hour electrocardiographic (ECG) monitoring; ultrasound of extracranial arteries, aortic branches, lower limb arteries; sphygmography of the common carotid and posterior tibial arteries. If required, coronary angiography, cerebral angiography, brain computed tomography were performed. According to 24-hour ECG monitoring, all patients of the main group were divided into 2 subgroups (A and B) depending on the maximum time between cardiac cycles in AF: subgroup A (n=42) — patients with a maximum time between cardiac cycles &lt;1,5 seconds, subgroup B (n=38) — ≥1,5. The followup period lasted 1 year. During the follow-up period, the development of arterial thromboembolic events was analyzed.Results. The patients were comparable in key paraclinical characteristics and comorbidity profile. One-year follow-up period revealed a significantly higher incidence of stroke, transient ischemic attack, myocardial infarction, and distal arterial embolism of lower limb arteries in subgroup B. With an increase in the maximum time between cardiac cycles in AF, an increase in hemodynamic parameters of arterial vessels occurred as both proximal and distal arteries. A similar trend was also observed in the analysis of arterial kinetic parameters.Conclusion. Not only the fact of AF presence is important for assessing the risk of arterial thromboembolism, but also its features. The most unfavorable for prognosis is AF with a maximum time between cardiac cycles ≥1,5 seconds. An increase in intra-arterial hemodynamic parameters after a long pause between ventricular contractions in AF without intracardiac thrombosis can become a key factor in the development of complications with existing plaques, which can become a source of distal embolism.