Risk Of Arterial Thromboembolic Events Research Articles

Association of immune checkpoint inhibitors therapy with arterial thromboembolic events in cancer patients: A retrospective cohort study.

Immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for various malignancies. However, research indicates blocking the immune checkpoint pathway may exacerbate atherosclerotic lesions. We aimed to investigate whether ICI therapy increases the risk of arterial thromboembolic events (ATEs). A retrospective cohort study was conducted on patients with histologically confirmed cancer at our institution between 2018 and 2021, using the propensity score matching method. The primary endpoint was ATEs occurrence, comprising acute coronary syndrome, stroke/transient ischemic attack, and peripheral arterial thromboembolism. Subgroup analyses assessed whether the ICI treatment effect on ATEs varied over time by limiting the maximum follow-up duration. Logistic regression analysis identified ATE risk factors in ICI-treated patients. Overall, the ICI group (n = 2877) demonstrated an ATEs risk 2.01 times higher than the non-ICI group (RR, 2.01 [95% CI (1.61-2.51)]; p < 0.001). Subgroup analysis revealed no significant increase in ATEs risk for ICI-treated patients within 1 year (Limited to a max 9-month follow-up, p = 0.075). However, ATEs risk in the ICI group rose by 41% at 1 year (p = 0.010) and 97% at 4 years (p ≤ 0.001). Age, diabetes, hypertension, peripheral atherosclerosis, atrial fibrillation, chronic ischemic heart disease, distant cancer metastasis, and ICI treatment cycles contributed to ATEs risk elevation in ICI-treated patients. ICI-treated patients may exhibit a higher risk of ATEs, especially after 1 year of treatment.

Atherosclerotic cardiovascular diseases in inflammatory bowel diseases: to the heart of the issue.

Atherosclerotic cardiovascular disease and stroke are the leading causes of morbidity and mortality worldwide. Along to the traditional risk factors for these diseases, chronic inflammation is known to be an important player in accelerating the process of atherosclerosis, which can result in an increased incidence of arterial thromboembolic events. As in other chronic inflammatory diseases, in the past few years, several studies suggested that subjects affected by inflammatory bowel diseases (IBD) may also be at an incremented risk of atherosclerotic disease, especially during the periods of disease's flare. Therefore, IBD treatment may assume an important role for achieving both disease remission and the control of the atherosclerotic risk. In this article we aimed to perform a comprehensive review on evidence on the increased risk of arterial thromboembolic events in patients affected by IBD and discuss the potential role of IBD therapy in reducing this risk.

Risk for Arterial Thromboembolic Events (ATEs) in Patients with Advanced Urinary Tract Cancer (aUTC) Treated with First-Line Chemotherapy: Single-Center, Observational Study.

Arterial thromboembolism has been associated with cancer or its treatment. Unlike venous thromboembolism, the incidence and risk factors have not been extensively studied. Here, we investigated the incidence of arterial thromboembolic events (ATEs) in an institutional series of advanced urinary tract cancer (aUTC) treated with cytotoxic chemotherapy. The ATE definition included peripheral arterial embolism/thrombosis, ischemic stroke and coronary events. A total of 354 aUTC patients were analyzed. Most patients (95.2%) received platinum-based chemotherapy. A total of 12 patients (3.4%) suffered an ATE within a median time of 3.6 months from the start of chemotherapy. The most frequent ATE was ischemic stroke (n = 7). Two ATEs were fatal. The 6-month and 24-month incidence were 2.1% (95% confidence interval [CI]: 0.9–4.1) and 3.6% (95% CI: 1.9–6.2), respectively. Perioperative chemotherapy increased the risk for ATE by 5.55-fold. Tumors other than UTC and pure non-transitional cell carcinoma histology were also independent risk factors. No association with the type of chemotherapy was found. Overall, ATEs occur in 4.6% of aUTC patients treated with chemotherapy and represent a clinically relevant manifestation. Perioperative chemotherapy significantly increases the risk for ATE. The role of prophylaxis in high-risk groups should be prospectively studied.

Prevalence and Clinical Significance of Antiphospholipid Antibodies in Hospitalized Patients With COVID-19 Infection.

