Risk stratification for predicting recurrent venous thromboembolism after discontinuation of anticoagulation: a post hoc analysis of a French prospective multicentre study.

BACKGROUND: We aimed to validate and to refine current recurrent venous thromboembolism (VTE) risk classification. METHODS: We performed a post hoc analysis of a multicentre cohort including 1881 patients with a first symptomatic VTE prospectively followed after anticoagulation discontinuation. The primary objective was to validate the International Society of Thrombosis and Haemostasis (ISTH) risk classification in predicting recurrence risk. The secondary objective was to evaluate a refined ISTH classification based on the recurrence risk estimate for each individual risk factor. RESULTS: During a 4.8-year median follow-up after anticoagulation discontinuation, symptomatic recurrent VTE occurred in 230 patients (12.2%). Based on the ISTH classification, patients with unprovoked VTE or VTE with minor or major persistent risk factors had a 2-fold increased recurrence risk compared with those with VTE and major transient risk factors. Recurrence risk was not increased in patients with minor transient factors (hazard ratio (HR) 1.31, 95% CI 0.84-2.06). Individual risk factors analysis identified hormone-related VTE (pregnancy: HR 0.26, 95% CI 0.08-0.82; oestrogens: HR 0.25, 95% CI 0.14-0.47) and amyotrophic lateral sclerosis (HR 5.84, 95% CI 1.82-18.70). After reclassification of these factors as major transient for the former and major persistent for the latter, the modified ISTH classification allowed us to accurately discriminate between patients at low risk of recurrence (i.e. with major transient risk factors) and those at high risk of recurrence (i.e. without major transient risk factors). CONCLUSIONS: Among patients who stopped anticoagulation after a first VTE, a refined ISTH classification based on recurrence risk intensity of individual factors allowed discrimination between patients at low recurrence risk, including hormonal exposure in women, and patients at high recurrence risk.

Randomised controlled trial of a prognostic assessment and management pathway to reduce the length of hospital stay in normotensive patients with acute pulmonary embolism.

BACKGROUND: The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown. METHODS: We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes. RESULTS: Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7-4.2 days) in the intervention group and 6.1 days (IQR 5.7-6.5 days) in the control group (p<0.001). The mean total cost of prognostic tests was EUR 174.76 in the intervention group, compared with EUR 233.12 in the control group (mean difference EUR -58.37, 95% CI EUR -84.34- to -32.40). The mean total hospitalisation cost per patient was EUR 2085.66 in the intervention group, compared with EUR 3232.97 in the control group (mean difference EUR -1147.31, 95% CI EUR -1414.97- to -879.65). No significant differences were observed in 30-day readmission (4.0% versus 4.8%), all-cause mortality (2.4% versus 2.0%) or PE-related mortality (0.8% versus 1.2%) rates. CONCLUSIONS: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE.

Association between obstructive sleep apnea and venous thromboembolism recurrence: results from a French cohort.

BACKGROUND: Growing evidence suggests the relationship between obstructive sleep apnea (OSA) and venous thromboembolism (VTE). Few studies focused on VTE recurrence risk associated with OSA after anticoagulation cessation. METHODS: In a prospective cohort study, patients with documented VTE, were followed for an indefinite length of time and VTE recurrence were documented and adjudicated. The primary outcome was recurrent VTE after anticoagulation discontinuation. Secondary outcomes included all-cause mortality and the clinical presentation of VTE. Univariable and multivariable analyses were performed to identify risk factors for recurrence and mortality. RESULTS: Among the 2109 patients with documented VTE included, 74 patients had moderate to severe OSA diagnosis confirmed by home sleep test or polysomnography. During a median follow-up of 4.8 (interquartile range 2.5-8.0) years recurrent VTE occurred in 252 patients (9 with OSA and 243 without OSA). The recurrence risk in the univariable and multivariable analysis was not increased in patients with OSA, regardless of the time of diagnosis (before or after index VTE or pooled). VTE phenotype was significantly more often PE with or without associated deep vein thrombosis in the first event and recurrence for OSA patients compared to non-OSA patients. The risk of death was not increased in the OSA population compared to non-OSA patients in multivariable analysis. CONCLUSIONS: In patients with OSA and VTE, the risk of all-cause mortality and VTE recurrence after anticoagulation discontinuation was not increased compared to non-OSA patients.

