Vascular Thromboembolic Events Research Articles

Abstract 17381: Relationship Between Amaurosis Fugax and Intraplaque Hemorrhage in Patient With Carotid Plaques

Introduction: The term amaurosis fugax is often used interchangeably to describe transient visual loss. However, it is employed widely in medicine to refer to any cause of transient monocular visual loss. Amaurosis fugax is associated with an imminent stroke and it could be linked to vascular thromboembolic events arising from the internal carotid arterial system. The aims of the study are to determine the plaque characteristics of patients who underwent carotid artery revascularization and the relationship of plaque characteristics with amaurosis fugax. Methods: Before elective carotid revascularization 44 patients (mean age 72±8 years; 25 males, 19 females) underwent 3-T MRI. After localization of the carotid bifurcation using phase contrast imaging, Time-of-Flight, 3D T1 weighting, transverse T1 and T2 weightings and proton density sequences were acquired. The different plaque components: lipid rich core, intraplaque hemorrhage, calcification and the characterization of the fibrous cap were assessed. Results: Carotid plaque samples had the following characteristics: Intraplaque hemorrhage (59%), surface defects (38.6%), stable fibrous cap (27.3%), lipid rich necrotic core (18%), and calcifications (11.4%). Amaurosis fugax history was identified in 7 patients (15.9%). Plaque samples from all 7 patients who had experienced amaurosis fugax revealed intraplaque hemorrhage. MRI revealed intraplaque hemorrhage in 19 (51%) patients without history of amaurosis fugax (p=0.016). The rest of the plaque characteristics did not show any statistically significant relationship with history of amaurosis fugax. Conclusions: This study demonstrated that intraplaque hemorrhage may be correlated to amaurosis fugax.

Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis.

To evaluate the relationship between testosterone replacement therapy (TRT) and arterial and/or venous thrombosis in patients with pre-treatment total testosterone (TT) <12 nmol l -1 , we performed a meta-analysis following the Population Intervention Comparison Outcome model. Population: men with TT <12 nmol l -1 or clear mention of hypogonadism in the inclusion criteria of patients; intervention: TRT; comparison: placebo or no therapy; outcomes: arterial thrombotic events (stroke, myocardial infarction [MI], upper limbs, and lower limbs), VTE (deep vein thrombosis [DVT], portal vein thrombosis, splenic thrombosis, and pulmonary embolism), and mortality. A total of 2423 abstracts were assessed for eligibility. Twenty-four studies, including 14 randomized controlled trials (RCTs), were finally included, with a total of 4027 and 310 288 hypotestosteronemic male patients, from RCTs and from observational studies, respectively. Based on RCT-derived data, TRT did not influence the risk of arterial thrombosis (odds ratio [OR] = 1.27, 95% confidence interval [CI]: 0.47-3.43, P = 0.64), stroke (OR = 1.34, 95% CI: 0.09-18.97, P = 0.83), MI (OR = 0.51, 95% CI: 0.11-2.31, P = 0.39), VTE (OR = 1.42, 95% CI: 0.22-9.03, P = 0.71), pulmonary embolism (OR = 1.38, 95% CI: 0.27-7.04, P = 0.70), and mortality (OR = 0.70, 95% CI: 0.20-2.38, P = 0.56). Meanwhile, when only observational studies are considered, a significant reduction in the risk of developing arterial thrombotic events, MI, venous thromboembolism, and mortality was observed. The risk for DVT remains uncertain, due to the paucity of RCT-based data. TRT in men with TT <12 nmol l -1 is safe from the risk of adverse cardiovascular events. Further studies specifically assessing the risk of DVT in men on TRT are needed.

Managing surgery in hemophilia with recombinant factor VIII Fc and factor IX Fc: Data on safety and effectiveness from phase 3 pivotal studies

BackgroundSurgical procedures impose hemostatic risk to people with hemophilia, which may be minimized by optimal factor (F) replacement therapy. MethodsThis analysis evaluates the efficacy and safety of extended half‐life factor replacement recombinant FVIII and FIX Fc fusion proteins (rFVIIIFc and rFIXFc) during surgery in phase 3 pivotal (A‐LONG/Kids A‐LONG and B‐LONG/Kids B‐LONG) and extension (ASPIRE and B‐YOND) studies. Dosing regimens were determined by investigators. Injection frequency, dosing, blood loss, transfusions, and hemostatic response were assessed. ResultsForty‐five major (n = 31 subjects) and 90 minor (n = 70 subjects) procedures were performed in hemophilia A; 35 major (n = 22) and 62 minor (n = 37) procedures were performed in hemophilia B. Unilateral knee arthroplasty was the most common major orthopedic procedure (hemophilia A: n = 15/34; hemophilia B: n = 8/24). On the day of surgery, median total dose in adults/adolescents was 81 IU/kg for rFVIIIFc and 144 IU/kg for rFIXFc; most major procedures required ≤2 injections (including loading dose). Through days 1–14, most major procedures had ≤1 injection/day. Hemostasis was rated excellent (rFVIIIFc: n = 39/42; rFIXFc: n = 29/33) or good (n = 3/42; n = 4/33) in evaluable major surgeries, with blood loss comparable with subjects without hemophilia. Most minor procedures in adults/adolescents required one injection on the day of surgery, including median loading dose of 51 IU/kg (rFVIIIFc) and 80 IU/kg (rFIXFc). No major treatment‐related safety concerns were identified. No subjects developed inhibitors or serious vascular thromboembolic events. ConclusionsrFVIIIFc and rFIXFc were efficacious and well tolerated for the management of perioperative hemostasis across a wide spectrum of major and minor surgeries in hemophilia.

