Publications by authors named "Menno V Huisman"

306 Publications

Reduced-dose intravenous thrombolysis for acute intermediate high-risk pulmonary embolism: Rationale and design of the PEITHO-3 trial.

Thromb Haemost 2021 Sep 24. Epub 2021 Sep 24.

Hopital Europeen Georges Pompidou, Paris, France.

Intermediate high-risk pulmonary embolism (PE) is characterised by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent haemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of haemodynamic 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 Trial (PEITHO)-3 study (EudraCT 2018-000816-96) is a randomised, placebo-controlled, double-blind, multicentre, 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 fulfil at least one clinical criterion of severity: systolic blood pressure ≤ 110 mmHg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, haemodynamic decompensation or PE recurrence within 30 days of randomisation. 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, haemodynamic decompensation, or stroke within 30 days; dyspnoea, functional limitation or RV dysfunction at 6 months and 2 years; and utilisation of healthcare resources within 30 days and 2 years. The study is planned to enrol 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations.
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http://dx.doi.org/10.1055/a-1653-4699DOI Listing
September 2021

Ruling out Pulmonary Embolism in Patients with (Suspected) COVID-19-A Prospective Cohort Study.

TH Open 2021 Jul 15;5(3):e387-e399. Epub 2021 Sep 15.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, South-Holland, The Netherlands.

 Diagnostic strategies for suspected pulmonary embolism (PE) have not been prospectively evaluated in COVID-19 patients.  Prospective, multicenter, outcome study in 707 patients with both (suspected) COVID-19 and suspected PE in 14 hospitals. Patients on chronic anticoagulant therapy were excluded. Informed consent was obtained by opt-out approach. Patients were managed by validated diagnostic strategies for suspected PE. We evaluated the safety (3-month failure rate) and efficiency (number of computed tomography pulmonary angiographies [CTPAs] avoided) of the applied strategies.  Overall PE prevalence was 28%. YEARS was applied in 36%, Wells rule in 4.2%, and "CTPA only" in 52%; 7.4% was not tested because of hemodynamic or respiratory instability. Within YEARS, PE was considered excluded without CTPA in 29%, of which one patient developed nonfatal PE during follow-up (failure rate 1.4%, 95% CI 0.04-7.8). One-hundred seventeen patients (46%) managed according to YEARS had a negative CTPA, of whom 10 were diagnosed with nonfatal venous thromboembolism (VTE) during follow-up (failure rate 8.8%, 95% CI 4.3-16). In patients managed by CTPA only, 66% had an initial negative CTPA, of whom eight patients were diagnosed with a nonfatal VTE during follow-up (failure rate 3.6%, 95% CI 1.6-7.0).  Our results underline the applicability of YEARS in (suspected) COVID-19 patients with suspected PE. CTPA could be avoided in 29% of patients managed by YEARS, with a low failure rate. The failure rate after a negative CTPA, used as a sole test or within YEARS, was non-negligible and reflects the high thrombotic risk in these patients, warranting ongoing vigilance.
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http://dx.doi.org/10.1055/s-0041-1735155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443402PMC
July 2021

Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: the API-CAT Study.

Thromb Haemost 2021 Sep 17. Epub 2021 Sep 17.

Unité de Recherche Clinique Innovation et Pharmacologie, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France.

Cancer-associated thrombosis (CAT) is associated with a high risk of recurrent venous thromboembolic events (VTE) that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding.The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is non-inferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism.APICAT is an international, randomized, parallel-group, double-blind, non-inferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 mg or 5 mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or non-major clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the 2-sided 95% confidence interval of the hazard ratio <2.0, 1722 patients will be randomized,assuming an up to 10% loss in total patient-years (β = 80%; α 1-sided = 0.025). This trialhas the potential to demonstrate that a regimen of extended treatment for patients with CAT beyond an initial 6 months, with a reduced apixaban dose,has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding.
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http://dx.doi.org/10.1055/a-1647-9896DOI Listing
September 2021

Risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer using edoxaban.

J Thromb Haemost 2021 Aug 29. Epub 2021 Aug 29.

Department of Vascular Medicine, Amsterdam Cardiovascular Science, Medical Centers, Amsterdam University, University of Amsterdam, Amsterdam, The Netherlands.

Background: In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients.

Objectives: To evaluate risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban.

Patients/methods: In this nested case-control study in patients with gastrointestinal cancer randomized to edoxaban in the Hokusai VTE Cancer study, cases (patients with clinically relevant gastrointestinal bleeding during treatment) were randomly matched to three controls (patients who had no gastrointestinal bleeding). Data for the 4-week period prior to bleeding were retrospectively collected. Odds ratios (ORs) were calculated in a crude conditional logistic regression model and a multivariable model adjusted for age, sex, and cancer type.

Results: Twenty-four cases and 64 matched controls were included. In the multivariable analysis, advanced cancer, defined as regionally advanced or metastatic cancer (OR 3.6, 95% CI 1.01-12.6) and low hemoglobin levels (OR 4.8, 95% CI 1.5-16.0) were significantly associated with bleeding. There was no significant difference in patients with resected tumors (OR 0.4, 95% CI 0.1-1.4), or in patients on chemotherapy (OR 1.3, 95% CI 0.5-3.5).

Conclusion: Advanced cancer and low hemoglobin levels were associated with an increased risk of gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. We were unable to identify other risk factors, mainly due to limited statistical power.
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http://dx.doi.org/10.1111/jth.15516DOI Listing
August 2021

Efficacy and safety of a 12-week outpatient pulmonary rehabilitation program in Post-PE Syndrome.

