Background: Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the... Show moreBackground: Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the cancer stage is unclear.Methods: We evaluated the risks of VTE recurrence and treatment-related major bleeding according to the cancer stage in patients with VTE and solid cancer randomised to apixaban or dalteparin in the Caravaggio study. Cancer stage was categorised by expert cancer physicians according to pre-specified criteria, and study outcomes were adjudicated by an independent committee unaware of cancer stage and treatment allocation.Results: Of the 1034 patients included in this analysis, 217 (21.0%) had localised cancer, 279 (27.0%) locally advanced cancer and 503 (48.7%) metastatic cancer. Cancer stage was undetermined in 35 patients (3.4%). VTE recurrence and major bleeding rates were 2.8% and 3.2% in patients with localised cancer, respectively. In comparison to patients with localised cancer, the VTE recurrence rate was higher in patients with locally advanced cancer (7.5%, hazard ra-tio [HR] = 2.8, 95% confidence interval [CI] = 1.1-6.9) and metastatic cancer (8.7%, HR = 3.3, CI = 1.4-7.7, CI). Patients with metastatic cancer had numerically increased major bleedings compared to those with localised cancer (5.2%, HR = 1.65, CI = 0.7-3.8). The ef-ficacy and safety of apixaban and dalteparin across patients with different cancer stages were consistent with the findings observed in the overall patients with cancer randomised in the study.Conclusions: Patients with locally advanced and metastatic cancer have a higher rate of VTE recurrence than patients with localised cancer with no statistically significant difference in treatment-related major bleeding. (c) 2022 Published by Elsevier Ltd. Show less
Background:The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, suggesting a lesser severity of illness. The clinical importance of patients with... Show moreBackground:The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, suggesting a lesser severity of illness. The clinical importance of patients with pulmonary embolism isolated to the subsegmental vessels is unknown.Objective:To determine the rate of recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation.Design:Multicenter prospective cohort study. (ClinicalTrials.gov: NCT01455818)Setting:Eighteen sites between February 2011 and February 2021.Patients:Patients with isolated subsegmental pulmonary embolism.Intervention:At diagnosis, patients underwent bilateral lower-extremity venous ultrasonography, which was repeated 1 week later if results were negative. Patients without deep venous thrombosis did not receive anticoagulant therapy.Measurements:The primary outcome was recurrent venous thromboembolism during the 90-day follow-up period.Results:Recruitment was stopped prematurely because the predefined stopping rule was met after 292 of a projected 300 patients were enrolled. Of the 266 patients included in the primary analysis, the primary outcome occurred in 8 patients, for a cumulative incidence of 3.1% (95% CI, 1.6% to 6.1%) over the 90-day follow-up. The incidence of recurrent venous thromboembolism was 2.1% (CI, 0.8% to 5.5%) and 5.7% (CI, 2.2% to 14.4%) over the 90-day follow-up in patients with single and multiple isolated subsegmental pulmonary embolism, respectively. No patients had a fatal recurrent pulmonary embolism.Limitation:The study was restricted to patients with low-risk subsegmental pulmonary embolism.Conclusion:Overall, patients with subsegmental pulmonary embolism who did not have proximal deep venous thrombosis had a higher-than-expected rate of recurrent venous thromboembolism. Show less
Background: The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, sug-gesting a lesser severity of illness. The clinical importance of patients with... Show moreBackground: The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, sug-gesting a lesser severity of illness. The clinical importance of patients with pulmonary embolism isolated to the subseg-mental vessels is unknown.Objective: To determine the rate of recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation.Design: Multicenter prospective cohort study. (ClinicalTrials. gov: NCT01455818)Setting: Eighteen sites between February 2011 and February 2021.Patients: Patients with isolated subsegmental pulmonary embolism.Intervention: At diagnosis, patients underwent bilateral lower-extremity venous ultrasonography, which was repeated 1 week later if results were negative. Patients without deep venous thrombosis did not receive anticoagulant therapy.Measurements: The primary outcome was recurrent venous thromboembolism during the 90-day follow-up period.Results: Recruitment was stopped prematurely because the predefined stopping rule was met after 292 of a projected 