Incidence of Vascular Thromboembolic Events in Patients Receiving Immunotherapy: A Single Institution Experience

Introduction:Cancer is known to cause a hypercoagulable state predisposing to venous thromboembolism (VTE). In a retrospective study by Lyman et al., the incidence of VTE 3.5 months after starting chemotherapy was 7.3% rising to 13.5% at 12 months in a cohort of more than 27,000 patients. A two-fold increase in the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) has also been reported in hospitalized cancer patients compared to non-cancer patients. Systemic cancer treatments are known to be associated with increased VTE risk but the incidence of vascular thromboembolic events with newer treatment modalities like immunotherapy has not been broadly investigated. This study aims to assess the incidence of vascular events including VTE, strokes and myocardial infarction in cancer patients receiving anti PD1/PDL1 therapy at a single institution.Methods:We retrospectively analyzed the data of 154 cancer patients over 18 years of ages, who were treated with anti PD-1/PDL-1 therapy at the University of Oklahoma from 2014 to 2016. We used descriptive statistics to describe the incidence of vascular thromboembolic events. Kaplan Meier Survival analysis was used to estimate the progression free survival (PFS) according to VTE occurrence.Results:The majority of patients were females (57%). The median age was 63 years (range 23-89). Median number of treatments received was 5 (range 1-30). Lung cancer was the most common diagnosis (20.8%) followed by melanoma (20.1%) and ovarian cancer (12.3%). 92% of patients had stage 4 cancer. Nivolumab was the most commonly used agent (47.4%) followed by Pembrolizumab (22.7%), other investigational agents (22.7%) and Atezolizumab (7.2%).The median follow up time was 198 days (approximately 7 months). VTE occurred in 16/154 patients (10%). Nine patients had DVT, 6 patients had PE and 1 patient had DVT and PE. VTE was most common in patients with lung cancer (17%) and patients with ovarian cancer (17%). The occurrence of VTE was not significantly associated with a worse progression free survival [150 days versus 146 days for VTE occurrence vs no occurrence respectively (p = 0.725)]. No cases of stroke or myocardial infarction were recorded.Conclusion:The incidence of VTE in this cohort of cancer patients receiving immunotherapy appeared to be similar to the incidence previously reported with other systemic therapies. No arterial thromboembolic events were recorded in our study. Large multicenter studies are needed to derive definite conclusions. DisclosuresNo relevant conflicts of interest to declare.

Vascular thromboembolic events following COVID‐19 hospital discharge: Incidence and risk factors

BackgroundCoronavirus disease 2019 (COVID‐19) is associated with high rates of thromboembolic events in hospitalized patients. It remains to be determined if this risk persists following hospital discharge. MethodsWe conducted a retrospective cohort study of outpatients recently hospitalized for COVID‐19 to determine the incidence of vascular thromboembolic events within 30 days of discharge. We investigated the risk factors associated with these events, including intensive care admission, age, and anticoagulation. ResultsAmong 447 patients hospitalized for COVID‐19, 2.0% experienced a vascular thromboembolic event within 30 days of discharge. No risk factor variable was significantly associated with an increased risk for these events. ConclusionsThe incidence of vascular thromboembolic events following hospital discharge for COVID‐19 is low. These findings suggest against the routine use of postdischarge thromboprophylaxis in patients with COVID‐19.