Background: Coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of arterial thromboembolic events (ATE) and venous thromboembolic events (VTE). Hypercoagulability associated with COVID-19 infection is multifactorial, and underlying pathogenic mechanisms potentially responsible for thrombosis include inflammation resulting in endothelial damage, platelet activation and the presence of antiphospholipid antibodies (APAs). Antiphospholipid antibody syndrome is one of the very few causes which is associated with venous and arterial thromboembolic events. COVID-19 patients have a high prevalence of APAs as well as both ATE and VTE, but their clinical significance in COVID-19 patients is not fully understood yet.Objectives: In this study, we intend to find the prevalence of APAs in hospitalized COVID-19 patients at the time of diagnosis and determine whether their presence has any clinical significance.Methods: This is a retrospective single-institution study involving patients hospitalized for the management of COVID-19 infection at The University of Toledo Medical Center. After obtaining approval from the biomedical institutional review board at The University of Toledo, antiphospholipid antibody (APA) testing was done on pre-stored blood samples of these patients and hospital charts were reviewed till six months from the positive COVID-19 test result. Two groups were created based on the patients' APA testing results (APA positive and APA negative) and used for statistical comparison. Any patients with positive lupus anticoagulant (LA) or abnormal titers APA antibodies were labeled as positive. Demographic data, prognostic outcomes and laboratory values were compared either using Mann-Whitney U-test for continuous variables or Fisher’s exact test for categorical variables.Results: The prevalence of APAs in hospitalized COVID-19 patients at the time of diagnosis was 39.3% in this study. There was no difference in demographic variables between the APA-positive and APA-negative groups. The prevalence of APAs was higher in smokers, where 91% of the APA-positive patients were smokers. There was no statistically significant difference in prognostic outcomes including six-month mortality between APA-positive and APA-negative patients. The comorbidity profile was the same in the two groups. APA-positive patients were found to have lower nadir of absolute lymphocyte count and higher nadir levels of C-reactive protein during hospitalization.Conclusions: The prevalence of APA positivity in hospitalized COVID-19 patients is higher in our study than in historical studies involving non-COVID-19 hospitalized patients, particularly in smokers. However, there is no correlation between APA positivity and prognostic outcomes including six-month mortality. At this point, it is unclear whether APAs are just bystanders or have a pathogenic role. Routine testing of APA in COVID-19 patients is not indicated. Further prospective studies to elucidate the persistence and clinical implications of APAs are needed.

Comparison of risks of arterial thromboembolic events and glaucoma with ranibizumab and aflibercept intravitreous injection: A nationwide population-based cohort study.

To compare intravitreal aflibercept injection with intravitreal ranibizumab injection for the risk of major arterial thromboembolic events (ATEs) and glaucoma. This retrospective, nationwide cohort study investigated 15 611 and 3867 patients aged >50 years with at least one pharmacy claim for intravitreal ranibizumab injection and aflibercept injection between 2011 and 2016, respectively. The inverse probability of treatment weighting method was performed to adjust the baseline difference between the two groups and the hazard risk of adverse events was estimated using the Cox proportional regression model. No significant difference was noted between intravitreal ranibizumab and aflibercept injection for arterial thromboembolic risk, including ischemic stroke and acute myocardial infarction, during a 2-year follow-up (adjusted hazard ratio (HR): 0.87, 95% confidence interval (CI): 0.53-1.42; P = .583). Subgroup analyses revealed that patients age >65 years (adjusted HR: 0.64, 95% CI: 0.45-0.92) and those without coronary artery disease (adjusted HR: 0.59, 95% CI: 0.37-0.95) had significantly lower arterial thromboembolic risk in the aflibercept group than in the ranibizumab group. Additionally, the risk of glaucoma development after intravitreal injection did not significantly differ between the two groups (adjusted HR: 0.63, 95% CI: 0.37-1.06; P = .084). No significant differences in the risk of major ATEs and glaucoma were found between ranibizumab and aflibercept, and aflibercept might be safe for use in elderly patients.

Differential Presentations of Arterial Thromboembolic Events Between Venous Thromboembolism and Atrial Fibrillation Patients.