Risk of recurrent venous thromboembolism and bleeding in patients with interstitial lung disease: a cohort study.

Interstitial lung disease (ILD) encompasses various parenchymal lung disorders, which has the potential to increase the risk of venous thromboembolism (VTE). To evaluate, in patients with ILD and VTE, the risk of recurrent VTE during follow-up after stopping anticoagulation. This was a cohort of patients with a first VTE recruited between 1997 and 2015. The primary outcome was adjudicated fatal or nonfatal recurrent VTE after stopping anticoagulation. Main secondary outcomes were major or clinically relevant non-major bleeding under anticoagulation. Among 4314 patients with VTE, 50 had ILD diagnosed before VTE. Of these, anticoagulation was stopped in 30 patients after a median duration of 180 days and continued indefinitely in 20 patients. During a median follow-up of 27.8 months after anticoagulation discontinuation, recurrent VTE occurred in 15 on 30 patients (annual incidence of 19.2 events per 100-person-years [95%CI 12.0-29.3], case-fatality rate of 6.7% [95%CI 1.21-29.8]). The risk of recurrence was threefold higher when VTE was unprovoked and case-fatality rate of recurrence was increased by 3 when VTE index was PE. During the anticoagulant period, (median duration of 8.6 months), 6 patients had a major or clinically relevant bleeding (annual incidence of 7.3 events per 100-person-years [95%CI 3.4-15.1], case-fatality rate of 16.7% [95%CI 3.0-56.4]). In patients with ILD, the risk of recurrent VTE after stopping anticoagulation and the risk of bleeding under anticoagulation were very high. Our results suggest that anticoagulation should not be prolonged beyond 3-6 months of anticoagulation in most of cases.

Prevalence of Pulmonary Embolism Among Patients With COPD Hospitalized With Acutely Worsening Respiratory Symptoms.

IMPORTANCE: The prevalence of pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acutely worsening respiratory symptoms remains uncertain. OBJECTIVE: To determine the prevalence of pulmonary embolism in patients with COPD admitted to the hospital for acutely worsening respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS: Multicenter cross-sectional study with prospective follow-up conducted in 7 French hospitals. A predefined pulmonary embolism diagnostic algorithm based on Geneva score, D-dimer levels, and spiral computed tomographic pulmonary angiography plus leg compression ultrasound was applied within 48 hours of admission; all patients had 3-month follow-up. Patients were recruited from January 2014 to May 2017 and the final date of follow-up was August 22, 2017. EXPOSURES: Acutely worsening respiratory symptoms in patients with COPD. MAIN OUTCOMES AND MEASURES: The primary outcome was pulmonary embolism diagnosed within 48 hours of admission. Key secondary outcome was pulmonary embolism during a 3-month follow-up among patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulant treatment. Other outcomes were venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) at admission and during follow-up, and 3-month mortality, whether venous thromboembolism was clinically suspected or not. RESULTS: Among 740 included patients (mean age, 68.2 years [SD, 10.9 years]; 274 women [37.0%]), pulmonary embolism was confirmed within 48 hours of admission in 44 patients (5.9%; 95% CI, 4.5%-7.9%). Among the 670 patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulation, pulmonary embolism occurred in 5 patients (0.7%; 95% CI, 0.3%-1.7%) during follow-up, including 3 deaths related to pulmonary embolism. The overall 3-month mortality rate was 6.8% (50 of 740; 95% CI, 5.2%-8.8%). The proportion of patients who died during follow-up was higher among those with venous thromboembolism at admission than the proportion of those without it at admission (14 [25.9%] of 54 patients vs 36 [5.2%] of 686; risk difference, 20.7%, 95% CI, 10.7%-33.8%; P < .001). The prevalence of venous thromboembolism was 11.7% (95% CI, 8.6%-15.9%) among patients in whom pulmonary embolism was suspected (n = 299) and was 4.3% (95% CI, 2.8%-6.6%) among those in whom pulmonary embolism was not suspected (n = 441). CONCLUSIONS AND RELEVANCE: Among patients with chronic obstructive pulmonary disease admitted to the hospital with an acute worsening of respiratory symptoms, pulmonary embolism was detected in 5.9% of patients using a predefined diagnostic algorithm. Further research is needed to understand the possible role of systematic screening for pulmonary embolism in this patient population.