Incidence of Vascular Thromboembolic Events in Outpatients with Mild COVID-19

IntroductionHypercoagulability is a hallmark of COVID-19, the disease caused by the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2).1 While studies have investigated vascular thromboembolic events (VaTE) in critically ill and hospitalized patients with COVID-19, less is known about thrombotic complications in patients with mild symptoms.2 Our current institutional management protocol recommends prophylactic anticoagulation for COVID-19 patients admitted to the hospital but not for outpatients with less severe disease. We evaluated the incidence of VaTE in outpatients diagnosed with COVID-19 at our institution in order to assess the potential need for thromboprophylaxis in outpatient COVID-19 management.MethodsWe conducted a retrospective analysis of electronic medical record data of outpatients in the University of North Carolina Health System who tested positive for Sars-CoV-2 between March 15 and June 20, 2020. Patients were diagnosed at one of 17 ambulatory respiratory diagnostic centers (n=706), or diagnosed and subsequently discharged from one of 11 emergency departments (n=1967) in the UNC system. Diagnosis was made using reverse transcriptase polymerase chain reaction testing of nasopharyngeal or oropharyngeal swab samples. The study outcome was the diagnosis of a vascular thromboembolic event within 30 days of COVID-19 diagnosis. This included deep vein thrombosis, pulmonary embolism, superficial thrombophlebitis, myocardial infarction, ischemic stroke, and systemic arterial thromboembolism. VaTE was defined based on documentation of an associated ICD-10 code in the patient's electronic medical record within the specified time frame. Outcomes data were reported as incidence rates for the entire study population.Results2673 outpatients were diagnosed with COVID-19 in the study period. The mean age for this cohort was 37.9 ± 17.3 years and 54% were female. 20 unique individuals (0.7%) experienced a VaTE within 30 days of diagnosis. Of these, 3 (15%) experienced venous thromboembolic events, 16 (80%) experienced arterial events, and 1 patient experienced both. Mean time to VaTE was 12.8 ± 9.3 days. Within 30 days of diagnosis, 188 of these patients (7%) had an emergency department visit or experienced hospital observation or inpatient admission.ConclusionsWe found that the incidence of VaTE in outpatients with mild COVID-19 is low. Limitations of this study include that patients were not routinely screened for VaTE and may have sought treatment for thrombotic complications outside the hospital system. This may have led to an underestimate of the true incidence; however, the findings are in line with data showing that non-hospitalized COVID-19 patients tend to be younger and have fewer medical comorbidities than hospitalized patients.3 This argues against the routine use of thromboprophylaxis in outpatients with COVID-19.

Deep vein thrombosis in hospitalized patients with coronavirus disease 2019

ObjectiveThe pandemic of coronavirus disease 2019 (COVID-19) has caused devastating morbidity and mortality worldwide. In particular, thromboembolic complications have emerged as a key threat for patients with COVID-19. We assessed our experience with deep vein thrombosis (DVT) in patients with COVID-19. MethodsWe performed a retrospective analysis of all patients with COVID-19 who had undergone upper or lower extremity venous duplex ultrasonography at an academic health system in New York City from March 3, 2020 to April 12, 2020 with follow-up through May 12, 2020. A cohort of hospitalized patients without COVID-19 (non–COVID-19) who had undergone venous duplex ultrasonography from December 1, 2019 to December 31, 2019 was used for comparison. The primary outcome was DVT. The secondary outcomes included pulmonary embolism, in-hospital mortality, admission to the intensive care unit, and antithrombotic therapy. Multivariable logistic regression was performed to identify the risk factors for DVT and mortality. ResultsOf 443 patients (COVID-19, n = 188; and non–COVID-19, n = 255) who had undergone venous duplex ultrasonography, the COVID-19 cohort had had a greater incidence of DVT (31% vs 19%; P = .005) than had the non–COVID-19 cohort. The incidence of pulmonary embolism was not significantly different statistically between the COVID-19 and non–COVID-19 cohorts (8% vs 4%; P = .105). The DVT location in the COVID-19 group was more often distal (63% vs 29%; P < .001) and bilateral (15% vs 4%; P < .001). The duplex ultrasound findings had a significant impact on the antithrombotic plan; 42 patients (72%) with COVID-19 in the DVT group had their therapy escalated and 49 (38%) and 3 (2%) had their therapy escalated and deescalated in the non-DVT group, respectively (P < .001). Within the COVID-19 cohort, the D-dimer level was significantly greater in the DVT group at admission (2746 ng/mL vs 1481 ng/mL; P = .004) and at the duplex examination (6068 ng/mL vs 3049 ng/mL; P < .01). On multivariable analysis, male sex (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.06-4.87; P = .035), intensive care unit admission (OR, 3.42; 95% CI, 1.02-11.44; P = .046), and extracorporeal membrane oxygenation (OR, 5.5; 95% CI, 1.01-30.13; P = .049) were independently associated with DVT. ConclusionsGiven the high incidence of venous thromboembolic events in this population, we support the decision to empirically initiate therapeutic anticoagulation for patients with a low bleeding risk and severe COVID-19 infection. Duplex ultrasonography should be reserved for patients with a high clinical suspicion of venous thromboembolism for whom anticoagulation therapy could result in life-threatening consequences. Further study of patients with COVID-19 is warranted to elucidate the etiology of vascular thromboembolic events and guide the prophylactic and therapeutic interventions for these patients.