Thromb Res 2021 Oct 17;206:66-75. Epub 2021 Aug 17.

Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands. Electronic address:

Background: The Post-Pulmonary Embolism Syndrome (PPES) comprises heterogeneous entities, including chronic thromboembolic disease with/without pulmonary hypertension (CTEPH/CTEPD), and deconditioning.

Objectives: To assess underlying physiological determinants of PPES, and efficacy and safety of rehabilitation training in these patients.

Methods: 56 consecutive PE patients with persistent dyspnea and/or functional limitations despite ≥3 months of anticoagulation underwent standardized diagnostic work-up including exercise testing as part of routine practice. All diagnostic (imaging and cardiopulmonary function) tests were interpreted by a core group of experienced clinicians. A subgroup of patients without CTEPH or other treatable conditions was referred for a 12-week personalized rehabilitation program, studying changes in physical condition and patient-reported outcome measures.

Results: Persistent vascular occlusions were observed in 21/56 patients (38%) and CTEPH was confirmed in ten (18%). Regarding those without CTEPH, impaired cardiopulmonary responses were evident in 18/39 patients with available CPET data (46%), unrelated to chronic thrombi. Rehabilitation was completed by 27 patients after excluding 29 (patients with CTEPH or treatable comorbidities, refusal, ineligibility, or training elsewhere). Training intensity, PE-specific quality of life (PEmb-QoL) and fatigue (CIS) improved with a median difference of 20 W (p = 0.001), 3.9 points (p < 0.001) and 16 points (p = 0.003), respectively. Functional status (Post-VTE Functional Status Scale) improved ≥1 grade in 18 (67%) patients, and declined in one (3.7%).

Conclusions: Our findings suggest that abnormal cardiopulmonary responses to exercise are common in patients with PPES and are not limited to those with chronic thrombi. Offering pulmonary rehabilitation to patients not treated otherwise seems safe and promising.
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http://dx.doi.org/10.1016/j.thromres.2021.08.012DOI Listing
October 2021

Changes in anticoagulant prescription patterns over time for patients with atrial fibrillation around the world.

J Arrhythm 2021 Aug 10;37(4):990-1006. Epub 2021 Jul 10.

Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart and Chest Hospital Liverpool UK.

Background: Prescribing patterns for stroke prevention in atrial fibrillation (AF) patients evolved with approval of non-Vitamin K antagonist oral anticoagulants (NOACs) over time.

Objectives: To assess changes in anticoagulant prescription patterns in various geographical regions upon first approval of a NOAC and to analyze the evolution of oral anticoagulants (OACs) use over time in relation to CHADS-VASc and HAS-BLED risk profiles.

Methods: Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation GLORIA-AF) Phases II and III reported data on antithrombotic therapy for patients with newly diagnosed AF and ≥1 stroke risk factor. We focused on sites enrolling patients in both phases and reported treatment patterns for the first 4 years after initial NOAC approval.

Results: From GLORIA-AF Phases II and III, 27 432 patients were eligible for this analysis. When contrasting the first year with the fourth year of enrolment, the proportion of NOAC prescriptions increased in Asia from 29.2% to 60.8%, in Europe from 53.4% to 75.8%, in North America from 49.0% to 73.9% and in Latin America from 55.7% to 71.1%. The proportion of Vitamin K antagonists (VKAs) use decreased across all regions over time, in Asia from 26.0% to 9.8%, in Europe from 35.5% to 16.8%, in North America from 28.9% to 12.1%, and in Latin America from 32.4% to 17.8%. In the multivariable analysis, factors associated with NOAC prescription were as follows: enrolment year, type of site, region, stroke and bleeding risk scores, and type and categorization of AF.

Conclusions: During 4 years after the approval of the first NOAC, NOAC use increased, while VKA use decreased, across all regions.
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http://dx.doi.org/10.1002/joa3.12588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339088PMC
August 2021

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial.

Lancet Haematol 2021 Sep 4;8(9):e627-e636. Epub 2021 Aug 4.

Internal and Subintensive Medicine Department, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.

Background: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe.

Methods: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555).

Findings: Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1-5]) of 402 patients had at least one major bleeding event and 16 (4% [2-6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran.

Interpretation: A strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation.

Funding: German Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim.
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http://dx.doi.org/10.1016/S2352-3026(21)00203-9DOI Listing
September 2021

Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial.

Eur Heart J 2021 08;42(33):3146-3157

F-CRIN, INNOVTE, Saint-Etienne, France.

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.

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.
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http://dx.doi.org/10.1093/eurheartj/ehab373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408662PMC
August 2021

Executive Summary: Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report.

Chest 2021 Aug 2. Epub 2021 Aug 2.

Department of Medicine, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD.

Background: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.

Methods: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology.

Results: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update.

Conclusion: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.
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http://dx.doi.org/10.1016/j.chest.2021.07.056DOI Listing
August 2021

Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report.

Chest 2021 Aug 2. Epub 2021 Aug 2.

Department of Medicine, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD.

Background: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.

Methods: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology.

Results: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update.

Conclusion: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.
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http://dx.doi.org/10.1016/j.chest.2021.07.055DOI Listing
August 2021

Identification of chronic thromboembolic pulmonary hypertension on CTPAs performed for diagnosing acute pulmonary embolism depending on level of expertise.

Eur J Intern Med 2021 Jul 19. Epub 2021 Jul 19.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.

