Low-molecular-weight heparins in the treatment of venous thromboembolism

Venous thromboembolism is a common disease that is associated with considerable morbidity if left untreated. Recently, low-molecular-weight heparins (LMWHs) have been evaluated for use in acute treatment of deep venous thrombosis and pulmonary embolism. Randomized studies have shown that LMWHs are as effective as unfractionated heparin in the prevention of recurrent venous thromboembolism, and are as safe with respect to the occurrence of major bleeding. A pooled analysis did not show substantial differences among different LMWH compounds used, but no direct comparison of the different LMWHs is currently available. Finally, in patients with pulmonary embolism, there is a relative lack of large studies of daily practice. It could be argued that large prospective studies, in patients who were treated with LMWHs from the moment of diagnosis, are needed

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

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

Pulmonary flow profile and distensibility following acute pulmonary embolism

<p>Abstract</p> <p>Objective</p> <p>Proof of concept study evaluating CMR as screening tool for chronic thromboembolic pulmonary hypertension (CTEPH) in patients treated for acute pulmonary embolism (PE).</p> <p>Materials and methods</p> <p>Right and left ventricular function of 15 consecutive patients treated for PE and 10 consecutive patients in whom PE was excluded was estimated at baseline by cardiac CT and at 6 months follow-up by CMR. Additionally, during the follow-up visit, pulmonary artery (PA) hemodynamics were studied by CMR and the presence of pulmonary hypertension by echocardiography.</p> <p>Results</p> <p>CT measured right ventricular ejection fraction (RVEF) was lower in patients with PE compared to patients without PE at time of diagnosis (median 47%, interquartile range 39-53 vs. 55%, 52-58; p = 0.014). After 6 months follow up, the RVEF between patients treated for PE and patients without PE were not statistically significant different (55%, 52-60 versus 54%, 51-57; p = 0.57), as were distensibility index (0.18 ± 0.18 versus 0.25 ± 0.18, p = 0.20), mean velocity (14.1 ± 3.9 cm/s versus 14.0 ± 2.5 cm/s, p = 0.81), peak velocity (86.5 ± 22 cm/s versus 89.6 ± 13 cm/s, p = 0.43) and time to peak PA blood flow velocity (142 ± 49 ms versus 161 ± 29 ms, p = 0.14). One patient was diagnosed with CTEPH and CMR revealed poor right systolic function, decreased PA distensibility and flow velocity, and a systolic notch in the PA flow profile consistent with persistent PA obstruction.</p> <p>Conclusion</p> <p>In this small series, right ventricular performance and PA flow profiles of patients treated for 6 months after PE are equivalent to those parameters in normal patients.</p

The rationale, design, and methods of a randomized, controlled trial to evaluate the efficacy and safety of an active strategy for the diagnosis and treatment of acute pulmonary embolism during exacerbations of chronic obstructive pulmonary disease.

Introduction: Some previous studies have suggested a high prevalence of pulmonary embolism (PE) during exacerbations of chronic obstructive pulmonary disease (ECOPD). The SLICE trial aims to assess the efficacy and safety of an active strategy for the diagnosis and treatment of PE (vs usual care) in patients hospitalized because of ECOPD. Methods: SLICE is a phase III, prospective, international, multicenter, randomized, open-label, and parallel-group trial. A total of 746 patients hospitalized because of ECOPD will be random- ized in a 1:1 fashion to receive either an active strategy for the diagnosis and anticoagulant treatment of PE or usual care (ie, standard care without any diagnostic test for diagnosing PE). The primary outcome is a composite of all-cause death, non-fatal (recurrent) venous thrombo- embolism (VTE), or readmission for ECOPD within 90 days after enrollment. Secondary out- comes are (a) death from any cause within 90 days after enrollment, (b) non-fatal (recurrent) VTE within 90 days after enrollment, (c) readmission within 90 days after enrollment, and (d) length of hospital stay. Results: Enrollment started in September 2014 and is expected to proceed until 2020. Median age of the first 443 patients was 71 years (interquartile range, 64-78), and 26% were female. Conclusions: This multicenter trial will determine the value of detecting PEs in patients with ECOPD. This has implications for COPD patient morbidity and mortality.Ministerio de Salud, Instituto de Salud Carlos III: PI14/0040