Electrical weapons, hematocytes, and ischemic cardiovascular accidents

BackgroundThere have been case reports following the use of a conducted electrical weapon (CEW) suggesting that these devices might affect coagulation or thrombosis in at-risk individuals. The aim of this manuscript therefore is firstly to explore this hypothesis by reviewing each of these cases and secondly to report the results of a prospective study exploring a priori the effects of electrical weapons on hematocytes in a group of human volunteers. MethodsFirst, we systematically reviewed all cases of adverse outcomes following CEW discharge that could be due to an effect on coagulation or thrombosis, with particular focus on the clinical scenario and its relationship with the weapon discharge. Second, we assessed hematocyte levels in venous blood from 29 volunteers before, 5 min after, and 24 h after receiving a full-trunk 5-s TASER® X26(E) CEW exposure. ResultsFollowing extensive review of the literature, we found 3 relevant case reports of possible vascular thromboembolic clinical events after CEW exposure, specifically a case of ischemic stroke, and 2 cases of ST-segment elevation myocardial infarctions. Review of these published cases failed to establish a plausible linkage to the CEW beyond a temporal association with significant emotional and physiological stress from a violent struggle.Our prospective study of biomarker change following CEW discharge revealed acutely increased values for WBC (white blood cells), specifically lymphocytes and monocytes, and a raised platelet count. Neutrophil levels decreased as a percentage of WBC. While these changes were statistically significant at 5 min, all results remained within established reference ranges. At 24 h, all values had returned to baseline except total WBC which decreased to slightly below baseline but was still within the normal reference range. ConclusionsA review of clinical cases, of ischemic or thrombotic events revealed no direct association with the CEW discharge. A full-trunk electrical weapon exposure did not lead to hematocyte changes beyond normal clinically expected variations in similar acute response scenarios. The case report and biomarker data do not support the hypothesis that a CEW discharge is associated with changes likely to promote coagulation or thrombus formation.

1775P - Incidence of vascular thromboembolism events in cancer patients receiving immunotherapy: A single institution experience

BackgroundCancer and cancer therapy, such as chemotherapy and vascular endothelial growth factor targeted therapies, have been associated with an increased incidence of vascular thromboembolic events (VTEs): deep venous thrombosis (DVT), pulmonary embolus (PE), arterial thromboembolism (ATE), cerebrovascular accident (CVA), and myocardial infarction. However, the incidence of VTEs in patients on immunotherapy has not been well characterized. The purpose of this study was to assess the incidence of VTEs in cancer patients receiving immunotherapy in our institution. MethodsWe conducted a single institution retrospective cohort study, which included all cancer patients treated with anti PD-1/PD-L1 or anti CTLA-4 therapy from June 2013 to April 2019. Data regarding clinical characteristics, incidence of VTEs and survival were collected. ResultsWe selected 229 patients treated with immunotherapy, of whom the majority (n=146, 63.8%) were males with a median age of 64 years (range 19 to 86 years). Lung cancer was the most frequent tumor treated with immunotherapy (n=110, 48.0%) followed by melanoma (n=54, 23.6%) and renal cell carcinoma (RCC) (n=27, 11.8%). Pembrolizumab was the most commonly used single drug immunotherapy (n=92, 40.2%) and nivolumab plus ipilimumab was the most common multidrug regimen (n=17, 7.4%). VTEs occurred in 18 of 229 patients (7.9%). 6 patients had DVT, 7 patients had PE, 3 patients had DVT plus PE, 1 patient had ATE and 1 patient had CVA. 13 of 18 VTEs (72.2%) were symptomatic. VTEs occurred in 12 of 110 patients with lung cancer (10.9%), 5 of 54 patients with melanoma (9.2%) and 1 of 27 patients with RCC (3.7%). In the multivariable analysis, symptomatic VTEs in patients treated with immunotherapy were associated with worse OS (3.6 vs 19.1 months for symptomatic VTEs occurrence vs no occurrence respectively), with statistically significant differences (HR=2.4 (95%IC: 1.2-4.8) p value: 0.01). ConclusionsThe incidence of VTEs in cancer patients receiving immunotherapy in our sample appears to be consistent with the incidence previously reported. Symptomatic VTEs in cancer patients were associated with worsened survival. Further and prospective studies are needed to derive definitive conclusions. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

The Perioperative Continuation of Aspirin in Patients Undergoing Arthroscopic Surgery of the Knee