Background: Expert reading often reveals radiological signs of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic PE on computed tomography pulmonary angiography (CTPA) performed at the time of acute pulmonary embolism (PE) presentation preceding CTEPH. Little is known about the accuracy and reproducibility of CTPA reading by radiologists in training in this setting.

Objectives: To evaluate 1) whether signs of CTEPH or chronic PE are routinely reported on CTPA for suspected PE; and 2) whether CTEPH-non-expert readers achieve comparable predictive accuracy to CTEPH-expert radiologists after dedicated instruction.

Methods: Original reports of CTPAs demonstrating acute PE in 50 patients whom ultimately developed CTEPH, and those of 50 PE who did not, were screened for documented signs of CTEPH. All scans were re-assessed by three CTEPH-expert readers and two CTEPH-non-expert readers (blinded and independently) for predefined signs and overall presence of CTEPH.

Results: Signs of chronic PE were mentioned in the original reports of 14/50 cases (28%), while CTEPH-expert radiologists had recognized 44/50 (88%). Using a standardized definition (≥3 predefined radiological signs), moderate-to-good agreement was reached between CTEPH-non-expert readers and the experts' consensus (k-statistics 0.46; 0.61) at slightly lower sensitivities. The CTEPH-non-expert readers had moderate agreement on the presence of CTEPH (κ-statistic 0.38), but both correctly identified most cases (80% and 88%, respectively).

Conclusions: Concomitant signs of CTEPH were poorly documented in daily practice, while most CTEPH patients were identified by CTEPH-non-expert readers after dedicated instruction. These findings underline the feasibility of achieving earlier CTEPH diagnosis by assessing CTPAs more attentively.
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http://dx.doi.org/10.1016/j.ejim.2021.07.001DOI Listing
July 2021

Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation.

J Thromb Haemost 2021 08 14;19(8):1874-1882. Epub 2021 Jul 14.

Division of Hematology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.

Although direct-acting oral anticoagulants (DOACs) have widespread first-line use for treatment and prevention of venous thromboembolism (VTE), uncertainty remains regarding their efficacy and safety in patients with obesity. We reviewed available data for use of DOACs for VTE treatment and prevention in patients with obesity, including phase 3, phase 4, meta-analyses, and pharmacokinetic and pharmacodynamics studies. In addition, we reviewed available data regarding DOACs in bariatric surgery. We provide updated guidance recommendations on using DOACs in patients with obesity for treatment and prevention of VTE, as well as following bariatric surgery.
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http://dx.doi.org/10.1111/jth.15358DOI Listing
August 2021

Toward a tailored diagnostic standard for future diagnostic studies in pulmonary embolism: Communication from the SSC of the ISTH.

J Thromb Haemost 2021 07;19(7):1834-1835

Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.

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http://dx.doi.org/10.1111/jth.15357DOI Listing
July 2021

Low bleeding and thromboembolic risk with continued dabigatran during cardiovascular interventions: the GLORIA-AF study.

Eur J Intern Med 2021 09 11;91:75-80. Epub 2021 Jun 11.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.

Background: Prospective data on nonvitamin-K-antagonist oral anticoagulant (NOAC) management during cardiovascular interventions are limited. We therefore evaluated the safety and effectiveness of uninterrupted dabigatran therapy as well as dabigatran management during atrial fibrillation (AF)-cardioversions, AF-ablations, pacemaker implantations and coronary angiography and/or stenting procedures.

Method: GLORIA-AF is an international registry programme involving patients with newly diagnosed AF. Dabigatran users were followed for ≤2 years. The primary outcome was occurrence of stroke/systemic embolism and major bleeding ≤8 weeks after a cardiovascular intervention during uninterrupted dabigatran therapy.

Results: During the 2-year follow-up, 599 cardiovascular interventions were identified in 479 eligible patients. 412/599 (69%) interventions were performed with uninterrupted dabigatran therapy: 299/354 (84%) AF-cardioversions, 38/89 (43%) AF-ablations, 25/58 (43%) pacemaker implantations, and 50/98 (51%) coronary angiography and/or stenting procedures. During an average follow-up of 8.4 weeks after intervention, one major bleed and one systemic embolic event occurred (risk 0.25% for both outcomes; 95% confidence interval, 0.01%-1.36%).

Conclusions: More than two thirds of the interventions were performed with uninterrupted dabigatran therapy, of which most were AF-cardioversions. Uninterrupted dabigatran therapy was associated with low major bleeding and stroke/systemic embolism risk, supporting the favourable safety and effectiveness profile of dabigatran in clinical practice-based settings.
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http://dx.doi.org/10.1016/j.ejim.2021.05.020DOI Listing
September 2021

Evolution of CT findings after anticoagulant treatment for acute pulmonary embolism in patients with and without an ultimate diagnosis of CTEPH.

Eur Respir J 2021 Jun 10. Epub 2021 Jun 10.

Department of Radiology and Nuclear Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Introduction: The pulmonary arterial morphology of patients with pulmonary embolism (PE) is diverse and it is unclear how the different vascular lesions evolve after initiation of anticoagulant treatment. A better understanding of the evolution of CTPA findings after the start of anticoagulant treatment may help to better identify those PE patients prone to develop CTEPH. We aimed to assess the evolution of various thromboembolic lesions on CTPA over time after the initiation of adequate anticoagulant treatment in individual acute PE patients with and without an ultimate diagnosis of CTEPH.