Derivation and validation of a clinical prediction rule for thrombolysis-associated major bleeding in patients with acute pulmonary embolism: the BACS score.

BACKGROUND: Improved prediction of the risk of major bleeding in patients with acute pulmonary embolism (PE) receiving systemic thrombolysis is crucial to guide the choice of therapy. METHODS: The study included consecutive patients with acute PE who received systemic thrombolysis in the RIETE registry. We used multivariable logistic regression analysis to create a risk score to predict 30-day major bleeding episodes. We externally validated the risk score in patients from the COMMAND VTE registry. We also compared the newly created risk score against the Kuijer and RIETE scores. RESULTS: Multivariable logistic regression identified four predictors for major bleeding: recent major Bleeding (3 points), Age >75 years (1 point), active Cancer (1 point), and Syncope (1 point) (BACS). Among 1172 patients receiving thrombolytic therapy in RIETE, 446 (38%) were classified as having low-risk (none of the variables present, 0 points) of major bleeding according to the BACS score, and the overall 30-day major bleeding rate of this group was 2.9% (95% CI, 1.6-4.9%), compared with 44% (95% CI, 14-79%) in the high-risk group (>3 points). In the validation cohort, 51% (149/290) of patients were classified as having low-risk, and the overall 30-day major bleeding rate of this group was 1.3%. In RIETE, the 30-day major bleeding event rates in the Kuijer and RIETE low-risk stratum were 5.3% and 4.4%, respectively. CONCLUSIONS: The BACS score is an easily applicable aid for prediction of the risk of major bleeding in the population of PE patients who receive systemic thrombolysis.

Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism: A Prospective Cohort Study.

Background: Pulmonary embolism (PE) is associated with increased risk for ischemic stroke, but the underlying mechanism remains unclear. The authors hypothesized that paradoxical embolism through patent foramen ovale (PFO) should be the main mechanism. Objective: To determine the frequency of recent ischemic stroke in patients with symptomatic PE according to whether PFO was detected. Design: Prospective cohort study with masked assessment of stroke outcomes. (ClinicalTrials.gov: NCT01216423). Setting: 4 French hospital centers. Participants: 361 consecutive patients with symptomatic acute PE from 13 November 2009 through 21 December 2015. Intervention: Systematic contrast transthoracic echocardiography (TTE) and cerebral magnetic resonance imaging (MRI) within 7 days after enrollment. Measurements: Recent symptomatic or silent ischemic stroke was diagnosed on the basis of clinical examination and cerebral MRI showing a hypersignal on the trace diffusion-weighted image with reduction or pseudonormalization of apparent diffusion coefficient. Results: Contrast TTE was conclusive in 324 of 361 patients and showed PFO in 43 patients (13%). The median age was 66 years (interquartile range, 54 to 77 years). In total, 51% of patients (145/284) had associated deep venous thrombosis, 91% (279/306) had cardiovascular risk factors, and 10% (16/151) presented with arrhythmia (no difference between PFO and non-PFO groups). Cerebral MRI was conclusive in 315 patients. Recent ischemic stroke was more frequent in the PFO group than in the non-PFO group (9 of 42 patients [21.4%] vs. 15 of 273 patients [5.5%]; difference in proportions, 15.9 percentage points [95% CI, 4.7 to 30.7 percentage points]). Limitation: Because of inconclusive contrast TTE or MRI, 46 patients were excluded from analysis. Conclusion: Frequency of recent ischemic stroke in patients with symptomatic PE was higher in patients with PFO than in those without PFO. This finding supports the hypothesis that paradoxical embolism is an important mechanism of ischemic stroke in patients with PFO. Primary Funding Source: French Ministry of Health.