Objective: Atrial fibrillation (AF) and venous thromboembolism (VTE) share several risk factors related to arterial thromboembolism. No study has reported the differential contribution to arterial thromboembolic events and mortality between these two conditions in the same population. We therefore assessed the differential arterial thromboembolic events between AF and VTE.Methods: We included AF and VTE national cohorts derived from Taiwan National Health Insurance Research Database between 2001 and 2013. The eligible population was 314,861 patients in the AF cohort and 41,102 patients in the VTE cohort. The primary outcome was arterial thromboembolic events, including ischemic stroke, extracranial arterial thromboembolism (ECATE) and myocardial infarction (MI). Secondary outcomes were all-cause mortality and cardiovascular death.Results: After a 1:1 propensity matching, 32,688 patients in either group were analyzed. The risk of arterial thromboembolic events was lower in the VTE cohort than that in the AF cohort (subdistribution hazard ratio [SHR], 0.60; 95% confidence interval [CI], 0.57–0.62). The risk of ischemic stroke (SHR, 0.44; 95% CI, 0.42–0.46) and MI (SHR, 0.80; 95% CI, 0.72–0.89) were lower in the VTE cohort, while the risk of ECATE (SHR, 1.23; 95% CI, 1.14–1.33; particularly lower extremities) was higher in the VTE cohort. All-cause mortality rate was higher in the VTE cohort (HR, 1.18; 95% CI, 1.15–1.21) while the risk of cardiovascular death was lower in the VTE cohort (HR, 0.96; 95% CI, 0.93–0.995).Conclusions: Patients with AF had higher risks of arterial thromboembolic events compared to patients with VTE, despite having risk factors in common. The VTE cohort had higher risks of all-cause mortality and ECATE, particularly lower extremity events, compared to AF patients. The differential manifestations of thromboembolism sequelae and mortality between AF and VTE patients merit further investigation.

A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT.

Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias. The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding. A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat. The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine. Adults with significant upper or lower gastrointestinal bleeding (n = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery. Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo. The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit. A total of 12,009 patients were allocated to receive tranexamic acid (n = 5994, 49.9%) or the matching placebo (n = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid. Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding. These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes. Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid. Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.

Comparative Risk of Arterial Thromboembolic Events Between Aflibercept and Ranibizumab in Patients with Maculopathy: A Population-Based Retrospective Cohort Study

The increasing numbers of elderly patients and rising incidence of maculopathy raise concerns over arterial thromboembolic events (ATEs) with the use of intravitreal anti-vascular endothelial growth factor (VEGF) medications. This study aimed to compare the risk of ATEs between aflibercept and ranibizumab for maculopathy. We conducted a retrospective population-based cohort study analyzing Taiwan's National Health Insurance Database during 2011-2017 to identify patients with maculopathy receiving intravitreal aflibercept or ranibizumab. The primary outcome was any hospitalization or emergency room visit because of ATEs, including ischemic heart disease (IHD), ischemic stroke (IS), and transient ischemic attack (TIA). The secondary outcome was mortality within 30 days after occurrence of ATE. We employed propensity score methods to generate more homogeneous groups for comparison. We included 5791 aflibercept users and 14,534 ranibizumab users in this study. Compared with the ranibizumab group, the aflibercept group was associated with a lower risk of ATE (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.80-0.91), with HRs of 0.86 for IHD (95% CI 0.80-0.93), 0.87 for IS (95% CI 0.76-1.00), and 0.57 for TIA (95% CI 0.46-0.71). The risk of 30-day mortality after ATE (HR 1.39; 95% CI 0.80-2.43) and the risk of all-cause mortality (HR 1.02; 95% CI 0.89-1.17) in the aflibercept group was similar to that in the ranibizumab group. The use of aflibercept in patients with maculopathy was associated with a lower risk of ATE than was the use of ranibizumab. There was no difference in mortality risk between the two groups. Our study could provide strong grounds for future prospective studies to confirm the findings.

Cardiovascular events in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors in Taiwan: a nationwide population-based study.

New-generation breakpoint cluster region-Abelson tyrosine kinase inhibitors (TKIs) have a higher incidence of cardiovascular events than imatinib in patients with chronic myeloid leukaemia (CML). However, this knowledge is insufficiently proven. Hence, this study aimed to explore the association between cardiovascular events and TKIs in patients with CML. This retrospective population-based cohort study enrolled first-time users of imatinib, dasatinib, and nilotinib between 1 January 2007 and 31 December 2016. Arterial thromboembolic events (ATEs) were the primary outcome, while other cardiovascular-related events were the secondary outcomes. The event rates were estimated using Kaplan-Meier estimates, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Additionally, the competing risk was adjusted using the Fine and Gray competing risk model. We included 1207 patients. Nilotinib had a significantly higher ATE risk (subdistribution HR = 4.92, 95% CI = 1.68-14.36) than imatinib. Conversely, no difference was found for other cardiovascular-related events. Risks of ATE and other cardiovascular-related events were similar between dasatinib and imatinib and between nilotinib and dasatinib. The risk of ATE hospitalization consistently increased throughout the main analyses and sensitivity analyses. Nilotinib-treated patients had a significantly higher risk of developing ATE than imatinib-treated patients. However, the risks of ATE and other cardiovascular-related events were not significantly different between dasatinib and imatinib.