Methods: We analysed the CTPA at diagnosis of acute PE (baseline) and at follow-up in 41 patients with CTEPH and 124 patients without an ultimate diagnosis of CTEPH, all receiving anticoagulant treatment. Central and segmental pulmonary arteries were scored by expert chest radiologists as normal or affected. Lesions were further sub-classified as: 1. central thrombus, 2. total thrombotic occlusion, 3. mural thrombus, 4. web or 5. tapered pulmonary artery.

Results: Central thrombi resolved after anticoagulant treatment, while mural thrombi and total thrombotic occlusions either resolved or evolved into webs or tapered pulmonary arteries. Only patients with an ultimate diagnosis of CTEPH exhibited webs and tapered pulmonary arteries on the baseline scan. Moreover, such lesions always persisted after follow-up.

Conclusion: Webs and tapered pulmonary arteries at the time of PE diagnosis strongly indicate a state of chronic PE and should raise awareness for possible CTEPH, particularly in patients with persistent dyspnea after anticoagulant treatment for acute PE.
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http://dx.doi.org/10.1183/13993003.00699-2021DOI Listing
June 2021

A meta-analysis of andexanet alfa and prothrombin complex concentrate in the treatment of factor Xa inhibitor-related major bleeding.

Res Pract Thromb Haemost 2021 May 24;5(4):e12518. Epub 2021 May 24.

Department of Hospital Pharmacy OLVG Amsterdam The Netherlands.

Background: Andexanet alfa (andexanet) and prothrombin complex concentrate (PCC) are both reversal agents for major bleeding in patients using factor Xa inhibitors (FXaIs). Our aim was to evaluate the current evidence for the effectiveness and safety of andexanet and PCC in a systematic review and meta-analysis.

Objectives: Primary objective was hemostatic effectiveness. Secondary objectives were thromboembolic event rate and mortality.

Methods: A systematic review was performed in PubMed and Embase. Studies describing the effectiveness and/or safety of PCC or andexanet in patients with major bleeding using FXaIs were included. Meta-analysis was performed using a random-effects model.

Results: Seventeen PCC studies, 3 andexanet studies, and 1 study describing PCC and andexanet were included, comprising 1428 PCC-treated and 396 andexanet-treated patients. None of the included studies had control groups, hampering a pooled meta-analysis to compare the two reversal agents. Separate analyses for andexanet and PCC were performed. In subgroup analysis, the pooled proportion of patients with effective hemostasis in studies that used Annexa-4 criteria demonstrated a hemostatic effectiveness of 0.85 (95% confidence interval [CI], 0.80-0.90) in PCC and 0.82 (95% CI, 0.78-0.87) in andexanet studies. The pooled proportion of patients with thromboembolic events was 0.03 (95% CI, 0.02-0.04) in PCC and 0.11 (95% CI, 0.04-0.18) in andexanet studies.

Conclusion: Based on the available evidence with low certainty from observational studies, PCC and andexanet demonstrated a similar, effective hemostasis in the treatment of major bleeding in patients using FXaIs. Compared to PCC, the thromboembolic event rate appeared higher in andexanet-treated patients.
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http://dx.doi.org/10.1002/rth2.12518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143276PMC
May 2021

Home Treatment Compared to Initial Hospitalization in Normotensive Patients with Acute Pulmonary Embolism in the Netherlands: A Cost Analysis.

Thromb Haemost 2021 May 26. Epub 2021 May 26.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.

Background:  Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home treatment of pulmonary embolism (PE) is associated with a cost reduction. An accurate estimation of cost savings per patient treated at home is currently lacking.

Aim:  The aim of this study was to compare health care utilization and costs during the first 3 months after a PE diagnosis in patients who are treated at home versus those who are initially hospitalized.

Methods:  Patient-level data of the YEARS cohort study, including 383 normotensive patients diagnosed with PE, were used to estimate the proportion of patients treated at home, mean hospitalization duration in those who were hospitalized, and rates of PE-related readmissions and complications. To correct for baseline differences within the two groups, regression analyses was performed. The primary outcome was the average total health care costs during a 3-month follow-up period for patients initially treated at home or in hospital.

Results:  Mean hospitalization duration for the initial treatment was 0.69 days for those treated initially at home ( = 181) and 4.3 days for those initially treated in hospital ( = 202). Total average costs per hospitalized patient were €3,209 and €1,512 per patient treated at home. The adjusted mean difference was €1,483 (95% confidence interval: €1,181-1,784).

Conclusion:  Home treatment of hemodynamically stable patients with acute PE was associated with an estimated net cost reduction of €1,483 per patient. This difference underlines the advantage of triage-based home treatment of these patients.
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http://dx.doi.org/10.1055/a-1518-1847DOI Listing
May 2021

Detection of upper extremity deep vein thrombosis by magnetic resonance non-contrast thrombus imaging.

J Thromb Haemost 2021 08 16;19(8):1973-1980. Epub 2021 Jun 16.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.

Background: Compression ultrasonography (CUS) is the first-line imaging test for diagnosing upper extremity deep vein thrombosis (UEDVT), but often yields inconclusive test results. Contrast venography is still considered the diagnostic standard but is an invasive technique.

Objectives: We aimed to determine the diagnostic accuracy of magnetic resonance noncontrast thrombus imaging (MR-NCTI) for the diagnosis of UEDVT.

