We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce ...Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor‐1 (PAI‐1) and thrombin‐activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non‐rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8·75 min (95% CI −13·8 to −3·72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (−0·05 U/ml; 95% CI −0·07 to −0·02 and −4·77%; 95% CI −6·81 to −2·73, respectively). PAI‐1 levels did not change and fibrinogen levels were 0·17 g/l (95% CI 0·04–0·29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non‐statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE.
Background
Non‐valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low.
...Objective
To examine if pre‐switch TTR determines persistence patterns in NVAF patients who are switched from a VKA to DOAC.
Patients/Methods
Adult NVAF patients from three Dutch anticoagulation clinics who were newly switched from a VKA to DOAC between July 1, 2013 and September 30, 2018 were stratified by pre‐switch TTR levels. DOAC prescription records were examined to determine persistence patterns according to a 100‐day prescription gap. Cumulative incidences of non‐persistence to DOAC were estimated using the cumulative incidence competing risk method. The association of pre‐switch TTR levels with DOAC non‐persistence was evaluated by Cox regression models.
Results
A total of 3696 NVAF patients were included, of whom 690 (18.7%) had a pre‐switch TTR ≤ 45%. After switching from VKA to DOAC, 14.0% (95% confidence interval CI 11.3–17.0%) of the patients with a pre‐switch TTR ≤ 45% became non‐persistent to DOAC within 1 year, while 9.8% (95% CI 8.7–11.0%) did in those with a pre‐switch TTR > 45%. In a multivariable model, a pre‐switch TTR ≤ 45% was associated with a higher risk of non‐persistence to DOAC (adjusted hazard ratio 1.55, 95% CI 1.22–1.97). Results were similar when using other cut‐off points (60% or 70%) to define a low TTR.
Conclusion
NVAF patients switching from VKA to DOAC due to a low pre‐switch TTR saw a worse persistence pattern to DOAC after the switch compared to patients with a high pre‐switch TTR.
Objectives Chromogenic anti-activated factor X (FXa) assays are currently the "gold standard" for monitoring indirect anticoagulants. However, anti-FXa has been shown to vary according to the choice ...of reagents. In the present study, the performance of anti-FXa measurement was evaluated in order to gain more insight into the clinical applications. Furthermore, the longitudinal coefficient of variation (CV) was studied to investigate whether there is improvement over time. Methods Laboratory tests results were evaluated for samples spiked with unfractionated heparin (UFH), low-molecular-weight-heparin (LMWH), fondaparinux and danaparoid sodium. External quality assessment (EQA) data from multiple years were used from more than 100 laboratories. Results Comparison of the results for all methods showed significant differences in measured values between the frequently used methods (ANOVA: p < 0.001). The largest differences were observed for LMWH and UFH measurements. These differences may be caused by differences in method composition, such as the addition of dextran sulphate. Substantial interlaboratory variation in anti-FXa monitoring was observed for all parameters, particularly at low concentrations. Our results showed that below 0.35 IU/mL, the CVs for UFH and LMWH increase dramatically and results below this limit should be used with caution. Conclusions Our study demonstrates that the choice of the anti-FXa method is particularly important for UFH and LMWH measurement. The variation in measurements may have an effect on clinical implications, such as therapeutic ranges. Furthermore, the longitudinal EQA data demonstrated a constant performance and, in at least 50% of the cases, improvement in the CV% of the anti-Xa results over time.
Background
Since direct oral anticoagulants (DOACs) have been introduced for treatment and prevention of thromboembolic diseases, patients on vitamin K antagonists (VKA) have to decide whether to ...remain on VKA or switch to DOAC. The goal of this study was to evaluate treatment satisfaction, preferences, and concerns among those who already have switched from VKA to DOAC.
Methods
A questionnaire was sent to 2920 former patients of three anticoagulation clinics in the Netherlands, who switched from VKA to DOAC (2016‐2017). Questions concerned demographics, treatment satisfaction, concerns, perspectives on antidotes, and monitoring. To identify predictors for being concerned about adverse events, logistic regression was used to estimate crude‐ and adjusted (age and sex) odds ratios (OR) and 95% confidence intervals (95% CI).
Results
One thousand, three hundred ninety‐nine questionnaires (response rate 48%) were used for analysis. DOAC treatment satisfaction was high (mean 8.8 of a maximum 10‐point score). A quarter of patients expressed concerns about adverse events. Predictors for being concerned were age < 60 years (vs age > 75 years, OR 4.1, 95% CI 2.6‐6.4), female sex (OR 1.3, 95% CI 1.0‐1.6), and high education (OR 1.6, 95% CI 1.2‐2.2). Fifty‐nine percent of all patients indicated antidote availability as important, 73% would be willing to participate in DOAC monitoring.
Conclusions
DOAC treatment satisfaction was high. A substantial number of patients expressed concerns about adverse events, especially women, patients aged < 60 years, or highly educated patients. Our findings among patients who already had switched to DOAC may assist in the process of shared decision‐making when switching a patient from VKA to DOAC is considered.
