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Contains fulltext : 305934.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 292744.pdf (Publisher’s version ) (Open Access), OBJECTIVE: Postmarketing observational studies report that a substantial percentage of patients with atrial fibrillation (AF) receive a reduced non-vitamin K antagonist oral anticoagulant (NOAC) dose without a clear indication. Recently, increasing evidence has become available to explore the clinical consequences of such off-label reduced dosing (OLRD). This study aims to systematically review and meta-analyse observational studies that report clinical outcomes associated with OLRD of NOACs compared with on-label non-reduced dosing (OLNRD) of NOACs in patients with AF. METHODS AND ANALYSIS: We performed a systematic literature review and meta-analysis of observational studies reporting clinical outcomes in AF patients with OLRD of an NOAC compared with AF patients with OLNRD of an NOAC. Using random effects meta-analyses, we estimated the risk of stroke/thromboembolism, bleeding and all-cause mortality. RESULTS: We included 19 studies with a total of 170 394 NOAC users. In these studies, the percentage of OLRD among patients with an indication for an on-label non-reduced NOAC dose ranged between 9% and 53%. 7 of these 19 studies met the predefined criteria for meta-analysis (n=80 725 patients). The pooled HR associated with OLRD of NOACs was 1.04 (95% CI 0.83 to 1.29; 95% prediction interval (PI) 0.60 to 1.79) for stroke/thromboembolism, 1.10 (95% CI 0.95 to 1.29; 95% PI 0.81 to 1.50) for bleeding and 1.22 (95% CI 0.81 to 1.84; 95% PI 0.55 to 2.70) for all-cause mortality. CONCLUSION: This meta-analysis shows no statistically significant increased risk of stroke/thromboembolism, nor a decreased bleeding risk, nor a difference in risk of all-cause mortality in patients with OLRD of NOACs. Future research may focus on differences between NOACs.

Item does not contain fulltext, IMPORTANCE: Cardiac implantable electronic device (CIED) infection is a potentially devastating complication with an estimated 12-month mortality of 15% to 30%. The association of the extent (localized or systemic) and timing of infection with all-cause mortality has not been established. OBJECTIVE: To evaluate the association of the extent and timing of CIED infection with all-cause mortality. DESIGN, SETTING, AND PARTICIPANTS: This prospective observational cohort study was conducted between December 1, 2012, and September 30, 2016, in 28 centers across Canada and the Netherlands. The study included 19 559 patients undergoing CIED procedures, 177 of whom developed an infection. Data were analyzed from April 5, 2021, to January 14, 2023. EXPOSURES: Prospectively identified CIED infections. MAIN OUTCOMES AND MEASURES: Time-dependent analysis of the timing (early [≤3 months] or delayed [3-12 months]) and extent (localized or systemic) of infection was performed to determine the risk of all-cause mortality associated with CIED infections. RESULTS: Of 19 559 patients undergoing CIED procedures, 177 developed a CIED infection. The mean (SD) age was 68.7 (12.7) years, and 132 patients were male (74.6%). The cumulative incidence of infection was 0.6%, 0.7%, and 0.9% within 3, 6, and 12 months, respectively. Infection rates were highest in the first 3 months (0.21% per month), reducing significantly thereafter. Compared with patients who did not develop CIED infection, those with early localized infections were not at higher risk for all-cause mortality (no deaths at 30 days [0 of 74 patients]: adjusted hazard ratio [aHR], 0.64 [95% CI, 0.20-1.98]; P = .43). However, patients with early systemic and delayed localized infections had an approximately 3-fold increase in mortality (8.9% 30-day mortality [4 of 45 patients]: aHR, 2.88 [95% CI, 1.48-5.61]; P = .002; 8.8% 30-day mortality [3 of 34 patients]: aHR, 3.57 [95% CI, 1.33-9.57]; P = .01), increasing to a 9.3-fold risk of

Item does not contain fulltext, AIMS: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guidelines to prevent strokes. Cost-effectiveness analyses of different screening programmes for AF are difficult to compare because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programmes in the Netherlands. METHODS AND RESULTS: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY, and ROCKET AF trials combined with Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed. The maximum number of newly detected AF patients in the Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of >3000 strokes prevented using single-time point AF screening. Compared with no screening, screening 100 000 people provided a gain in QALYs ranging from 984 to 8727 and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. The probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥75 years visiting the geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥65 years visiting the GPs office had the highest impact on strokes prevented. CONCLUSION: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention.