Effect of Early Initiation of Varenicline on Smoking Cessation in COPD Patients Admitted for Exacerbation: The Save Randomized Clinical Trial.

Our main objective was to demonstrate that, in smoker patients hospitalised for Chronic Obstructive Pulmonary Disease (COPD) exacerbation, early initiation of varenicline during 12 weeks, combined with an intensive counselling, is associated with a higher continuous abstainers rate (CAR) at one year as compared to intensive counselling alone. In this multicenter, prospective, double-blind, randomised study, 81 smoking COPD patients hospitalised for an acute exacerbation for at least 24 h were allocated to receive either varenicline (n = 42) or placebo (n = 39) for 12 weeks, in association with an intensive counselling in the 2 groups, and followed up for 40 weeks. The primary outcome was CAR at week 52. Secondary outcomes included CAR at week 12 and 26, partial abstinence rate (PAR) at week 12, 26 and 52, nicotinic substitute consumption and adverse events. At week 52, CAR was not different in placebo and varenicline groups (25.6%). At week 12, CAR was significantly higher in the varenicline group (50%) as compared to placebo group (27%) (p = 0.041). Nicotine consumption was significantly higher at week 52 in the placebo group (55.3%) as compared to the varenicline group (24.4%) (p = 0.005). There was no significant difference in PAR at week 12, 26 and 52; the frequency of adverse events was similar between the two groups. Among active smoker COPD patients with exacerbation, 12-week varenicline associated with intensive counselling for smoking cessation increased the rate of continuous abstainers as compared to placebo. However, benefit was not maintained after varenicline discontinuation.Clinical Trials Registration: URL: http://www.controlled-trials.com. Unique identifier: NCT01694732.

Risk of recurrent venous thromboembolism in COPD patients: results from a prospective cohort study.

We aimed to assess the risk of recurrent venous thromboembolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) following cessation of anticoagulation therapy.In a prospective cohort of 1468 patients with a documented episode of VTE, followed for up to 5 years after cessation of anticoagulation therapy, the diagnosis of COPD was confirmed in 136. The main outcome was recurrent VTE. The secondary outcome was overall mortality. Univariate and multivariate analyses were performed to identify the risk factors of recurrence.Of the 1468 patients included, recurrent VTE was observed in 306 (34 with COPD and 272 without) during a median follow-up period of 36.5 months. The incidence rate of recurrent VTE was 9.1% (95% CI 6.5-12.8) for COPD patients and 7.0% (95% CI 6.2-7.9) for non-COPD patients. COPD was not associated with an increased risk of VTE recurrence on univariate or multivariate analyses (hazard ratio: 1.0 (95% CI 0.7-1.4)). The risk of death, adjusted for demographic and clinical characteristics, showed no increase in COPD patients, as compared to non-COPD patients.In patients with COPD who had an acute episode of VTE, the risk of recurrent VTE was not any higher than that in non-COPD patients.

Venous thromboembolism and amyotrophic lateral sclerosis: the Venous Thrombo-Embolism and Sclerosis Lateral Amyotrophic study.