Methods: In this international multicenter diagnostic study, we prospectively included patients with clinically suspected UEDVT who were managed according to a diagnostic algorithm that included a clinical decision rule (CDR), D-dimer test, and diagnostic imaging. UEDVT was confirmed by CUS or (computed tomography [CT]) venography. UEDVT was excluded by (1) an unlikely CDR and normal D-dimer, (2) a normal serial CUS or (3) a normal (CT) venography. Within 48 h after the final diagnosis was established, patients underwent MR-NCTI. MR-NCTI images were assessed post hoc by two independent radiologists unaware of the presence or absence of UEDVT. The sensitivity, specificity, and interobserver agreement of MR-NCTI for UEDVT were determined.

Results: Magnetic resonance noncontrast thrombus imaging demonstrated UEDVT in 28 of 30 patients with UEDVT and was normal in all 30 patients where UEDVT was ruled out, yielding a sensitivity of 93% (95% CI 78-99) and specificity of 100% (95% CI 88-100). The interobserver agreement of MR-NCTI had a kappa value of 0.83 (95% CI 0.69-0.97).

Conclusions: Magnetic resonance noncontrast thrombus imaging is an accurate and reproducible method for diagnosing UEDVT. Clinical outcome studies should determine whether MR-NCTI can replace venography as the second-line imaging test in case of inconclusive CUS.
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http://dx.doi.org/10.1111/jth.15394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361740PMC
August 2021

Andexanet Alfa or Prothrombin Complex Concentrate for Factor Xa Inhibitor Reversal in Acute Major Bleeding: A Systematic Review and Meta-Analysis.

Crit Care Med 2021 10;49(10):e1025-e1036

Department of Trauma Surgery, Leiden University Medical Center, Leiden, The Netherlands.

Objectives: To combine evidence on andexanet alfa and prothrombin complex concentrates for factor Xa inhibitor-associated bleeding to guide clinicians on reversal strategies.

Data Sources: Embase, Pubmed, Web of Science, and the Cochrane Library.

Study Selection: Observational studies and randomized clinical trials studying hemostatic effectiveness of andexanet alfa or prothrombin complex concentrate for acute reversal of factor Xa inhibitor-associated hemorrhage.

Data Extraction: Two independent reviewers extracted the data from the studies. Visualization and comparison of hemostatic effectiveness using Sarode et al or International Society of Thrombosis and Hemostasis Scientific and Standardization Committee criteria at 12 and 24 hours, (venous) thrombotic event rates, and inhospital mortality were performed by constructing Forest plots. Exploratory analysis using a logistic mixed model analysis was performed to identify factors associated with effectiveness and venous thromboembolic event.

Data Synthesis: A total of 21 studies were included (andexanet: 438 patients; prothrombin complex concentrate: 1,278 patients). The (weighted) mean effectiveness for andexanet alfa was 82% at 12 hours and 71% at 24 hours. The (weighted) mean effectiveness for prothrombin complex concentrate was 88% at 12 hours and 76% at 24 hours. The mean 30-day symptomatic venous thromboembolic event rates were 5.0% for andexanet alfa and 1.9% for prothrombin complex concentrate. The mean 30-day total thrombotic event rates for andexanet alfa and prothrombin complex concentrate were 10.7% and 3.1%, respectively. Mean inhospital mortality was 23.3% for andexanet versus 15.8% for prothrombin complex concentrate. Exploratory analysis controlling for potential confounders did not demonstrate significant differences between both reversal agents.

Conclusions: Currently, available evidence does not unequivocally support the clinical effectiveness of andexanet alfa or prothrombin complex concentrate to reverse factor Xa inhibitor-associated acute major bleeding, nor does it permit conventional meta-analysis of potential superiority. Neither reversal agent was significantly associated with increased effectiveness or a higher rate of venous thromboembolic event. These results underscore the importance of randomized controlled trials comparing the two reversal agents and may provide guidance in designing institutional guidelines.
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http://dx.doi.org/10.1097/CCM.0000000000005059DOI Listing
October 2021

Antithrombotic treatment pattern in newly diagnosed atrial fibrillation patients and 2-year follow-up results for dabigatran-treated patients in the Africa/Middle-East Region: Phase II results from the GLORIA-AF registry program.

Int J Cardiol Heart Vasc 2021 Jun 10;34:100763. Epub 2021 Apr 10.

Leiden University Medical Centre, Leiden, The Netherlands.

Background: Data on the epidemiology and treatment of atrial fibrillation in the Africa/Middle East region are limited, and the use of novel oral anticoagulants and their effectiveness in real-world clinical practice has not been evaluated.

Methods And Results: This study used prospectively collected data from the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation (GLORIA-AF) to describe anticoagulant use and outcomes in Africa and the Middle East. Baseline characteristics of patients newly diagnosed with nonvalvular atrial fibrillation from Lebanon (242 patients, 40.3%), Saudi Arabia (236 patients, 39.3%), United Arab Emirates (87 patients, 14.5%), and South Africa (35 patients, 5.8%) were described, and clinical outcomes were investigated for all patients in this region who received dabigatran.In newly diagnosed patients (having a diagnosis within the last three months) with nonvalvular atrial fibrillation in Africa and the Middle East, the observed uptake of non-vitamin K oral anticoagulants was high in the first years following their availability; dabigatran was the most commonly used antithrombotic agent (314/600 patients), and only 1.5% of patients did not receive any antithrombotic therapy. Use of dabigatran was associated with a high persistence rate (>88% at 24 months) and low incidence rates of stroke, myocardial infarction, major bleeding, and all-cause mortality after 2 years of follow-up.