01 april 2023, Item does not contain fulltext, OBJECTIVE: Patients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with cancer are lacking. The aim of this study is to predict bleeding risk in anticoagulated patients with cancer. METHODS: We performed a study using the routine healthcare database of the Julius General Practitioners' Network. Five bleeding risk models were selected for external validation. Patients with a new cancer episode during anticoagulant treatment or those initiating anticoagulation during active cancer were included. The outcome was the composite of major bleeding and clinically relevant non-major (CRNM) bleeding. Next, we internally validated an updated bleeding risk model accounting for the competing risk of death. RESULTS: The validation cohort consisted of 1304 patients with cancer, mean age 74.0±10.9 years, 52.2% males. In total 215 (16.5%) patients developed a first major or CRNM bleeding during a mean follow-up of 1.5 years (incidence rate; 11.0 per 100 person-years (95% CI 9.6 to 12.5)). The c-statistics of all selected bleeding risk models were low, around 0.56. Internal validation of an updated model accounting for death as competing risk showed a slightly improved c-statistic of 0.61 (95% CI 0.54 to 0.70). On updating, only age and a history of bleeding appeared to contribute to the prediction of bleeding risk. CONCLUSIONS: Existing bleeding risk models cannot accurately differentiate bleeding risk between patients. Future studies may use our updated model as a starting point for further development of bleeding risk models in patients with cancer.

Item does not contain fulltext, In patients with short episodes of clinical, non-triggered AF is the evidence for long-term anticoagulation based on the CHA2DS2-VASc score strong. In situations where a temporary trigger for AF is observed (e.g. after surgery or an infection), or when AF is only detected on a cardiac implantable electronic device (CIED) or smartwatch, the evidence for anticoagulation is less well established. Despite the short duration of the AF episode(s), both patients with subclinical or triggered AF are often at an inherently increased risk of stroke or thromboembolism. In some of these cases long-term anticoagulation can be considered, especially when other cardiovascular risk factors are present. Important considerations when deciding to start with long-term anticoagulation are the individually estimated risk of thrombosis and bleeding, the implementation of shared decision making, and the optimization of the overall cardiovascular risk management.

Contains fulltext : 296059.pdf (Publisher’s version ) (Open Access), OBJECTIVES: To investigate the underprescription of oral anticoagulation (OAC) in individual atrial fibrillation (AF) patients in primary care. SETTING: Screening of patient records in 39 participating general practitioners (GPs) across the Netherlands. PARTICIPANTS: We screened 101 207 patient records identifying 2375 non-valvular AF patients. METHODS: Using electronic patient files, we were able to screen the entire GP population for AF, CHA(2)DS(2)-VASc stroke risk scores, and the use of guidelines recommended OAC prescription. In case of a deviation from guidelines recommended OAC prescription, we checked the electronic patient file for any documented reason. Additionally, 6 weeks following the screening, we asked all GPs to provide information on any actions taken for the underprescribed patients. RESULTS: We found a mean CHA(2)DS(2)-VASc score of 3.2. OAC prescription consisted of direct OAC in 1342/1984 (68%) and vitamin K-antagonists in the remainder of patients. OAC underprescription was present in 93/944 (9.9%) females and 101/1374 (9.7%) in males, respectively. In 111/146 (76.0%) of the underprescribed AF patients, no reason to withhold OAC was reported. Reported reasons to withhold OAC were patient refusal (n=10), cardiologist advice (n=7) and high risk of bleeding (n=7). Data regarding actions following the identification of OAC underprescription were available for 92/194 (47%) of the OAC underprescribed cases. After consultation OAC was initiated in 9/92 (10%) only. CONCLUSIONS: In this large Dutch study among GPs, we observed 9.8% underprescription of OAC in AF patients. In 76% of the AF patients lacking a prescription for OAC, no documentation for deviating from the guidelines was found. Only in a minority of cases detection of OAC underprescription lead to OAC initiation.

Item does not contain fulltext, OBJECTIVE: Atrial fibrillation (AF) is associated with adverse events including conduction disturbances, ventricular arrhythmias and sudden death. The aim of this study was to examine brady- and tachyarrhythmias using continuous rhythm monitoring in patients with paroxysmal self-terminating AF (PAF). METHODS: In this multicentre observational substudy to the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V), we included 392 patients with PAF and at least 2 years of continuous rhythm monitoring. All patients received an implantable loop recorder, and all detected episodes of tachycardia ≥182 beats per minute (BPM), bradycardia ≤30 BPM or pauses ≥5 s were adjudicated by three physicians. RESULTS: Over 1272 patient-years of continuous rhythm monitoring, we adjudicated 1940 episodes in 175 patients (45%): 106 (27%) patients experienced rapid AF or atrial flutter (AFL), pauses ≥5 s or bradycardias ≤30 BPM occurred in 47 (12%) patients and in 22 (6%) patients, we observed both episode types. No sustained ventricular tachycardias occurred. In the multivariable analysis, age >70 years (HR 2.3, 95% CI 1.4 to 3.9), longer PR interval (HR 1.9, 1.1-3.1), CHA(2)DS(2)-VASc score ≥2 (HR 2.2, 1.1-4.5) and treatment with verapamil or diltiazem (HR 0.4, 0.2-1.0) were significantly associated with bradyarrhythmia episodes. Age >70 years was associated with lower rates of tachyarrhythmias. CONCLUSIONS: In a cohort exclusive to patients with PAF, almost half experienced severe bradyarrhythmias or AF/AFL with rapid ventricular rates. Our data highlight a higher than anticipated bradyarrhythmia risk in PAF. TRIAL REGISTRATION NUMBER: NCT02726698.