First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland

Reports of ChAdOx1 vaccine–associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0–27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41–13.83), with an estimated incidence of 1.13 (0.62–1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29–3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12–1.34) 0–27 d after vaccination, with an SCCS RR of 0.97 (0.93–1.02). For hemorrhagic events 0–27 d after vaccination, the aRR was 1.48 (1.12–1.96), with an SCCS RR of 0.95 (0.82–1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.

The risk of arterial thrombosis in carriers of natural coagulation inhibitors: a prospective family cohort study

BackgroundWhether the carriership of inherited antithrombin (AT), protein C (PC), and protein S (PS) deficiency increases the risk of arterial thromboembolic events (ATE) is controversial. This information has the potential to inform the management of family members of probands with inherited deficiency of natural anticoagulants.Patients/methodsWe conducted a large prospective family cohort study in 640 subjects (of whom 341 carriers and 299 non-carriers) belonging to 86 families with inherited deficiency of AT, PC, or PS.ResultsA total of 4240 and 3810 patient-years were available for carriers and non-carriers, respectively. Risk factors for atherosclerosis were similarly distributed in the two groups. Of the 26 ATE that were recorded, 19 occurred in carriers (5.6%), as compared to 7 in non-carriers (2.3%) [p = 0.07]. After adjusting for confounders, the hazard ratio (HR) for ATE was 4.9 (95% CI 1.5–16.3) in carriers as compared to non-carriers.ConclusionsAmong family members of probands with an inherited deficiency of natural anticoagulants, carriers exhibit a risk of ATE that is almost five times higher than in non-carriers.

Association of tumor mutations with arterial thromboembolism risk in patients with solid cancer.

e13537 Background: Patients with cancer have an increased risk of arterial thromboembolic events (ATE). Clinical characteristics such as medical comorbidities, cancer type, cancer stage and a history of smoking are established risk factors for ATE, but scant data exist about the effect of cancer-specific genomic alterations. We aimed to determine whether individual tumor mutations influence ATE risk. Methods: We performed a retrospective cohort study using tumor mutational data from adults with solid cancers who had MSK-IMPACT testing at Memorial Sloan Kettering Cancer Center between 2014 and 2016. MSK-IMPACT is an FDA-authorized DNA sequencing panel targeting 341+ oncogenes and tumor suppressor genes identifying mutations, copy number alterations, and gene fusions in solid malignancies. The primary ATE outcome was defined as ischemic stroke, myocardial infarction or coronary revascularization and detected by systematic electronic health record assessments. Patients were followed up to one year from the date of tissue-matched blood control sampling to the first ATE or death. We used Cox proportional hazards regression adjusting for age, cancer type, cytotoxic chemotherapy treatment (time-dependent) and tobacco use to determine hazard ratios (HR) of individual genes for ATE risk. We adjusted for multiple comparisons using the Benjamini-Hochberg method. Results: Among 11,317 patients, mean age was 59 years (SD = 14 years) and 55% were women. The most frequent cancers were lung (16%), breast (15%), and colorectal (10%), and 73% were metastatic. During a median follow-up of 253 days, 151 patients had an ATE (1.3%). In multivariable analysis, genomic alterations in KRAS (HR, 2.11; CI, 1.41-3.16), STK11 (HR, 2.62; 95% CI, 1.49-4.59), and ROS1 (HR, 5.3; 95% CI, 1.93-14.58) were independently associated with an increased risk of ATE. Presence of clonal hematopoiesis was not found to be associated with an increased risk of ATE in this cohort (HR, 0.96; 95% CI, 0.63-1.47). Conclusions: In a large genomic tumor-profiling registry of patients with solid cancers, alterations in KRAS, STK11, and ROS1 were associated with an increased risk of ATE independent of cancer type. [Table: see text]

Effect of intravitreal injection of aflibercept on blood coagulation parameters in patients with age-related macular degeneration.