Background In the Netherlands, each new lot of test strips for the CoaguChek XS is validated by a group of collaborating centers. The purpose of this study was to assess the accuracy of the ...international normalized ratio (INR) measured with consecutive test strip lots and the suitability of frozen plasma pools for accuracy evaluation. Methods Each year, a particular lot of CoaguChek XS test strips is used as reference lot. The reference lots have been validated with the International Standard for thromboplastin rTF/09, yielding a mathematical relationship (R1) between reference lot INR and International Standard INR. New lots are compared to the reference lot using patients' capillary blood samples, yielding a relationship (R2) between the new lot INR and the reference lot INR. INRs of the blood samples were within the 1.5-4.5 interval. In parallel, three frozen plasmas pools are analyzed with the test strips. The distance of each plasma point to the line of relationship R2 was assessed. Results Fifty-four test strip lots have been evaluated during 3 years (2014-2016). Mean INR differences between test strip lot and International Standard rTF/09 varied between -0.14 and +0.20 (-4% and +8%, respectively). A positive trend with strip lot sequence number was observed (p<0.001). In several cases, the distance of the frozen plasmas to the whole blood relationship (R2) was greater than the critical value for commutability. Conclusions Using whole blood, all evaluated test strip lots met the analytical bias criterion of ±10%. Frozen plasma pools behave differently compared to whole blood and are not suitable for assessing absolute accuracy of new CoaguChek XS test strips.
Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new ...biomarkers that predict bleeding in these patients.
To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations.
A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR.
Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations.
BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality, with immunocompromised patients (ICPs) at particular risk. Therefore, guidelines recommend pneumococcal ...vaccination for these patients. However, guidelines are scarcely underpinned with references to incidence studies of IPD in this population. This, potentially results in unawareness of the importance of vaccination and low vaccination rates. The objective of this systematic review and meta-analysis was to assess the incidence of IPD in ICPs.
We systematically searched PubMed and Embase to identify studies in English published before December 6th, 2017 that included terms related to ‘incidence’, ‘rate’, ‘pneumococcal’, ‘pneumoniae’, ‘meningitis’, ‘septicemia’, or ‘bacteremia’. We focused on patients with HIV, transplantation and chronic inflammatory diseases.
We included 45 studies in the systematic review reporting an incidence or rate of IPD, defined as isolation of Streptococcus pneumoniae from a normally sterile site. Random effects meta-analysis of 38 studies showed a pooled IPD incidence of 331/100,000 person years in patients with HIV in the late-antiretroviral treatment era in non-African countries, and 318/100,000 in African countries; 696 and 812/100,000 in patients who underwent an autologous or allogeneic stem cell transplantation, respectively; 465/100,000 in patients with a solid organ transplantation; and 65/100,000 in patients with chronic inflammatory diseases. In healthy control cohorts, the pooled incidence was 10/100,000.
ICPs are at increased risk of contracting IPD, especially those with HIV, and those who underwent transplantation. Based on our findings, we recommend pneumococcal vaccination in immunocompromised patients.
ID: CRD42016048438.
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.
Background
A high number of vitamin K antagonist (VKA) users have a low proportion of time in therapeutic range (TTR) resulting in a high number of bleeding and thromboembolism events.
Objective
Can ...the quality of anticoagulation be improved by dispensing VKAs via multidose drug dispensing (MDD).
Method
A randomized controlled trial in the Netherlands. Patients who used VKAs, ≥65 years of age with a TTR <65% were eligible for inclusion. All oral drugs were dispensed via MDD. In MDD systems, all oral chronic medication intended for one dosing moment is packed in plastic disposable pouches. Controls received VKAs by manual dispensing. The difference in TTR between the 6 months after‐ and 6 months before the index date. A mixed‐effects model with the intervention, TTR before the index date, MDD system at baseline as covariates, and pharmacy as random effect. A per‐protocol analysis was performed with all patients who completed the study as intended.
Results
One hundred and seventy‐nine patients were included. Mean age was 80.0 (SD 6.9) years. Mean TTR during the study was 79.2 ± 18.0% in the intervention group and 72.5 ± 20.1% in the control group. The intervention resulted in a 5.6% (95% CI: 0.1‐11.1) increase in TTR compared to the control group. Per‐protocol analysis resulted in an 8.3% (95% CI: 0.99‐15.61) increase in TTR compared to the control group. No differences in reduction were observed between the intervention and control group.
Conclusion
The quality of anticoagulation can be improved with the use of MDD systems.
To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm.
Pediatric patients who used phenprocoumon were ...invited to participate in a retrospective follow-up study. Clinical information and genotypes of genetic variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and tested with linear regression for association with phenprocoumon dose requirement.
Of the 41 patients included in the analysis, age, VKORC1, CYP2C9*2/*3 and CYP3A4*1B were statistically significantly associated with dose requirement, and together explained 80.4% of the variability in phenprocoumon dose requirement.
Our study reveals that age and genetic variations explain a significant part of the variability in phenprocoumon dose requirement in pediatric patients.
PDF