Background: The perioperative withdrawal of aspirin increases the risk of cardiac, neurologic, and vascular thromboembolic events. The safety of continuing aspirin in patients undergoing knee arthroscopy is unknown. Hypothesis: Perioperative continuation of aspirin does not increase surgical complications or worsen outcomes in patients 50 years of age and older undergoing knee arthroscopy. Study Design: Cohort study; Level of evidence, 3. Methods: This is a single-center, institutional review board–approved, prospective matched dual-cohort study comparing the surgical complication rates and postoperative outcomes of patients taking daily aspirin with those of unmedicated controls. Ninety patients who were 50 years of age or older and taking 81 mg or 325 mg daily aspirin were matched to 90 controls. Patients were matched on age, surgery type, and the use of a tourniquet. A complication was defined as bleeding, wound dehiscence, or wound infection requiring reoperation. Postoperative outcome measures including hematoma formation, extent of ecchymosis (mm), visual analog scale (VAS) scores for pain and swelling, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were collected preoperatively and postoperatively (10-14 days and 4-6 weeks). Results: There were no complications (0%) in either cohort. There was no difference in hematoma formation (aspirin, 1.8%; controls, 2.4%; P = .79), incidence of ecchymosis (aspirin, 17%; controls, 21%; P = .70), or the average extent of ecchymosis (aspirin, 124.6 mm; controls, 80.3 mm; P = .36) between patients taking aspirin and controls. There was no significant difference in pre- or postoperative knee range of motion between controls and patients taking aspirin. The KOOS subscores and VAS pain scores were similar between patients taking aspirin and controls at baseline and at follow-up. Conclusion: The perioperative continuation of daily aspirin in patients 50 years of age and older undergoing arthroscopic procedures of the knee is safe and does not result in an increased rate of bleeding or wound complications requiring reoperation. Continued aspirin use in patients 50 years of age and older had no significant effect on postoperative physical examination measures or patient-rated outcome scores.

Risk for vascular thromboembolic events (VaTEs) in patients (pts) with advanced urinary tract cancer (aUTC) treated with chemotherapy.

383 Background: Venous thromboembolism (VTE) is a frequent complication of cancer or its treatment. Khorana (KRS) and Compass scores are two Risk Assessment Models for VTE. However, aUTC was not adequately represented and arterial events were not included, in these models. Methods: Data from pts with aUTC treated with at least one line of chemotherapy in our institution were analyzed. VaTE definition included: DVT and PE defined as venous events and peripheral arterial thrombosis or embolus, ischemic stroke and coronary events, grouped as arterial events. The association of baseline and treatment-related factors with the development of VaTE was assessed using competing-risk regressions. According to the results of our multivariate analysis we stratified patients according to the number of the identified risk factors. Results: 354 aUTC pts treated between 4/1995 and 9/2015 entered our study. 53% of pts had received cisplatin and 42% carboplatin-based regimens. 44 pts (12.4%) suffered 45 VaTEs (13 arterial, 32 venous) within a median time of 3.3 months. The cumulative and 6-month incidence was 14.8% (95% CI: 10.9-19.4) and 9.7% (95% CI: 6.8-13.1), [venous 10.5% (95% CI: 7.3-14.3)/7.5% (95% CI: 5-10.7); arterial 5.3% (95% CI: 2.8-9)/2.7% (95% CI: 1.3-5), respectively]. No association of the KRS and the COMPASS score with the incidence of VaTEs was observed. In the univariate and multivariate analysis, cumulative VaTE incidence was significantly increased in pts with “peripheral arterial disease (PAD) or history of VΤE” (adjusted SHR: 3.29; 95% CI: 1.65-6.55; p=0.001) and pts with other solid tumor (SHR: 2.20; 95% CI: 1.05-4.62; p=0.038). There was a strong correlation between the number of risk factors and the risk for VaTE development (p&lt;0.001). Patients with 1 or 2, vs 0 factors had a 3-fold increased risk [cumulative incidence was 10.9% (95% CI: 7.4.-15.2) and 30.2% (95% CI: 18.4-42.8), respectively; SHR: 3.01 95% CI: 1.65-5.51]. Conclusions: Development of tumor-specific algorithms for the risk of vascular events is supported by our results. Pts with aUTC and a history of VTE, PAD and other solid tumor have a very high risk for VaTE. The role of prophylaxis should be prospectively studied.