Purpose:Treatment with intravitreal injections of anti-vascular endothelial growth factor agents has been associated with an increased risk of arterial thromboembolic events. The aim of the present pilot study was to assess the effect of a single intravitreal injection of aflibercept on coagulation.Methods:Treatment-naïve patients with age-related macular degeneration (n = 47), who were scheduled to undergo treatment with intravitreal injections of aflibercept, were enrolled. None of the included patients received any anticoagulation therapy or had a history of a recent arterial thromboembolic event. Blood samples were collected before the first intravitreal injection, and at 7 and 30 days after aflibercept administration. We evaluated coagulation parameters, such as platelet count and plasma fibrinogen and D-dimer levels; functional clotting parameters, such as prothrombin time, international normalized ratio, and activated partial thromboplastin time; and anticoagulant parameters, such as the levels of Proteins S and C.Results:The levels of all of the evaluated biomarkers were within the normal range at baseline and at both the time points throughout the study. No statistically significant changes were observed in any of the measured parameters at 1 week and 1 month after aflibercept administration.Conclusion:A single intravitreal injection of aflibercept in treatment-naïve patients with exudative age-related macular degeneration has no statistically significant effect on blood coagulation parameters for up to 1 month after aflibercept administration. Our results also provide an explorative statistical data, and further studies are required to evaluate any significant clinical effects of aflibercept on blood coagulation parameters.ClinicalTrials.gov ID:NCT03509623.

The risk of arterial thromboembolic events after cancer diagnosis

BackgroundRetrospective studies have reported an association between cancer and arterial thromboembolic event (ATE) risk. ObjectivesWe sought to confirm this in a prospective cohort with adjudicated outcomes. MethodsWe evaluated participants enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study with Medicare coverage for 365 days before their baseline visit (2003‐2007). Medicare claims were used to identify new cancer diagnoses during follow‐up. Using incidence‐density sampling, participants who developed cancer were matched by age, sex, race, and education 1:4 to control participants who had not developed cancer. Participants were prospectively followed through 2015 for an expert‐adjudicated ATE, defined as acute myocardial infarction or ischemic stroke. Cox regression was performed to evaluate the association between incident cancer and subsequent ATE. ResultsIn this analysis, 836 REGARDS participants with incident cancer were matched to 3339 control participants without cancer. In the 30 days after cancer diagnosis, 0.60% (n = 5) of the participants had an ATE; most of these events occurred near the time of cancer diagnosis. After adjustment for demographics, geographic region, and cardiovascular risk factors, compared to the noncancer controls, participants with incident cancer had an increased risk of ATE in the first 30 days after diagnosis (hazard ratio, 5.8; 95% confidence interval, 2.1‐15.9). There was no association between cancer diagnosis and ATE beyond 30 days. Cancers with known metastases and types considered high risk for venous thromboembolism had the strongest associations with ATE. ConclusionsIncident cancer is associated with an increased short‐term risk of ATE independent of vascular risk factors.

Risk of arterial thromboembolic events (ATEs) with tyrosine kinase inhibitors (TKIs) used in renal cell carcinoma: A systematic review and meta-analysis.

e13119 Background: Tyrosine kinase inhibitors (TKIs) are routinely used in the treatment of metastatic RCC and Sunitinib is approved for the use in adjuvant setting. Arterial thromboembolic events (ATEs) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence associated with the use of FDA approved TKIs used in treatment of RCC. Methods: PubMed, EMBASE, Cochrane Central and Scopus databases were searched to identify phase 2 and 3 RCTs of TKI therapy in RCC. Trials were included if they reported ATEs defined as arterial thrombosis, cerebral ischemia or infarction, myocardial ischemia and myocardial infarction. The DerSimonian-Laird random effects meta-analysis was performed using CMAv3 software to derive pooled estimates of incidence rates of ATEs with its 95% confidence interval (CI). I2 statistic was computed to express the percentage of the total observed variability due to study heterogeneity. Risk for bias was assessed using the Cochrane Collaboration’s tool. Results: 1755 studies retrieved in the initial search, and 13 phase 2 and 3 clinical trials (n = 4983) were included in the quantitative analysis. The trials had open label design which can potentially result in bias. Risk of bias was low in all other domains. TKIs used for the treatment of RCC included sunitinib (n = 2632), sorafenib (n = 981), cabozantinib (n = 78), pazopanib (n = 844), axitinib (n = 189) and tivozanib (n = 259). The incidence of ATEs with the use of TKIs was 2.9% (95% CI: 2-3%). Cabozantinib was associated with the highest rate of ATEs (11.5%, 95% CI: 6-21%), followed by sunitinib (2.6%, 95% CI:2-3%) pazopanib (2.6%, 95% CI:2-4%) and axitinib (2.1%, 95% CI: 1-6%). The TKI with lowest event rate of ATE was tivozanib (0.8%, 95% CI:0.2-3%). Conclusions: The use of TKIs is associated with increased risk of developing ATEs. Clinicians should be aware of the possibility of increased ATEs and counsel the patients about this increased risk to enhance the process of informed decision making.

