TH open : companion journal to thrombosis and haemostasis最新文献

Patients at extremes of body weight are underrepresented in randomized controlled trials of direct-acting oral anticoagulants (DOACs). Therefore, their optimal anticoagulant treatment remains a topic of debate. The aim of this narrative review is to summarize the evidence on the pharmacokinetic and pharmacodynamic profile of DOACs for treating patients at extremes of body weight in venous thromboembolism (VTE) and in the prevention of cardioembolic stroke in nonvalvular atrial fibrillation (NVAF). A literature search was conducted in the main bibliographic databases, and the most relevant reviews and original articles on the topic were selected. Although data in these patient groups are limited, apixaban and rivaroxaban show a favorable pharmacokinetic and pharmacodynamic profile in obese VTE treatment and NVAF patients and, in the case of apixaban, also in underweight patients. In particular, these drugs demonstrated comparable efficacy and safety to standard therapy. Very few data were available for dabigatran and edoxaban; the latter drug was safer at a lower dose, mainly in underweight patients. Our findings are in line with the last International Society of Haemostasis and Thrombosis position paper and European Heart Rhythm Association 2021 practical guide, suggesting the use of apixaban and rivaroxaban in morbidly obese patients (>120 kg or body mass index ≥40 kg/m ² ) and the reduced dosage of edoxaban in low-weight patients. Future studies should focus on large populations of patients at extremes of body weights to acquire more clinical and pharmacokinetic evidence on all available DOACs, especially those currently less investigated.

Background  In acute pulmonary embolism (PE), echocardiographic identification of right ventricular (RV) dysfunction will inform prognostication and clinical decision-making. Registro Informatizado Enfermedad TromboEmbolica (RIETE) is the world's largest registry of patients with objectively confirmed PE. The reliability of site-reported RV echocardiographic measurements is unknown. We aimed to validate site-reported key RV echocardiographic measurements in the RIETE registry. Methods  Fifty-one randomly chosen patients in RIETE who had transthoracic echocardiogram (TTE) performed for acute PE were included. TTEs were de-identified and analyzed by a core laboratory of two independent observers blinded to site-reported data. To investigate reliability, intraclass correlation coefficients (ICCs) and Bland-Altman plots between the two observers, and between an average of the two observers and the RIETE site-reported data were obtained. Results  Core laboratory interobserver variations were very limited with correlation coefficients >0.8 for all TTE parameters. Agreement was substantial between core laboratory observers and site-reported data for key parameters including tricuspid annular plane systolic excursion (ICC 0.728; 95% confidence interval [CI], 0.594-0.862) and pulmonary arterial systolic pressure (ICC 0.726; 95% CI, 0.601-0.852). Agreement on right-to-left ventricular diameter ratio (ICC 0.739; 95% CI, 0.443-1.000) was validated, although missing data limited the precision of the estimates. Bland-Altman plots showed differences close to zero. Conclusion  We showed substantial reliability of key RV site-reported measurements in the RIETE registry. Ascertaining the validity of such data adds confidence and reliability for subsequent investigations.

Introduction  Atrial fibrillation (AF) increases the risk of ischemic stroke (IS). We hypothesized that the functional form of platelet receptor glycoprotein (GP) VI, GPVI-dimer, which binds to collagen and fibrin causing platelet activation, is overexpressed in patients with AF who have not had a stroke. Methods  A total of 75 inpatients with AF were recruited. None were admitted with or had previously had thrombotic events, including IS or myocardial infarction. Platelet surface expression of total GPVI, GPVI-dimer, and the platelet activation marker P-selectin were quantitated by whole blood flow cytometry. Serum biomarkers were collected in AF patients. Results were compared against patients contemporaneously admitted to hospital with similar age and vascular risk-factor profiles without AF (noAF, n  = 30). Results  Patients with AF have similar total GPVI surface expression ( p  = 0.58) and P-selectin exposure ( p  = 0.73) on their platelets compared with noAF patients but demonstrate significantly higher GPVI-dimer expression ( p  = 0.02 ). Patients with paroxysmal AF express similar GPVI-dimer levels compared with permanent AF and GPVI-dimer levels were not different between anticoagulated groups. Serum N-terminal pro b-type natriuretic peptide ( p  < 0.0001 ) and high sensitivity C-reactive protein ( p  < 0.0001 ) were significantly correlated with GPVI-dimer expression in AF platelets. AF was the only vascular risk factor that was independently associated with higher GPVI-dimer expression in the whole population ( p  = 0.02 ) . Conclusion  GPVI inhibition is being explored in clinical trials as a novel target for IS treatment. As GPVI-dimer is elevated in AF patients' platelets, the exploration of targeted GPVI-dimer inhibition for stroke prevention in patients at high risk of IS due to AF is supported.

Background  For most patients with newly diagnosed atrial fibrillation (AF), direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists. However, there is concern that the lack of monitoring may impair therapy adherence and therefore the anticoagulant effect. Objective  To assess 1-year DOAC nonadherence in patients with AF and a treatment indication of at least 1 year in the Dutch health care setting, and to identify predictors of nonadherence. Methods  We performed a near-nationwide historical cohort study in patients with a novel DOAC indication for AF. Data were obtained from a pharmacy database, covering 65% of all outpatient prescriptions dispensed in the Netherlands. The 1-year nonadherence was assessed by the proportion of days covered; the threshold was set at <80%. Robust Poisson regression analyses were performed to identify predictors of nonadherence. Results  A total of 46,211 patients were included and the 1-year nonadherence was 6.5%. We identified male sex (risk ratio [RR] 1.23, 95% confidence interval [CI]: 1.15-1.33), younger age (age ≥60 to <70 years: RR: 1.15, 95% CI: 1.00-1.33, age <60 years: RR: 2.22, 95% CI: 1.92-2.57; reference age ≥85 years), a reduced DOAC dose (RR: 1.10, 95% CI: 1.00-1.22), a twice-daily dosing regimen (RR: 1.21, 95% CI: 1.12-1.30), and treatment with apixaban (RR: 1.16, 95% CI: 1.06-1.26, reference rivaroxaban) or dabigatran (RR: 1.25, 95% CI: 1.14-1.37) as independent predictors of 1-year nonadherence. Conclusion  One-year nonadherence to DOACs was low yet relevant in patients with AF newly prescribed a DOAC. Understanding the predictors for nonadherence may help identify patients at risk.