Incidence Of Arterial Thromboembolic Events Research Articles

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.

Study of thrombotic complications in COVID-19

Background: In December of 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began to infect humans in the city of Wuhan and has rapidly become pandemic. Recent clinical trials suggested that COVID-19 related thromboembolic complications are the major cause for increased incidence of morbidity and mortality. We conducted a prospective observational study to evaluate the prevalence of vascular complications due to COVID-19 and to analyse the difference in the inflammatory markers before and after the events.Methods: Prospective observational study, conducted at department of general medicine, Bangalore Medical College, Bangalore Karnataka from 3 months, 01 August 2021 to 30 October 2020. The incidence of thrombotic events was 70.7% (53/75). The incidence of arterial thromboembolic events was 48%, involving 36 patients of the overall study population. Of these 36 patients, majority of them were suffering from cerebrovascular accident (CVA) accounting for about 12 (16%) of the patients followed by 11 (14.7%) with ischemic heart disease (IHD). About 22.66% (17/75) of patients had developed venous thromboembolic events. Of which, 13 (17.3%) patients had developed deep-vein thrombosis (DVT).Results: We observed that all the inflammatory markers had significantly increased after the onset of thrombotic events. Serum ferritin, lactate dehydrogenase (LDH), interleukin-6 (IL-6) and fibrinogen were almost raised by 50% of the pre-event values. We could not calculate the sensitivity, specificity, positive predictive value and negative predictive value for each parameter as the severity of the disease was widely distributed. Majority of these thrombotic events were observed among the patients aged >60 years and those with comorbid conditions. But there no statistically significant difference observed.Conclusions: We concluded that COVID-19 causes significantly increased surge of inflammatory markers and thereby the significantly increased prevalence of arterial and venous thrombotic events.

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.

The role of prophylactic use of low molecular weight heparin or aspirin in thromboembolic events in primary membranous nephropathy

Objective: The aim of this study is to investigate the role of prophylactic anticoagulation regimens based on low molecular weight heparin (LMWH) or aspirin in thromboembolic events in patients with primary membranous nephropathy (PMN).Methods: A total of 717 patients with PMN were consecutively enrolled in this retrospective study. The propensity score matching method was utilized to adjust for the selection bias inherent in an analysis of outcomes, which was stratified by the anticoagulation prophylaxis regimen.Results: According to the anticoagulation prophylaxis regimen, patients were assigned into three groups: only LMWH therapy (L + A−, n = 53), only aspirin therapy (L − A+, n = 97), and no therapy of LMWH or aspirin (L − A−, n = 567). After performing 1:1 match, 37 patients were selected in the L + A − group and the L − A− group, respectively, and 94 patients were selected in the L − A+ group and the L − A− group, respectively. It showed that the prophylactic use of LMWH had no protective effects on arterial thromboembolic events (ATEs) (10.8% vs. 21.6%, p = .21) or venous thromboembolic events (VTEs) (8.1% vs. 10.8%, p = .69). The incidence of VTEs in the L − A+ group was lower than the L − A− group (2.1% vs. 10.6%, p = .02), while there were no significant differences in the incidences of ATEs between the L − A+ group and the L − A− group (5.3% vs. 7.4%, p = .55).Conclusions: The prophylactic use of LMWH showed no benefits on the incidence of ATEs or VTEs in patients with PMN. Aspirin effectively decreased the incidence of VTEs, without effects on the occurrence of ATEs.

Arterial Thrombosis in Patients with Cancer.

Cancer is a common cause of morbidity and mortality in the USA. While the association between venous thrombosis and malignancy is well established, arterial thrombosis has more recently been recognized as a serious complication of cancer and certain chemotherapeutic agents. This review aims to summarize the most recent literature regarding the incidence and risk factors for cancer-related arterial thrombosis, understand the pathophysiologic mechanisms of thrombosis, and highlight the specific diagnostic and treatment considerations relevant to cancer patients. Based on a recent study looking at the Surveillance, Epidemiology, and End Results (SEER) database, the incidence of arterial thromboembolic events (ATEs) in patients with cancer at 6months is 4.7%; the presence of an ATE is predictive of worse outcomes. Certain drugs such as platinum-based agents, vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors, and taxanes have been associated with high rates of ATEs. Increased platelet reactivity appears crucial to development of arterial thrombosis in cancer patients. Cancer patients have an increased risk of arterial thrombosis that is likely due to both a cancer-associated procoagulant state as well as the adverse effects of certain chemotherapeutic agents. Treatment of arterial thromboembolism in cancer patients typically requires a multidisciplinary approach in part due to high rates of thrombocytopenia and stent thrombosis in the setting of percutaneous interventions. More studies are needed to investigate optimal prophylaxis, surveillance strategies, and treatments of cancer-related arterial thromboembolic disease.