Background: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease. Given the inflammatory nature of ALS and the high number of ALS-related clinical circumstances (eg, prolonged immobilization and infections), patients with ALS may have a high risk of venous thromboembolism (VTE). Objectives: To determine the annual incidence rate of VTE and the predictors of VTE in patients with ALS. Methods: We analyzed a prospective cohort of patients with ALS diagnosed between 2009 and 2019 followed in the Brest University Hospital ALS Centre. Results: Among 227 patients with ALS, VTE occurred in 19 patients during a median follow-up period of 717 days (IQR, 488-1308), yielding an annual incidence rate of 2.93% (95% CI, 1.88%-4.53%). Predictors for VTE were a family history of VTE (hazard ratio [HR], 15.24; 95% CI, 1.72-134.84; P = .01), the presence of noninvasive ventilation at ALS diagnosis (HR, 6.98; 95% CI, 1.09-44.59; P = .04) and a short time (ie, <213 days) between first symptoms and ALS diagnosis (HR, 5.48; 95% CI, 1.57-19.11; P = .01). Recurrent VTE occurred within 3 months after stopping anticoagulation in 5 patients (26.3%). Conclusion: The annual incidence of VTE in patients with ALS is high. Predictive factors of VTE were a VTE history, noninvasive ventilation, and a short time between first symptoms of ALS and ALS diagnosis.

Safety of the pulmonary embolism rule-out criteria rule: Findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry.

BACKGROUND: The diagnostic strategy for pulmonary embolism (PE) includes a D-dimer test when PE probability is low or intermediate, but false-positive D-dimer results are frequent and can result in an unnecessary computed tomography pulmonary angiogram. The PE rule-out criteria (PERC) rule excludes PE without D-dimer testing when pretest probability is <15%. The aim of this study was to assess the safety of the PERC rule strategy in patients included in the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry. METHODS: This retrospective cohort study used data from the RIETE registry, an ongoing, international prospective registry of patients with objectively confirmed venous thromboembolism. The primary outcome was the failure rate of the PERC strategy, represented by the proportion of PERC-negative (PERC-N) patients with a PE included in the registry. Secondary outcomes were a comparison of the clinical characteristics, treatment strategy, and outcome of PERC-N versus PERC-positive (PERC-P) patients at 3 months. RESULTS: From 2001 to 2021, a total of 49,793 patients with acute PE were enrolled in the RIETE registry. We included 48,903 in the final analysis after exclusion of 890 patients with an undetermined PERC status. Only 346 patients were PERC-N with a failure rate of 0.7% (95% confidence interval 0.6%-0.8%). PERC-N patients presented more frequently with chest pain but less often with dyspnea, syncope, or hypotension. They also had subsegmental or segmental PE more frequently, were more often treated with direct oral anticoagulants, and received mechanical or pharmacological thrombolysis less often. In addition, PERC-N patients had a lower incidence of recurrent deep vein thrombosis, major bleeding, and death attributed to PE during the 3-month follow-up. CONCLUSIONS: A low failure rate of the PERC rule was observed in the RIETE registry, thus supporting its use to safely identify patients with an unlikely probability of PE.

Venous Thromboembolism Associated with Assisted Reproductive Technology: A Systematic Review and Meta-analysis.

BACKGROUND: Hormonal exposure leads to an increased risk of venous thromboembolism (VTE) but the risk of VTE associated with assisted reproductive technology (ART) is not clearly determined. METHODS: We searched in PubMed, EMBASE, Web of Science, and the Cochrane Library databases and identified all relevant articles published up to February 1, 2021. The primary objective was to determine the frequency of VTE associated with ART. Secondary objectives were to determine (1) the risk of VTE associated with ART as compared to pregnancy without ART; (2) the risk of VTE associated with ovarian hyperstimulation syndrome (OHSS); and (3) to determine potential risk factors of VTE related to ART. RESULTS: Fourteen studies were included. The overall frequency of VTE associated with ART was 0.23% (95% confidence interval [CI]: 0.07-0.46). Women undergoing ART had a two- to threefold increased risk of VTE as compared to spontaneous pregnancy (relative risk [RR]: 2.66; 95% CI: 1.60-4.43). The overall frequency of VTE specifically related to OHSS was <0.001%. The risk of VTE after ART complicated by OHSS, as compared to ART without OHSS, was higher but not statistically significant (RR: 14.83; 95% CI: 0.86-255.62). Risk factors of VTE associated with ART were in vitro fertilization procedure (RR, odds ratio [OR], and hazard ratio varying from 1.77, 95% CI: 1.41-2.23 to 4.99, 95% CI: 1.24-20.05), hyperhomocysteinemia (OR: 15.2; 95% CI: 2.0-115.0), polycystic ovarian syndrome (PCOS) (RR: 4.8; 95% CI: 1.7-13.4), successful ART leading to pregnancy (OR: 13.94; 95% CI: 1.41-137.45). CONCLUSION: Further large prospective studies on risk factors of VTE in women undergoing ART are needed in order to optimize thromboprophylaxis in this context.