Conclusions: Data from GLORIA-AF reveal a change in the landscape for stroke prevention in the AME region, and the results were consistent with those observed in the global GLORIA-AF registry, as well as those of randomized clinical trials. NCT01937377 (https://clinicaltrials.gov/ct2/show/NCT01937377).
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http://dx.doi.org/10.1016/j.ijcha.2021.100763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065192PMC
June 2021

Atrial fibrillation and comorbidities: Clinical characteristics and antithrombotic treatment in GLORIA-AF.

PLoS One 2021 14;16(4):e0249524. Epub 2021 Apr 14.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom.

Background: Patients with AF often have multimorbidity (the presence of ≥2 concomitant chronic conditions).

Objective: To describe baseline characteristics, patterns of antithrombotic therapy, and factors associated with oral anticoagulant (OAC) prescription in patients with AF and ≥2 concomitant, chronic, comorbid conditions.

Methods: Phase III of the GLORIA-AF Registry enrolled consecutive patients from January 2014 through December 2016 with recently diagnosed AF and CHA2DS2-VASc score ≥1 to assess the safety and effectiveness of antithrombotic treatment.

Results: Of 21,241 eligible patients, 15,119 (71.2%) had ≥2 concomitant, chronic, comorbid conditions. The proportions of patients with multimorbidity receiving non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKA) were 60.2% and 23.6%, respectively. The proportion with paroxysmal AF was 57.0% in the NOAC group and 45.4% in the VKA group. Multivariable log-binomial regression analysis found the following factors were associated with no OAC prescription: pattern of AF (paroxysmal, persistent, or permanent), coronary artery disease, myocardial infarction, prior bleeding, smoking status, and region (Asia, North America, or Europe). Factors associated with OAC prescriptions were age, body mass index, renal function, hypertension, history of cerebral ischemic symptoms, and AF ablation.

Conclusion: Multimorbid AF patients prescribed NOACs have fewer comorbidities than those prescribed VKAs. Age, AF pattern, comorbidities, and renal function are associated with OAC prescription.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249524PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046191PMC
September 2021

Adherence to direct oral anticoagulant treatment for atrial fibrillation in the Netherlands: A surveillance study.

Pharmacoepidemiol Drug Saf 2021 Aug 4;30(8):1027-1036. Epub 2021 May 4.

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

Background: Adherence to direct oral anticoagulants (DOACs) in patients with atrial fibrillation in every day practice may be less than in clinical trials.

Aims: To assess adherence to DOACs in atrial fibrillation patients in every day practice and identify predictors for non-adherence.

Methods: Individual linked dispensing data of atrial fibrillation patients who used DOACs were obtained from the Foundation for Pharmaceutical Statistics covering the Netherlands between 2012 and 2016. One year adherence to DOAC was calculated for initial DOAC as proportion of days covered (PDC) ≥80% and the association between clinical variables and adherence was assessed using logistic regression. In addition, we measured non-persistence, that is, patients who completely stopped their initial DOAC within 1 year follow-up.

Results: A total of 4797 apixaban-, 20 454 rivaroxaban- and 18 477 dabigatran users were included. The mean age was 69 years (n = 43 910), which was similar for the DOAC types. The overall proportion of patients with PDC ≥80% was 76%, which was highest for apixaban- (87%), followed by dabigatran- (80%) and rivaroxaban (69%) users. Multivariable analyses revealed that age ≤60 years, no concomitant drug use were predictors for non-adherence. Of atrial fibrillation patients who continued treatment, 97% had a PDC ≥80%, compared with only 56% for those who discontinued their DOAC treatment within 1 year.

Conclusions: Non-adherence to DOACs was associated with age ≤60 years and no concomitant drugs use. Non-adherence was higher in patients who later discontinued DOAC treatment. Results of our study support research into interventions to improve adherence.
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http://dx.doi.org/10.1002/pds.5242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360064PMC
August 2021

[Diagnosis of recurrent venous thromboembolism].

Ned Tijdschr Geneeskd 2021 03 25;165. Epub 2021 Mar 25.

LUMC, Leiden: Afd. Trombose en Hemostase.

A correct diagnosis of recurrent venous thromboembolism (VTE) is essential as patients diagnosed with a recurrence are mostly treated with lifelong anticoagulant treatment. However, the diagnosis of recurrent VTE is complex as routine diagnostic tests for suspected VTE are less accurate in patients without a prior VTE. Clinical decision rules (CDR) and D-dimer tests have a lower specificity in suspected recurrent VTE, leading to an increase in required diagnostic imaging tests. In contrast to suspected recurrent pulmonary embolism (PE), the safety of a CDR and D-dimer test in excluding recurrent deep vein thrombosis (DVT) is debated. A CDR in combination with D-dimer testing followed by computed tomography pulmonary angiography is the preferred diagnostic management for suspected recurrent PE. In suspected recurrent DVT, compression ultrasonography is the imaging technique of choice and in case of a suspected recurrent ipsilateral DVT and an inconclusive ultrasonography, magnetic resonance direct thrombus imaging is decisive.
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March 2021

Effects of concomitant administration of anticancer agents and apixaban or dalteparin on recurrence and bleeding in patients with cancer-associated venous thromboembolism.

Eur J Cancer 2021 05 26;148:371-381. Epub 2021 Mar 26.

Internal, Vascular and Emergency Medicine - Stroke Unit, University of Perugia, Perugia, Italy.

Background: Whether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism (VTE) is undefined. The pharmacological interaction between anticancer agents and direct oral anticoagulants is perceived as a concern.

Methods: We evaluated the effects of concomitant administration of anticancer agents on recurrent VTE, major bleeding and death in patients with cancer-associated VTE randomised to receive apixaban or dalteparin in the Caravaggio study.