Arterial thromboembolic events preceding the diagnosis of cancer in older persons

AbstractCancer patients face an increased risk of arterial thromboembolism; however, it is uncertain when this excess risk begins. This study evaluated the risk of arterial thromboembolism before cancer diagnosis. Using the population-based Surveillance Epidemiology and End Results-Medicare linked dataset, we identified 374 331 patients ≥67 years of age with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, uterine, pancreatic, gastric cancer, or non-Hodgkin lymphoma from 2005 through 2013. Cancer patients were individually matched by demographics and comorbidities to Medicare beneficiaries without cancer, who served as controls. Validated diagnosis codes were used to identify arterial thromboembolic events, defined as a composite of myocardial infarction or ischemic stroke. The Mantel-Haenszel estimator was used to compare risks of arterial thromboembolic events between cancer and noncancer groups during 30-day periods in the 360 days before date of cancer diagnosis. From 360 to 151 days before cancer diagnosis, the 30-day interval risks of arterial thromboembolic events were similar between cancer patients and matched controls. From 150 to 1 day before cancer diagnosis, the interval 30-day risks of arterial thromboembolic events were higher in cancer patients vs matched controls, progressively increasing as the cancer diagnosis date approached and peaking during the 30 days immediately before cancer diagnosis, when 2313 (0.62%) cancer patients were diagnosed with an arterial thromboembolic event vs 413 (0.11%) controls (odds ratio, 5.63; 95% confidence interval, 5.07-6.25). In conclusion, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis in older persons and peaks in the 30 days before.

Abstract WMP53: New Diagnosis of Cancer and the Risk of Subsequent Arterial Thromboembolic Events

Background: Retrospective studies have reported an association between cancer and arterial thromboembolism risk. We sought to confirm this in a prospective cohort with adjudicated cardiovascular outcomes. Methods: We analyzed data from participants enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study who had Medicare coverage for 365 days before their baseline study visit in 2003-2007. Participants with prevalent cancer, coronary heart disease, or cerebrovascular disease were excluded. Medicare claims were used to identify new cancer diagnoses during follow-up. Using incidence-density sampling, participants who developed cancer were matched by age, sex, race, and education level 1:4 to participants who hadn’t developed cancer. Participants were prospectively followed through September 30, 2015 for an adjudicated arterial thromboembolic event, defined as fatal or nonfatal acute myocardial infarction or ischemic stroke. Cox regression was performed to evaluate the association between incident cancer and subsequent arterial thromboembolic events. To fulfill the proportional hazard assumption, follow-up time was modeled in discrete time periods. Results: In this analysis, 836 REGARDS participants with incident cancer were matched to 3,339 participants without cancer. During median follow-up of 3 years, 63 (7.5%) participants with cancer and 216 (6.5%) participants without cancer had an arterial thromboembolic event. Compared to non-cancer controls, participants with incident cancer had an increased risk of arterial thromboembolic events in the first 30 days after diagnosis (HR, 5.2; 95% CI, 2.1-12.7). This association persisted after adjustment for demographics, region of residence, and cardiovascular risk factors (HR, 5.8; 95% CI, 2.1-15.9). Cancers with known metastases and types considered high-risk for venous thromboembolism had the strongest associations with arterial thromboembolic events. There was no association between cancer diagnosis and arterial thromboembolic event risk beyond 30 days. Conclusions: Incident cancer, particularly when metastatic, is associated with an increased short-term risk of arterial thromboembolic events independent of vascular risk factors.

Continued vs. interrupted direct oral anticoagulants at the time of device surgery, in patients with moderate to high risk of arterial thrombo-embolic events (BRUISE CONTROL-2).