Increased risk of arterial thromboembolic events with combination lenalidomide/dexamethasone therapy for multiple myeloma

ABSTRACTIntroduction: Cancer associated thrombosis is a leading cause of morbidity and mortality. Research and guidelines have focused on venous thromboembolic events (VTE). Within the past decade, combination lenalidomide and dexamethasone has become a standard of therapy for multiple myeloma and is now widely used. In these patients, the risk of arterial thromboembolic events (ATE) has not been addressed to the same extent as VTE.Areas discussed: Presented is a targeted review of published data on ATE in MM patients on combination lenalidomide/dexamethasone therapy. Incidence, clinical presentations, prognosis, mechanisms and thromboprophylaxis are discussed. A framework for approaching ATE/VTE in these patients is suggested.Expert commentary: There is an increased incidence of ATE in this population, primarily cerebrovascular and cardiovascular events. ATE is associated with poorer prognosis and its prevention must be an important goal of management. It is suggested that on initiating treatment, a combined VTE/ATE risk assessment should be performed and thromboprophylaxis initiated for a minimum of 6 months. As newer immunomodulatory therapies are developed, thromboembolic risk must be assessed early on. Further studies are needed to determine the optimal strategy to reducing both VTE and ATE in this population.

Antiplatelet versus oral anticoagulant therapy as antithrombotic prophylaxis after mitral valve repair

ObjectiveTo verify the rate of thromboembolic and hemorrhagic complications during the first 6 months after mitral valve repair and to assess whether the type of antithrombotic therapy influenced clinical outcome. MethodsRetrospective data were retrieved from 19 centers. Inclusion criteria were isolated mitral valve repair with ring implantation. Exclusion criteria were ongoing or past atrial fibrillation and any combined intraoperative surgical procedures. The study cohort consisted of 1882 patients (aged 58 ± 15 years; 36% women), and included 1517 treated with an oral anticoagulant (VKA group) and 365 with antiplatelet drugs (APLT group). Primary efficacy outcome was the incidence of arterial thromboembolic events within 6 months and primary safety outcome was the incidence of major bleeding within 6 months. Propensity matching was performed to obtain 2 comparable cohorts (858 vs 286). ResultsNo differences were detected for arterial embolic complications in matched cohort (1.6% VKA vs 2.1% APLT; P = .50). Conversely, patients in the APLT group showed lower incidence of major bleeding complications (3.9% vs 0.7%; P = .01). Six-month mortality rate was significantly higher in the VKA group (2.7% vs 0.3%; P = .02). Multivariable analysis in the matched cohort found VKA as independent predictor of major bleeding complications and mortality at 6 months. ConclusionsVitamin K antagonist therapy was not superior to antiplatelet therapy to prevent thromboembolic complications after mitral valve repair. Our data suggest that oral anticoagulation may carry a higher bleeding risk compared with antiplatelet therapy, although these results should be confirmed in an adequately powered randomized controlled trial.

Aflibercept for the treatment of age-related macular degeneration.

Aflibercept is a novel, recombinant, fusion protein that consists of portions of vascular endothelial growth factor (VEGF) receptor (R) 1 and VEGFR2 extracellular domains fused to the Fc portion of human immunoglobulin G1. It exhibits higher affinity for VEGF-A/-B and binds all the VEGF isoforms (VEGF-B and -C, placental growth factor). The efficacy of aflibercept was assessed in two randomized, double-masked, multicenter, active-controlled, clinical trials in patients with choroidal neovascularization due to exudative age-related macular degeneration (AMD) and compared it’s efficacy to ranibizumab, which is already Food and Drug Administration (FDA)-approved for patients with wet AMD. In the two trials known as VIEW 1 and VIEW 2, aflibercept was as effective when dosed as 2 mg every 8 weeks after 3 monthly loading doses compared to monthly ranibizumab. Aflibercept was well tolerated with very rare systemic adverse events, including arterial thromboembolic events (ATEs). The incidence of ATEs was 1.8% during the first year of the clinical trials and included non-fatal strokes, non-fatal myocardial infarction, or death from vascular events or an unknown cause. In November 2011, aflibercept received FDA approval and is currently used in clinical practice for patients with wet AMD.