Comparing the vascular thromboembolic events following arteriovenous fistula in Chinese population with end-stage renal diseases receiving Clopidogrel versus Beraprost sodium therapy: a retrospective cohort study

BackgroundTo assess the time to first on-study vascular thromboembolic events (VTEs) of clopidogrel (CL) or beraprost sodium (BPS) in Chinese population with end-stage renal disease (ESRD) treated with arteriovenous fistula (AVF) surgery.MethodsFrom Jan 2009 to May 2015, 346 ESRD cases suffering an AVF surgery and undergoing oral administration of 75 mg CL (initial dose of 300 mg), 1 time/day, for 4 weeks or 40 μg BPS, 3 times/day, for 4 weeks were retrospectively assessed. The primary outcome was time to first on-study VTE.ResultsIn total, 222 ESRD cases (CL, n = 112; BPS, n = 110) were assessed, with a median follow-up time of 38.1 months (range, 37–40 months). The mean time to first on-study VTE was 1.2 weeks (0.5–2.3) and 1.8 weeks (1.2–3.8) for CL and BPS, respectively (HR 0.27, 95% CI 0.16–1.45; P = 0.00). An increased incidence of VTEs was found during the 1th-month follow-up, with rates of 14.2 and 5.5% for CL and BPS, respectively (P = 0.03). The difference persisted over time, with rates of 24.1 and 11.8% at final follow-up, respectively (P = 0.02).ConclusionCL with an increased risk of VTEs tended to have a VTE within the 1st month after cessation compared with BPS.

Beraprost sodium versus clopidogrel for preventing vascular thromboembolic events of arteriovenous fistula in uraemic patients: a retrospective study with a mean 3-year follow-up

ObjectiveThis study aimed to evaluate the efficacy of beraprost sodium (BPS) or clopidogrel (CL) using vascular thromboembolic events (VTEs) of arteriovenous fistula as a primary endpoint in patients with end-stage renal disease (ESRD) undergoing arteriovenous fistula surgery.MethodsWe performed a multicentre, retrospective cohort study from August 2012 to August 2016. We studied patients with ESRD who underwent arteriovenous fistula surgery and received peroral administration of 40 µg BPS, three times per day, for 1 month, or 75 mg CL (initial dose of 300 mg), one time per day, for 1 month. The time to first on-study VTE was the primary endpoint.ResultsThe BPS-treated cohort had a significantly delayed time to first VTE compared with the CL-treated cohort (hazard ratio 0.33, 95% confidence interval 0.18–0.56). An increased incidence of VTEs was detected in the 1-month follow-up, with rates of 2.4% and 8.7% for BPS and CL, respectively. This difference persisted over time, with rates of 8.0% and 18.1% at the final follow-up, respectively.ConclusionCL-treated patients with ESRD have a greater risk of VTEs compared with BPS-treated patients. CL-treated patients also tend to experience a VTE within the first month after cessation of oral administration.

Risk factors associated with mortality from vascular thromboembolic events in patients diagnosed with non-small cell lung cancer: a population-based analysis.

Lung cancer patients are at increased risk for vascular events possibly due to cancer induced hypercoagulation. The purpose of this study was to evaluate risk factors associated with the mortality from vascular thromboembolic events in patients diagnosed with non-small cell lung cancer (NSCLC). Retrospective population-based analysis. We used Surveillance, Epidemiology and End Results Program for 2004-13 and evaluated 199 337 patients with NSCLC. Univariate and multivariate subdistribution hazard regression models were used to identify potential risk factors for mortality from vascular thromboembolic events. Stratification analysis against clinical stage was performed to determine if the severity of the disease influenced the identified associations. Multivariate Cox regression analysis demonstrated that increased risk of mortality due to vascular thromboembolic events was associated with age, black race, non-adenocarcinoma histology, surgical treatment alone (all, P < 0.001) and north central region of SEER registry (P = 0.003). Female gender (P < 0.001), Asian or Pacific Islander race (P = 0.001), multiple co-existing primary cancers and late cancer stages (both, P < 0.001) were associated with significantly lower risk of mortality due to vascular thromboembolic events. The significant predictors of mortality from the vascular thromboembolic event were dependent on the stages of the disease. Risk factors associated with mortality from the vascular thromboembolic events in NSCLC patients identified in this study can promote awareness and may help to identify groups of patients that can benefit from anti-thrombotic prophylaxis measures.

MOrtality and infectious complications of therapeutic EndoVAscular interventional radiology: a systematic and meta-analysis protocol