Pulmonary embolism diagnostic strategies in patients with COPD exacerbation: Post-hoc analysis of the PEP trial.

BACKGROUND: The prevalence of pulmonary embolism (PE) is approximately 11-17 % in patients with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The optimal diagnostic strategy for PE in these patients remains undetermined. AIMS: To evaluate the safety and efficacy of standard (revised Geneva and Wells PE scores combined with fixed D-dimer cut-off) and computed tomography pulmonary angiogram (CTPA)-sparing diagnostic strategies (ADJUST-PE, YEARS, PEGeD, 4PEPS) in patients with AE-COPD. METHOD: Post-hoc analyses of data from the multicenter prospective PEP study were performed. The primary outcome was the diagnostic failure rate of venous thromboembolism (VTE) during the entire study period. Secondary outcomes included diagnostic failure rate of PE and deep venous thrombosis (DVT), respectively, during the entire study period and the number of CTPA needed per diagnostic strategy. RESULTS: 740 patients were included. The revised Geneva and Wells PE scores combined with fixed D-dimer cut-off had a diagnostic failure rate of VTE of 0.7 % (95%CI 0.3 %-1.7 %), but >70.0 % of the patients needed imaging. All CTPA-sparing diagnostic algorithms reduced the need for CTPAs (-10.1 % to -32.4 %, depending on the algorithm), at the cost of an increased VTE diagnosis failure rate of up to 2.1 % (95%CI 1.2 %-3.4 %). CONCLUSION: Revised Geneva and Wells PE scores combined with fixed D-dimer cut-off were safe, but a high number of CTPA remained needed. CTPA-sparing algorithms would reduce imaging, at the cost of an increased VTE diagnosis failure rate that exceeds the safety threshold. Further studies are needed to improve diagnostic management in this population.

Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial.

Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients. Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight-adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707). Findings: Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P = 0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P = 0.034). Interpretation: In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens. Funding: French Ministry of Health, CAPNET, Grand-Est Region, Grand-Nancy Métropole.

Early heart rate variability evaluation enables to predict ICU patients' outcome.

Heart rate variability (HRV) is a mean to evaluate cardiac effects of autonomic nervous system activity, and a relation between HRV and outcome has been proposed in various types of patients. We attempted to evaluate the best determinants of such variation in survival prediction using a physiological data-warehousing program. Plethysmogram tracings (PPG) were recorded at 75 Hz from the standard monitoring system, for a 2 h period, during the 24 h following ICU admission. Physiological data recording was associated with metadata collection. HRV was derived from PPG in either the temporal and non-linear domains. 540 consecutive patients were recorded. A lower LF/HF, SD2/SD1 ratios and Shannon entropy values on admission were associated with a higher ICU mortality. SpO2/FiO2 ratio and HRV parameters (LF/HF and Shannon entropy) were independent correlated with mortality in the multivariate analysis. Machine-learning using neural network (kNN) enabled to determine a simple decision tree combining the three best determinants (SDNN, Shannon Entropy, SD2/SD1 ratio) of a composite outcome index. HRV measured on admission enables to predict outcome in the ICU or at Day-28, independently of the admission diagnosis, treatment and mechanical ventilation requirement.Trial registration: ClinicalTrials.gov identifier NCT02893462.