01 augustus 2023, Item does not contain fulltext

Contains fulltext : 294501.pdf (Publisher’s version ) (Open Access), BACKGROUND: Cancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF). OBJECTIVES: We aimed to describe current anticoagulant practice in patients with AF and active cancer, present incidences of thromboembolic and bleeding complications, and evaluate the association between cancer type or anticoagulant management strategy with AF-related complications. METHODS: This retrospective study identified patients with AF and active cancer in 2 hospitals between January 1, 2012, and December 31, 2017. Follow-up lasted for 2 years. Data on cancer and anticoagulant treatment were collected. The outcomes of interest included ischemic stroke or transient ischemic attack (TIA) and clinically relevant nonmajor bleeding (CRNMB/MB). Incidence rates (IRs) per 100 patient-years and subdistribution hazard ratios (SHRs) with corresponding 95% Cis were estimated. RESULTS: We identified 878 patients with AF who developed cancer (cohort 1) and 335 patients with cancer who developed AF (cohort 2). IRs for ischemic stroke/TIA and MB/CRNMB were 3.9 (2.8-5.3) and 15.7 (13.3-18.5) for cohort 1 and 4.0 (2.2-6.7) and 16.7 (12.6-21.7) for cohort 2. 14.2% (cohort 1) and 19.1% (cohort 2) of patients with a CHA(2)DS(2)-VASc score of ≥2 did not receive anticoagulant treatment. Withholding anticoagulants was associated with thromboembolic complications (SHR: 5.1 [3.20-8.0]). In nonanticoagulated patients with a CHA(2)DS(2)-VASc score of <2, IRs for stroke/TIA were 4.5 (0.75-15.0; cohort 1) and 16.0 (5.1-38.7; cohort 2). CONCLUSION: Patients with AF and active cancer experience high rates of thromboembolic and bleeding complications, underlying the complexity of anticoagulant management in these patients. Our data suggest that the presence of cancer is an important factor in determining the indication for anticoagulants in patients with a low CHA(2)DS(2)-VASc score.

Contains fulltext : 294758.pdf (Publisher’s version ) (Open Access), BACKGROUND: Major bleeding, and intracranial bleeding specifically, are severe complications related to the use of anticoagulation. To what extent the risk for major bleeding is elevated among frail older people is not well known because they are underrepresented in the randomized clinical trials (RCTs). This study investigates the risk for major bleeding (MB) and intra cranial haemorrhage (ICH) in frail older people who fall. METHODS: All patients 65 years and older visiting the Fall and Syncope Clinic, between November 2011 and January 2020, and underwent a MRI of the brain were eligible. Frailty was assessed with a Frailty Index, based on the accumulation of deficits model. Cerebral small vessel disease was described and evaluated as proposed in the position paper of Wardlaw and colleagues in 2013. RESULTS: 479 patients were included in this analysis. Mean follow-up was 7 years per patient (ranging from 1 month to 8 years and 5 months). 368 patients (77%) were frail. A total of 81 patients used oral anticoagulation (OAC). 17 extracranial MB of which 3 were traumatic and 14 gastrointestinal, and 16 ICH occurred. There was a total of 603.4 treatment years with OAC, and 8 MBs occurred among patients on OAC (bleeding rate 1.32 per 100 treatment years), of which 2 ICHs (bleeding rate 0.33 per 100 treatment years). The risk for extracranial MB was increased by the use of antiplatelet agents (APA) (adjusted OR 6.9, CI 95% 1.2-38.3), and by the use of OAC (adjusted OR 9.8, CI 95% 1.7-56.1). The risk for ICH was only heightened by white matter hyperintensities (WMH) (adjusted OR 3.8, CI 95% 1.0-13.4). The use of APA (adjusted OR 0.9, CI 95% 0.3-3.3) or OAC (adjusted OR 0.6, CI 95% 0.1-3.3) did not elevate the risk for ICH. CONCLUSION: In contrast to common belief, frail patients on OAC with repeated falls show a comparable bleeding rate as in the large RCTs, and the use of OAC did not increase the risk for ICH. However, the number of MBs was low, and of ICHs very low, des

Item does not contain fulltext, 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., 01 juli 2023