BackgroundEndovascular interventional radiology (EIR) is an increasingly popular, mini invasive treatment option for patient with symptomatic vascular disease. The EIR practiced by qualified hands is an effective, well-tolerated procedure that offers relief of patient’s symptoms with a low risk of complications. During acute post procedural period, immediate complications may relate to vascular access, restenosis, thromboembolic events, uterine ischemia, infection, necrosis, sepsis, ICU stay, surgical recovery, pain management, treatment failure, and death. Moreover, additional non-life-threatening complications exist, but they are not well described and represent disparate information.Methods/designA range of databases will be screened consulted to identify the relevant studies: PubMed, EMBASE, The Cochrane Library, NosoBase, and Google Scholar (to identify articles not yet indexed). Scientist librarian used Medical Subject Headings (MeSH) and free terms to construct the search strategy in PubMed. This search strategy will be adapted in other databases. Two coauthors will independently select the relevant studies, extract the relevant data, and assess the risk of bias in the included studies. Any disagreements between the two authors will be solved by a third author.DiscussionThis systematic review will provide a synthesis of EIR complications. The spotlighted results will be analyzed in order to provide a state-of-knowledge synopsis of the current evidence base in relation to the epidemiology of the infectious complications after EIR. In the event of conclusive results, our findings will serve as a reference background to assess guidelines on reality of the problem of the infections linked to endovascular interventional radiology and to formulate of assumptions and propose preventive measures, based on the results of our investigations. These propositions will aim to reduce the risk and/or the severity of these complications in the concerned population in favor a positive medical economics report. It will also aim to decrease the antibio-resistance and in fine will improve health status and security of patients.Systematic review registrationPROSPERO CRD42015025594

Treatment of Diabetic Macular Oedema – Clinical Trial Findings and Real-world Outcomes Data

In recent years, several intravitreal drug applications have become available for the treatment of diabetic macular oedema (DME). This review aims to summarise and compare available results. Based on a PubMed search, appropriate studies or reviews were evaluated. Clinical trial data suggest that the intravitreal administration of both vascular endothelial growth factor (VEGF) inhibitors and corticosteroids is effective and that overall outcomes are comparable between treatments. Sustained delivery of corticosteroids presents a less treatment-intensive alternative, potentially reducing side effects and enhancing compliance. Compared with clinical development data, recent findings from clinical practice suggest a lesser, more flexible injection frequency in VEGF inhibitors is associated with less pronounced efficacy results. In contrast, corticosteroids treatment frequency seems to correspond with pivotal trial results, reporting equal (or slightly higher or lower) treatment schedules, resulting in similar or higher efficacy values. Safety issues differ between drug classes. Corticosteroid side effects are essentially of local nature and mainly consist of intraocular pressure increases and progression of cataract, limiting their use to pseudophakic patients or those for whom alternative treatments are not effective or are inappropriate. Anti-VEGF treatment is also associated with ocular side effects, but also with reports on systemic side effects, such myocardial infarctions or vascular thromboembolic events. More long-term clinical practice data need to be generated to inform about effectiveness and safety of available therapies in specific patient populations.

2608 A retrospective study of vascular thromboembolic events (VaTEs) in patients receiving first line treatment for advanced urothelial cancer (AUC)

2608 A retrospective study of vascular thromboembolic events (VaTEs) in patients receiving first line treatment for advanced urothelial cancer (AUC)

State-of-the-art biosimilar erythropoietins in the management of renal anemia: lessons learned from Europe and implications for US nephrologists.

The European Medicines Agency (EMA), under a strictly regulated pathway, has approved several biosimilar products since 2005, including biosimilar versions of the erythropoiesis-stimulating agent (ESA) epoetin alfa since 2007. Subsequent to these approvals, the use of biosimilar epoetin alfa in the management of renal anemia has grown steadily throughout Europe. With the enactment of the US Biologics Price Competition and Innovation Act of 2009, a US Food and Drug Administration regulatory approval process for biosimilars was legalized. Thus, biosimilar erythropoietin products are expected to be available for prescription in the USA by mid-decade, presumably at a price that is competitive with the originator brand-name reference products. In this paper, we describe the status of originator and biosimilar ESAs, review the clinical development and regulatory approval of biosimilar erythropoietins in Europe, and summarize relevant efficacy and safety information of biosimilar erythropoietins in relation to their reference products to provide a background for US nephrologists as they appraise biosimilar erythropoietins as treatment options for renal anemia. Key lessons learned from Europe are that (a) EMA-approved biosimilar erythropoietins have comparable efficacy and safety profiles to their reference product erythropoietin; (b) pharmacovigilance preapproval and postapproval are critical, especially with regard to immunogenicity and vascular thromboembolic events; (c) strict preapproval and postapproval requirements must guide the regulatory pathway for biosimilars; and (d) high-quality manufacturing and production processes must be established to ensure quality biosimilar products. The availability of biosimilar erythropoietins in the USA will provide nephrologists with alternative effective, and potentially more affordable, treatment options for patients with renal anemia.