Results: Anticancer agents were concomitantly given to 336 patients (58.3%) treated with apixaban and to 332 patients (57.3%) treated with dalteparin. In patients treated with apixaban, recurrent VTE occurred in 20 (6.0%) and 12 (5.0%) among patients treated or not treated with anticancer agents, respectively (hazard ratio [HR] = 1.14; 0.55-2.38); major bleeding occurred in 12 (3.6%) and 10 (4.2%) patients , respectively (HR = 0.79; 0.34-1.82), and death occurred in 74 (22.0%) and 61 (25.4%) patients , respectively (HR = 0.71; 0.51-1.00). In patients treated with dalteparin, recurrent VTE occurred in 24 (7.2%) and 22 (8.9%) among patients treated or not treated with anticancer agents, respectively (HR = 0.71; 0.40-1.28); major bleeding occurred in 16 (4.8%) and 7 (2.8%) patients, respectively (HR = 1.78; 0.66-4.79), and death occurred in 87 (26.2%) and 66 (26.7%) patients, respectively (HR = 0.85; 0.62-1.18). The comparative efficacy and safety of apixaban and dalteparin was not different in patients treated or not treated with anticancer agents. No effect on recurrent VTE, major bleeding or death was observed with inhibitors or inducers of P-glycoprotein and/or CYP3A4.

Conclusion: In our study, concomitant administration of anticancer agents had no effect on the risk of VTE recurrence or major bleeding in patients treated with apixaban or dalteparin for cancer-associated VTE.
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http://dx.doi.org/10.1016/j.ejca.2021.02.026DOI Listing
May 2021

Non-invasive early exclusion of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the InShape II study.

Thorax 2021 Oct 23;76(10):1002-1009. Epub 2021 Mar 23.

Department of Thrombosis and Hemostasis, Leiden Universitair Medisch Centrum, Leiden, The Netherlands

Background: The current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies for early CTEPH diagnosis are lacking. Echocardiographic screening among all PE survivors is associated with overdiagnosis and cost-ineffectiveness. We aimed to validate a simple screening strategy for excluding CTEPH early after acute PE, limiting the number of performed echocardiograms.

Methods: In this prospective, international, multicentre management study, consecutive patients were managed according to a screening algorithm starting 3 months after acute PE to determine whether echocardiographic evaluation of pulmonary hypertension (PH) was indicated. If the 'CTEPH prediction score' indicated high pretest probability or matching symptoms were present, the 'CTEPH rule-out criteria' were applied, consisting of ECG reading and N-terminalpro-brain natriuretic peptide. Only if these results could not rule out possible PH, the patients were referred for echocardiography.

Results: 424 patients were included. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During 2-year follow-up, one patient in whom echocardiography was deemed unnecessary by the algorithm was diagnosed with CTEPH, reflecting an algorithm failure rate of 0.29% (95% CI 0% to 1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients were diagnosed within 4 months after the PE presentation.

Conclusions: The InShape II algorithm accurately excluded CTEPH, without the need for echocardiography in the overall majority of patients. CTEPH was identified early after acute PE, resulting in a substantially shorter diagnostic delay than in current practice.
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http://dx.doi.org/10.1136/thoraxjnl-2020-216324DOI Listing
October 2021

Cost-effectiveness of magnetic resonance imaging for diagnosing recurrent ipsilateral deep vein thrombosis.

Blood Adv 2021 03;5(5):1369-1378

Department of Thrombosis and Hemostasis and.

The diagnostic workup of recurrent ipsilateral deep vein thrombosis (DVT) using compression ultrasonography (CUS) can be complicated by persistent intravascular abnormalities after a previous DVT. We showed that magnetic resonance direct thrombus imaging (MRDTI) can exclude recurrent ipsilateral DVT. However, it is unknown whether the application of MRDTI in daily clinical practice is cost effective. The aim of this study was to evaluate the cost effectiveness of MRDTI-based diagnosis for suspected recurrent ipsilateral DVT during first year of treatment and follow-up in the Dutch health care setting. Patient-level data of the Theia study (NCT02262052) were analyzed in 10 diagnostic scenarios, including a clinical decision rule and D-dimer test and imaging with CUS and/or MRDTI. The total costs of diagnostic tests and treatment during 1-year follow-up, including costs of false-positive and false-negative diagnoses, were compared and related to the associated mortality. The 1-year health care costs with MRDTI (range, €1219-1296) were generally lower than strategies without MRDTI (range, €1278-1529). This was because of superior specificity, despite higher initial diagnostic costs. Diagnostic strategies including CUS alone and CUS followed by MRDTI in case of an inconclusive CUS were potential optimal cost-effective strategies, with estimated average costs of €1529 and €1263 per patient and predicted mortality of 1 per 737 patients and 1 per 609 patients, respectively. Our model shows that diagnostic strategies with MRDTI for suspected recurrent ipsilateral DVT have generally lower 1-year health care costs than strategies without MRDTI. Therefore, compared with CUS alone, applying MRDTI did not increase health care costs.
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http://dx.doi.org/10.1182/bloodadvances.2020003849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948280PMC
March 2021

Diagnostic accuracy of four different D-dimer assays: A post-hoc analysis of the YEARS study.

Thromb Res 2021 05 6;201:18-22. Epub 2021 Feb 6.

Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Internal Medicine & Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands.