Risk factors of arterial thrombotic events after unprovoked venous thromboembolism, and after cancer associated venous thromboembolism: A prospective cohort study.

INTRODUCTION: The increased risk of arterial thrombotic (ATE) after VTE, particularly when they are unprovoked or cancer-associated has been established. However, the risk factors of ATE after these VTE remain unclear. MATERIAL AND METHODS: Using cause-specific hazard regression models, we determined risk factors of ATE (myocardial infarction, ischemic stroke, acute limb ischemia, digestive tract ischemia, or renal ischemia) in 2242 patients with unprovoked VTE and in 914 patients with cancer-associated VTE from a multi-center prospective cohort. RESULTS: Of patients with unprovoked-VTE, 174 developed ATE (7.8%, incidence: 1.26 per 100 patient-years) during follow-up (median: 68 months). Among patients with cancer-associated VTE, 57 developed ATE (6.2%, incidence: 1.98 per 100 patient-years) during follow-up (median: 30 months). After multivariable analysis, the identified risk factors of ATE in patients with unprovoked-VTE were age > 65 years (vs. <50 years, HR 2.59, 95% CI: 1.56-4.29), past history of symptomatic atherosclerosis (HR 2.11, 95% CI: 1.40-3.19), and treatment with low molecule weight heparin (vs. vitamin K antagonists, HR: 2.26, 95% CI: 1.13-4.52). In patients with cancer-associated VTE, the identified risk factors of ATE were: past history of symptomatic atherosclerosis (HR: 3.13, 95% CI: 1.72-5.67), and ongoing anticoagulation at the diagnosis of VTE (HR: 2.77, 95% CI: 1.07-7.22). CONCLUSIONS: The risk of ATE after unprovoked VTE and after cancer-associated VTE, is determined by some classic cardiovascular risk factors and appears to be influenced by anticoagulant treatment introduced for VTE, as well as the presence or absence of ongoing anticoagulation at the diagnosis of VTE.

Anticoagulation for VTE: Impact on the Risk of Major Adverse Cardiovascular Events.

BACKGROUND: It was recently established that patients who developed VTE are at increased risk of major adverse cardiovascular events (MACE) compared with the general population. However, whether the anticoagulation used for VTE influences the risk of MACE remains undescribed. RESEARCH QUESTION: Does the anticoagulant treatment for VTE affect the risk of subsequent MACE? STUDY DESIGN AND METHODS: This study included patients from a large prospective cohort who received only one family of anticoagulant treatment after the acute phase of VTE, including vitamin K antagonist (VKAs) and direct oral anticoagulants (DOACs). MACE included nonfatal acute coronary syndrome, nonfatal stroke, and all-cause death. The secondary outcome, MACE-2, included cardiovascular death instead of all-cause death. Cox proportional and Fine-Gray models served to study the relationship between anticoagulation characteristics and the risk of outcomes. RESULTS: A total of 3,790 patients (47.2% male; mean age, 60.48 years) were included. A total of 1,228 patients (32.4%) were treated for 0 to 3 months (median in overall population, 6 months). Compared with these patients, those treated for 3 to 12 months (hazard ratio [HR], 0.64; 95% CI, 0.54-0.76) or > 12 months (HR, 0.47, 95% CI, 0.39-0.56) had a significant reduced risk of MACE following adjustment for confounders. Findings were similar for MACE-2 (sub-HR for 3-12 months, 0.61 [95% CI, 0.47-0.79]; sub-HR > 12 months, 0.52 [95% CI, 0.39-0.68]). After adjustment for confounders, there was a reduced risk of MACE (HR, 0.53; 95% CI, 0.39-0.71) and MACE-2 (sub-HR, 0.48; 95% CI, 0.29-0.77) in patients treated with DOACs (vs VKAs). INTERPRETATION: Treatment of VTE for > 3 months is associated with a reduced risk of MACE, as is treatment with DOACs vs VKAs. These findings, which may influence the choice of anticoagulation strategies for VTE, need confirmation by randomized clinical trials.