Aflibercept: Bimonthly intravitreal injection for AMD

Aflibercept: Bimonthly intravitreal injection for AMD

Arterial Thromboembolic Events in Patients with Exudative Age-Related Macular Degeneration Treated with Intravitreal Bevacizumab or Ranibizumab

Background/Aims: To compare retrospectively the incidence of arterial thromboembolic events (ATEs) in patients treated with bevacizumab or ranibizumab for exudative age-related macular degeneration. Methods: Charts of 378 patients treated with at least 1 intravitreal injection of ranibizumab or bevacizumab were reviewed to calculate the incidence of ATEs. Only patients under monotherapy were analyzed. Results: ATEs occurred in 15 patients: 12 (12/97) with bevacizumab (12.4%) and 3 (3/219) with ranibizumab (1.4%) – odds ratio 10.16; 95% confidence interval 2.80–36.93; p < 0.0001. ATEs in the bevacizumab and ranibizumab cohorts included stroke, myocardial infarction, angina pectoris, peripheral thromboembolic disease, transient ischemic attack, sudden death and lethal stroke. Conclusion: In this series, bevacizumab raised the risk of ATEs when compared to ranibizumab. In an elderly population with multiple cardiovascular risk factors, the new ATEs may not be attributed exclusively to the intravitreal bevacizumab administration. These findings raise an issue that must be confirmed in randomized clinical trials.

Aortobifemoral embolism in an 18-year old patient following cisplatin and 5-fluorouracil chemotherapy for nasopharyngeal carcinoma

After cisplatin / 5-fluorouracil chemotherapy for nasopharyngeal carcinoma, an 18-year female patient developed aortobifemoral embolism. Besides chemotherapy, additional risk factors for arterial thromboembolic events were smoking, contraceptive medication and adjuvant antiemetic treatment with dexamethasone. Thrombophilia screening was negative. Thromboembolic complications during or after cisplatin have been reported in a frequency of 17.6 % in lung cancer patients, and in 8.4 % of patients with germ cell tumors. The incidence of arterial thromboembolic events was 9.3 % and 1.7 %, respectively. The pathogenesis of cisplatin induced thromboembolism is thought to be caused by endothelial damage leading to endothelial cell dysfunction, increased von Willebrand factor plasma levels, and hypomagnesaemia.

Breast Cancer Patients Are 30% More Likely To Develop Arterial Thromboembolic Events after Diagnosis Compared with Cancer-Free Women: Results from a Large Population-Based Study.

Abstract Background: Population-based prevalence and incidence data of arterial thromboembolic events (ATEE) in breast cancer (BC) patients are lacking in the published literature.Objectives: The occurrence of ATEE before and after BC diagnosis was compared with cancer-free controls in a population-based setting.Methods: Women who had a first hospitalization for BC between 2002 and 2007 were selected from the PHARMO Record Linkage System (RLS), which includes drug use and hospitalization data from approximately 3 million residents in the Netherlands. BC patients were matched 1:10 by age with cancer-free controls, using the date of diagnosis as the index date for both BC patients and controls. ATEE were defined as a myocardial infarction, unstable angina, ischemic stroke, and transient ischemic attack requiring hospitalization and were assessed 12 mo before and after the index date.Results: The analysis included 11,437 BC patients, with a mean ± SD age of 59 ± 14 years. ATEE before the index date were twice as frequent among BC patients compared with cancer-free controls (Table 1), though prevalence was &amp;lt; 1% in both groups. The incidence of developing ATEE in the 12-mo follow-up period was 6.2 per 1000 person years among patients and 3.8 among controls (Table 2). BC patients experienced 1.7 times higher risk of ATEE compared with controls. This risk was attenuated but remained statistically significant after adjusting for prior cardiovascular or thromboembolic event hospitalization and prior antithrombotic or cardiovascular drug use (HR=1.3 [95%CI: 1.0-1.7]). The increase in risk was slightly higher for cerebrovascular compared with coronary events. Independent risk factors for developing ATEE were age (≥ 65 vs &amp;lt; 65 years), prior use of antihypertensives or antidiabetic drugs, and total hospital stay &amp;gt; 10 days during the first 6 months of follow-up.Table 1. Prevalence of ATEE 12 mo Before BC Diagnosis BC Patients (N=11,473) %Cancer-free Patients (N=114,730) %Odds Ratio (95% CI)ATEE0.70.32.0 (1.6-2.6)Myocardial Infarction0.30.12.9 (1.9-4.2)Unstable Angina0.20.11.5 (0.9-2.3)Ischemic Stroke0.10.11.8 (1.0-3.1)Transcient Ischemic Attack0.10.02.1 (1.2-4.0) Table 2. Incidence of ATEE 12 mo After BC Diagnosis BC Patients (N=11,473) IR per 1000 PYCancer-free Controls (N=114,730) IR per 1000 PYHazard Ratio (95% CI)ATEE6.23.81.7 (1.3-2.2)Myocardial Infarction1.71.31.4 (0.8-2.2)Unstable Angina1.61.21.4 (0.8-2.2)Ischemic Stroke1.60.82.0 (1.2-3.3)Transcient Ischemic Attack1.40.82.5 (1.4-4.3) Conclusions: In this large population-based study, the occurrence of the arterial thromboembolic events was low. However, BC patients were at significantly higher risk of developing ATEE compared with cancer-free controls. These results emphasize the need for careful observation of BC patients after diagnosis. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2050.