300 patients were enrolled. Of the 266 patients included in the pri-mary analysis, the primary outcome occurred in 8 patients, for a cumulative incidence of 3.1% (95% CI, 1.6% to 6.1%) over the 90-day follow-up. The incidence of recurrent venous throm-boembolism was 2.1% (CI, 0.8% to 5.5%) and 5.7% (CI, 2.2% to 14.4%) over the 90-day follow-up in patients with single and multiple isolated subsegmental pulmonary embolism, respec-tively. No patients had a fatal recurrent pulmonary embolism.Limitation: The study was restricted to patients with low-risk subsegmental pulmonary embolism.Conclusion: Overall, patients with subsegmental pulmonary em-bolism who did not have proximal deep venous thrombosis had a higher-than-expected rate of recurrent venous thromboembolism. Show less
Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at... Show moreIntermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure <= 110mm Hg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations. Show less
Aims The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment... Show moreAims The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment.Methods and results Normotensive patients with PE of 26 hospitals from France, Belgium, the Netherlands, and Switzerland were randomized to either triaging with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician-in-charge, taking into account the patient's opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent venous thrombo-embolism, major bleeding or all-cause death (non-inferiority analysis with 2.5% absolute risk difference as margin), and the rate of patients discharged home within 24 h after randomization (NCT02811237). From January 2017 through July 2019, 1975 patients were included. In the per-protocol population, the primary outcome occurred in 3.82% (34/891) in the Hestia arm and 3.57% (32/896) in the sPESI arm (P = 0.004 for non-inferiority). In the intention-to-treat population, 38.4% of the Hestia patients (378/984) were treated at home vs. 36.6% (361/986) of the sPESI patients (P = 0.41 for superiority), with a 30-day composite outcome rate of 1.33% (5/375) and 1.11% (4/359), respectively. No recurrent or fatal PE occurred in either home treatment arm.Conclusions For triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI had similar safety and effectiveness. With either tool complemented by the overruling of the physician-in-charge, more than a third of patients were treated at home with a low incidence of complications.[GRAPHICS]. Show less
IntroductionSymptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which... Show moreIntroductionSymptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined.MethodsIn a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) post-PE impairment' (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II-IV.ResultsConfirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up.ConclusionsCTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae. Show less
Pol, L.M. van der; Tromeur, C.; Bistervels, I.M.; Ni Ainle, F.; Bemmel, T. van; Bertoletti, L.; ... ; Artemis Study Investigators 2019
Background Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with... Show moreBackground Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with suspected pulmonary embolism undergo computed tomographic (CT) pulmonary angiography or ventilation-perfusion scanning, both of which involve radiation exposure to the mother and fetus. Whether a pregnancy-adapted algorithm could be used to safely avoid diagnostic imaging in pregnant women with suspected pulmonary embolism is unknown. Methods In a prospective study involving pregnant women with suspected pulmonary embolism, we assessed three criteria from the YEARS algorithm (clinical signs of deep-vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the d-dimer level. Pulmonary embolism was ruled out if none of the three criteria were met and the d-dimer level was less than 1000 ng per milliliter or if one or more of the three criteria were met and the d-dimer level was less than 500 ng per milliliter. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep-vein thrombosis; if the results were positive (i.e., a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism. Results A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep-vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval [CI], 0.04 to 1.2); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% CI, 35 to 44). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester. Conclusions Pulmonary embolism was safely ruled out by the pregnancy-adapted YEARS diagnostic algorithm across all trimesters of pregnancy. CT pulmonary angiography was avoided in 32 to 65% of patients. Show less
Righini, M.; Es, J. van; Exter, P.L. den; Roy, P.M.; Verschuren, F.; Ghuysen, A.; ... ; Gal, G. le 2014