Thromboembolic Events After Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate: Exploratory Analyses of Two Randomized, Plasma-Controlled Studies

Study objective:We evaluated thromboembolic events after vitamin K antagonist reversal in post hoc analyses of pooled data from 2 randomized trials comparing 4-factor prothrombin complex concentrate (4F-PCC) (Beriplex/Kcentra) with plasma.Methods:Unblinded investigators identified thromboembolic events, using standardized terms (such as “myocardial infarction,” “deep vein thrombosis,” “pulmonary embolism,” and “ischemic stroke”). A blinded safety adjudication board reviewed serious thromboembolic events, as well as those referred by an independent unblinded data and safety monitoring board. We descriptively compared thromboembolic event and patient characteristics between treatment groups and included detailed patient-level outcome descriptions. We did not power the trials to assess safety.Results:We enrolled 388 patients (4F-PCC: n=191; plasma: n=197) in the trials. Thromboembolic events occurred in 14 of 191 patients (7.3%) in the 4F-PCC group and 14 of 197 (7.1%) in the plasma group (risk difference 0.2%; 95% confidence interval −5.5% to 6.0%). Investigators reported serious thromboembolic events in 16 patients (4F-PCC: n=8; plasma: n=8); the data and safety monitoring board referred 2 additional myocardial ischemia events (plasma group) to the safety adjudication board for review. The safety adjudication board judged serious thromboembolic events in 10 patients (4F-PCC: n=4; plasma: n=6) as possibly treatment related. There were 8 vascular thromboembolic events in the 4F-PCC group versus 4 in the plasma group, and 1 versus 6 cardiac events, respectively. Among patients with thromboembolic events, 3 deaths occurred in each treatment group. All-cause mortality for the pooled population was 13 per group. We observed no relationship between thromboembolic event occurrence and factor levels transiently above the upper limit of normal; there were no notable differences in median factor or proteins C and S levels up to 24 hours postinfusion start in patients with and without thromboembolic events.Conclusion:The incidence of thromboembolic events after vitamin K antagonist reversal with 4F-PCC or plasma was similar and independent of coagulation factor levels; small differences in the number of thromboembolic event subtypes were observed between treatment groups. [Ann Emerg Med. 2016;67:96-105.]

Primary venous thromboembolism prophylaxis in patients with solid tumors.

Our meta-analysis: ‘‘Primary venous thromboembolism prophylaxis in patients with solid tumors’’, was published on line in November 2013 [1]. We are writing to respond to comments made in a letter to the editor referencing our work. The abstracted and analyzed information in our metaanalysis was obtained independently by 2 reviewers. In the year since our initial abstraction and analysis, similar studies have found equivalent results to the question of primary thrombosis prevention in outpatients with cancer. Most recently, in a meta-analysis by DiNisio et al., including patients with all types of cancer the use of preventive low molecular weight heparin (LMWH) was associated with a reduction in venous thromboembolism (VTE) (RR 0.53, 95 % CI 0.38–0.75) [2]. This estimate is concordant with ours (OR 0.53; 95 %CI 0.41–0.70) despite small differences in methodology [1]. Note the risk ratio and odd ratio pooled point estimate were the same. Indeed, odd ratio is known to be an adequate estimate of risk ratio when the events are not very common [3]. In meta-analyses, due to mathematical advantages odds ratio are often used over risk ratios to standardize results of different trials [4], as we elected to do in ours. Although we acknowledge that there are important differences in the interpretation of risk ratios and odds ratios, and that the appropriateness of which to use depends on study design, our use of odd ratios was adequate. Tun adequately noted that 2 studies included arterial events in the definition of vascular thromboembolic events. Arterial events represented the minority of outcomes [5, 6]. However, if we exclude from our pooled analysis FRAGMEN and PROTECHT, the overall interpretation still translates into a significant reduction of VTE among patients with cancer who receive LMWH (OR 0.6; 95 %CI 0.42–0.9). Tun also argues that it was not appropriate to include a trial including upper extremity catheter associated thrombosis. Most clinicians will agree that an upper extremity deep vein thrombosis (DVT) is a concerning event regardless of the triggering event, as they convey a risk of pulmonary embolism, recurrent DVT and postthrombotic syndrome. Indeed, in the study by Young et al. two of the catheter related events were pulmonary embolisms, and four involved the superior vena cava [7]. In addition, we did provide estimates excluding catheter associated thrombosis. Although the trial by Young et al. was designed to evaluate a prophylactic regime to prevent catheter associated thrombosis (CAT) in cancer patients, they report all thrombotic events CAT and non-CAT, and those were the events included in our meta-analysis. Other studies included in our meta-analysis did not exclude CAT in the definition of their outcomes, for this reason and considering that CAT are prevalent in cancer patients we did not exclude them either. Finally, in patients with cancer it is recommended to treat catheter associated thrombosis with the same agents, intensity and duration as any other thrombosis [8]. This is a response to Letter to the Editor (doi: 10.1007/s11239-0141138-6). Original Article to this reply can be found at doi: 10.1007/ s11239-013-1014-9.