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation: The GLORIA-AF registry

Aim The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial

Adherence to the Atrial Fibrillation Better Care (ABC) pathway and the risk of major outcomes in patients with atrial fibrillation:A post-hoc analysis from the prospective GLORIA-AF Registry

BackgroundThe 'Atrial fibrillation Better Care' (ABC) pathway has been proposed to streamline a more holistic or integrated care approach to atrial fibrillation (AF) management. We aimed to analyse the impact of adherence to the ABC pathway on the risk of major adverse outcomes in a contemporary prospective global cohort of patients with AF.MethodsPatients enrolled Phase II and III of the GLORIA-AF Registry with complete data on ABC pathway adherence and follow-up were included in this post-hoc analysis between November 2011 and December 2014 for Phase II, and between January 2014 and December 2016 for Phase III. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Multivariable Cox-regression and delay of event (DoE) analyses were used to evaluate the association between adherence to the ABC pathway and the risk of outcomes.FindingsWe included 24,608 patients in this analysis (mean age: 70.2 (10.3) years, 10,938 (44.4%) females). Adherence to the ABC pathway was associated with a significant risk reduction for the primary outcome, with greatest magnitude observed for full ABC pathway adherence (adjusted Hazard Ratio [aHR] 0.54, 95% Confidence Interval [CI]: 0.44-0.67, p InterpretationAdherence to the ABC pathway in patients with AF was associated with a reduced risk of major adverse events, including mortality, thromboembolism and MACE. This underlines the importance of using the ABC pathway in the clinical care of patients with AF.FundingThis study was funded by Boehringer Ingelheim

Correction:Cost-effectiveness of apixaban compared to other anticoagulants in patients with atrial fibrillation in the real-world and trial settings

[This corrects the article DOI: 10.1371/journal.pone.0222658.]

Real world time trends in antithrombotic treatment for newly diagnosed atrial fibrillation in China: reports from the GLORIA-AF Phase III registry : Trends in antithrombotic therapy use in China.

BackgroundStroke prevention with oral anticoagulant (OAC) therapy, including non-vitamin K antagonist oral anticoagulants (NOACs), is recommended in patients with atrial fibrillation (AF). This analysis describes the antithrombotic prescription patterns for Chinese patients enrolled post-dabigatran approval during Phase II and III of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) program in China.MethodsPatients aged ≥ 18 years with newly diagnosed (2DS2-VASc score ≥ 1) were consecutively enrolled in the GLORIA-AF registry. This cross-sectional analysis provides descriptive comparison of Chinese patients in Phase III (2015-2016) with those enrolled in Phase II (2013-2014).ResultsOverall, 1,018 and 1,911 Chinese patients were eligible for analysis in Phase II and III, respectively. Most patients (69.6% and 69.1%, respectively) had high stroke risk (CHA2DS2-VASc score ≥ 2 for males and ≥ 3 for females). High bleeding risk (HAS-BLED score ≥ 3) rates were similar (17.3% for Phase II, 17.6% for Phase III). In Phase II, 5.8%, 15.2%, 36.7% and 42.2% of patients were prescribed NOACs, vitamin K antagonists (VKAs), antiplatelet therapies or no antithrombotic treatment, respectively. The corresponding figures were 17.2%, 23.5%, 37.4% and 21.8% for patients in Phase III, with an overall increase in OAC prescriptions (NOACs or VKAs). In patients with high stroke risk, the prescription patterns in Phase II were 5.6%, 14.4%, 41.0% and 38.9% for NOACs, VKAs, antiplatelets or no antithrombotic treatment, respectively. The respective proportions in Phase III were 15.1%, 23.5%, 40.9% and 20.5%.ConclusionsSince the availability of dabigatran in China, the overall trend of OAC, including NOAC, prescriptions in Chinese patients with nonvalvular AF has increased over time, albeit with VKAs as the most common antithrombotic treatment. Most patients, including those at high stroke risk, remain undertreated according to best practice guidelines.Trial registrationClinicalTrials.gov NCT01468701