Introduction: For exclusion of pulmonary embolism (PE) clinical decision rules in combination with a D-dimer assay are applied. Currently available D-dimer assays are not standardized and it is unknown whether these differences have an impact on diagnostic management of suspected PE. Therefore, the aim is to explore differences between D-dimer assays and their impact on diagnostic outcome.

Methods: Data from all patients included in the YEARS study were collected. The YEARS study is a prospective, multicentre, cohort outcome study evaluating 3462 patients with suspected PE in which four different D-dimer assays were applied (Liatest, Innovance, Tinaquant, Vidas). Median D-dimer concentrations were calculated for each D-dimer assay. Sensitivity, specificity, PPV and NPV for detection of PE of all four assays were determined in patients without YEARS items and in those with ≥1 YEARS items (i.e. symptomatic deep vein thrombosis, haemoptysis, and whether PE is the most likely diagnosis).

Results: A total of 1323, 1100, 768 and 271 D-dimer concentrations were collected using the Liatest Innovance, Tinaquant and Vidas assay, respectively. Median D-dimer concentrations differed significantly between assays, with lowest values in the Tinaquant assay. In patients without YEARS items using a cutoff level of 1000 ng/mL, the NPV varied from 99,5 to 100%. In patients with ≥1 YEARS items using a 500 ng/mL cutoff, the NPV varied from 97,0 to 100% depending on the assay.

Conclusions: The overall high NPV for all assays demonstrates the clinical value of the D-dimer assay. However, these results confirm differences between D-dimer assays, which have an impact on follow-up imaging. This emphasizes the need for standardization of D-dimer assays.
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http://dx.doi.org/10.1016/j.thromres.2021.02.003DOI Listing
May 2021

Computed Tomography Pulmonary Perfusion for Prediction of Short-Term Clinical Outcome in Acute Pulmonary Embolism.

TH Open 2021 Jan 10;5(1):e66-e72. Epub 2021 Feb 10.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.

 Computed tomography pulmonary angiography (CTPA) is the imaging modality of choice for the diagnosis of acute pulmonary embolism (PE). With computed tomography pulmonary perfusion (CTPP) additional information on lung perfusion can be assessed, but its value in PE risk stratification is unknown. We aimed to evaluate the correlation between CTPP-assessed perfusion defect score (PDS) and clinical presentation and its predictive value for adverse short-term outcome of acute PE.  This was an exploratory, observational study in 100 hemodynamically stable patients with CTPA-confirmed acute PE in whom CTPP was performed as part of routine clinical practice. We calculated the difference between the mean PDS in patients with versus without chest pain, dyspnea, and hemoptysis and 7-day adverse outcome. Multivariable logistic regression analysis and likelihood-ratio test were used to assess the added predictive value of PDS to CTPA parameters of right ventricle dysfunction and total thrombus load, for intensive care unit admission, reperfusion therapy and PE-related death.  We found no correlation between PDS and clinical symptoms. PDS was correlated to reperfusion therapy (  = 4 with 16% higher PDS, 95% confidence interval [CI]: 3.5-28%) and PE-related mortality (  = 2 with 22% higher PDS, 95% CI: 4.9-38). Moreover, PDS had an added predictive value to CTPA assessment for PE-related mortality (from Chi-square 14 to 19,  = 0.02).  CTPP-assessed PDS was not correlated to clinical presentation of acute PE. However, PDS was correlated to reperfusion therapy and PE-related mortality and had an added predictive value to CTPA-reading for PE-related mortality; this added value needs to be demonstrated in larger studies.
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http://dx.doi.org/10.1055/s-0041-1723782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875679PMC
January 2021

Anticoagulation Prescription and Outcomes in Relation to Renal Function in Patients with Atrial Fibrillation: Results from GLORIA-AF.

TH Open 2021 Jan 6;5(1):e35-e42. Epub 2021 Feb 6.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.

 Anticoagulation management in patients with atrial fibrillation (AF) and impaired renal function is challenging. This study aimed to evaluate anticoagulation prescription patterns in relation to renal function and to describe 2-year clinical outcomes among dabigatran users.  Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is an international, prospective, and observational study program involving patients with newly diagnosed AF at risk for stroke. Prescription patterns were assessed by creatinine clearance (CrCl) at enrollment. Dabigatran users were followed for 2 years. Clinical outcomes were standardized for stroke and bleeding risk, based on CHA DS -VASc and HAS-BLED scores, with missing values imputed.  Baseline CrCl values were available for 12,056 of 15,308 eligible patients (79%). With declining renal function, prescriptions increased for vitamin K antagonists (VKAs) and decreased for dabigatran (30-47% and 34-12%, respectively). The prescription of other non-vitamin K antagonists remained similar across CrCl groups (14-19%). In 4,873 dabigatran users, standardized stroke rates were low across all CrCl groups; 0.58/100 patient-years (95% confidence interval [CI]: 0.30-0.90) in CrCl ≥80 mL/min, 0.85 (95% CI: 0.48-1.21) in CrCl 50 to 79 mL/min, and 0.33 (95% CI: 0.06-1.11) in CrCl 30 to 49 mL/min. Similarly, major bleeding rates were low and numerically increased with declining renal function (0.68/100 patient-years, 95% CI: 0.39-1.03; 0.92, 95% CI: 0.58-1.32; and 1.26, 95% CI: 0.66-1.97, respectively).  In patients with AF, VKA prescriptions increased and dabigatran prescriptions decreased with declining renal function. Rates of stroke and major bleeding in dabigatran patients remained low across the categories of renal impairment.
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http://dx.doi.org/10.1055/s-0040-1722706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867412PMC
January 2021
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