Guidelines recommend warfarin continuation rather than heparin bridging for pacemaker and defibrillator surgery, after the BRUISE CONTROL trial demonstrated an 80% reduction in device pocket haematoma with this approach. However, direct oral anticoagulants (DOACs) are now used to treat the majority of patients with atrial fibrillation. We sought to understand the best strategy to manage the DOACs at the time of device surgery and specifically hypothesized that performing device surgery without DOAC interruption would result in a reduced haematoma rate. We randomly assigned patients with atrial fibrillation and CHA2DS2-VASc score ≥2, to continued vs. interrupted DOAC (dabigatran, rivaroxaban, or apixaban). The primary outcome was blindly evaluated, clinically significant device pocket haematoma: resulting in re-operation, interruption of anticoagulation, or prolonging hospital stay. In the continued arm, the median time between pre- and post-operative DOAC doses was 12 h; in the interrupted arm the median time was 72 h. Clinically significant haematoma occurred in of 7 of 328 (2.1%; 95% CI 0.9-4.3) patients in the continued DOAC arm and 7 of 334 (2.1%; 95% CI 0.9-4.3) patients in the interrupted DOAC arm (P = 0.97). Complications were uncommon, and included one stroke and one symptomatic pericardial effusion in each arm. These results suggest that, dependent on the clinical scenario, either management strategy (continued DOAC or interrupted DOAC) might be reasonable, at least for patients similar to those enrolled in our trial.

Pegaptanib: choroidal neovascularization in patients with age-related macular degeneration and previous arterial thromboembolic events.

To evaluate the efficacy and the rate of side effects of the pegylated aptamer pegaptanib in the treatment of patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and a history of previous arterial thromboembolic events (ATEs). Twenty-three eyes of 23 patients with subfoveal CNV due to AMD and cerebrovascular accidents (n = 12) and myocardial infarction (n = 11) in the previous 6 months received intravitreal pegaptanib 0.3 mg according to a pro re nata regimen and were followed for 12 months. The paired Student t test was used to evaluate mean changes in best-corrected visual acuity (BCVA; primary outcome measure) and central foveal thickness (CFT). The mean patient age was 71.5 ± 4.6 years; there were 14 women and 9 men. The CNV was type 1, 2, and 3 in 18, 3, and 2 eyes, respectively. The mean BCVA improved from 0.67 ± 0.23 logMAR at baseline to 0.52 ± 0.31 logMAR at the end of 12-month follow-up (p = 0.044). Thirty-five percent of patients achieved ≥3 Early Treatment Diabetic Retinopathy Study lines improvement at 12 months. Mean CFT at baseline (381 ± 111 µm) decreased to 304 ± 82 µm at 12 months (p = 0.008). Patients received a mean of 4.3 ± 1.3 (range 3-7) injections. No systemic or ocular side effects occurred; no patient experienced further ATEs. Intravitreal pegaptanib can be considered a viable treatment option for patients with AMD-related CNV who are at high risk of ATEs.

Increased risk of arterial thromboembolism in older men with breast cancer.

Male breast cancer is a rare and understudied disease predominantly affecting men over age 60. Risk of arterial thromboembolic events (ATE) in men increases with age. We examined ATE risk following primary breast cancer diagnosis in elderly men. Men with primary breast cancer diagnoses from 2002 to 2011 were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Cases were individually matched by age, sex, race, registry, and comorbidities with controls without cancer using SEER-Medicare's 5% noncancer sample. Medicare claims were used to identify ATE, defined as myocardial infarction or ischemic stroke. Cumulative incidence of ATE was calculated using competing risk methodology, with death considered a competing event. Cox proportional hazards analysis was used to compare rates of ATE among cases and controls. Three months following primary breast cancer diagnosis, ATE risk in the cohort of 881 men was 80% higher than matched controls (hazard ratio 1.8; 95% confidence interval 1.0-3.2). Sixmonths post-cancer diagnosis, 5.7% of cases had experienced ATE, whereas only 3.5% of controls had (HR 1.6; 95% CI 1.0-2.6). ATE risk remained elevated 12months post-cancer diagnosis. Among cases, risk of death was threefold higher in men who developed ATE. We provide population-based evidence that male breast cancer patients have a substantially elevated risk of ATE in the first year following a cancer diagnosis compared with matched controls. Care providers should consider this heightened risk when evaluating cardiovascular health in men with a recent breast cancer diagnosis.