Item does not contain fulltext, BACKGROUND AND AIMS: Cancer provides challenges to the continuity of anticoagulant treatment in patients with atrial fibrillation (AF), e.g. through cancer-related surgery or complications. We aimed to provide data on the incidence and reasons for interrupting and discontinuing anticoagulant treatment in AF patients with cancer and to assess its contribution to the risk of thromboembolism (TE) and major bleeding (MB). METHODS: This retrospective study identified AF patients with cancer in two hospitals between 2012 and 2017. Data on anticoagulant treatment, TE and MB were collected during two-year follow-up. Incidence rates (IR) per 100 patient-years and adjusted hazard ratios (aHR) were obtained for TE and MB occurring during on- and off-anticoagulant treatment, during interruption and after resumption, and after permanent discontinuation. RESULTS: 1213 AF patients with cancer were identified, of which 140 patients permanently discontinued anticoagulants and 426 patients experienced one or more interruptions. Anticoagulation was most often interrupted or discontinued due to cancer-related treatment (n = 441, 62 %), bleeding (n = 129, 18 %) or end of life (n = 36, 5 %). The risk of TE was highest off-anticoagulation and during interruptions, with IRs of 19 (14-25)) and 105 (64-13), and aHRs of 3.1 (1.9-5.0) and 4.6 (2.4-9.0), respectively. Major bleeding risk were not only increased during an interruption, but also in the first 30 days after resumption, with IRs of 33 (12-72) and 30 (17-48), and aHRs of 3.3 (1.1-9.8) and 2.4 (1.2-4.6), respectively. CONCLUSIONS: Interruption of anticoagulation therapy harbors high TE and MB risk in AF patients with cancer. The high incidence rates call for better (periprocedural) anticoagulant management strategies tailored to the cancer setting.

Contains fulltext : 300045.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Integrated care is effective in reducing all-cause mortality in patients with atrial fibrillation (AF) in primary care, though time and resource intensive. The aim of the current study was to assess whether integrated care should be directed at all AF patients equally. METHODS: The ALL-IN trial (n = 1,240 patients, median age 77 years) was a cluster-randomized trial in which primary care practices were randomized to provide integrated care or usual care to AF patients aged 65 years and older. Integrated care comprised of (i) anticoagulation monitoring, (ii) quarterly checkups and (iii) easy-access consultation with cardiologists. For the current analysis, cox proportional hazard analysis with all clinical variables from the CHA2DS2-VASc score was used to predict all-cause mortality in the ALL-IN trial. Subsequently, the hazard ratio and absolute risk reduction were plotted as a function of this predicted mortality risk to explore treatment heterogeneity. RESULTS: Under usual care, after a median of 2 years follow-up the absolute risk of all-cause mortality in the highest-risk quarter was 31.0%, compared to 4.6% in the lowest-risk quarter. On the relative scale, there was no evidence of treatment heterogeneity (p for interaction = 0.90). However, there was substantial treatment heterogeneity on the absolute scale: risk reduction in the lowest risk- quarter of risk 3.3% (95% CI -0.4% - 7.0) compared to 12.0% (95% CI 2.7% - 22.0) in the highest risk quarter. CONCLUSION: While the relative degree of benefit from integrated AF care is similar in all patients, patients with a high all-cause mortality risk have a greater benefit on an absolute scale and should therefore be prioritized when implementing integrated care.

Contains fulltext : 300060.pdf (Publisher’s version ) (Open Access), OBJECTIVES: The aim of this multicentre COVID-PREDICT study (a nationwide observational cohort study that aims to better understand clinical course of COVID-19 and to predict which COVID-19 patients should receive which treatment and which type of care) was to determine the association between atrial fibrillation (AF) and mortality, intensive care unit (ICU) admission, complications and discharge destination in hospitalised COVID-19 patients. SETTING: Data from a historical cohort study in eight hospitals (both academic and non-academic) in the Netherlands between January 2020 and July 2021 were used in this study. PARTICIPANTS: 3064 hospitalised COVID-19 patients >18 years old. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the incidence of new-onset AF during hospitalisation. Secondary outcomes were the association between new-onset AF (vs prevalent or non-AF) and mortality, ICU admissions, complications and discharge destination, performed by univariable and multivariable logistic regression analyses. RESULTS: Of the 3064 included patients (60.6% men, median age: 65 years, IQR 55-75 years), 72 (2.3%) patients had prevalent AF and 164 (5.4%) patients developed new-onset AF during hospitalisation. Compared with patients without AF, patients with new-onset AF had a higher incidence of death (adjusted OR (aOR) 1.71, 95% CI 1.17 to 2.59) an ICU admission (aOR 5.45, 95% CI 3.90 to 7.61). Mortality was non-significantly different between patients with prevalent AF and those with new-onset AF (aOR 0.97, 95% CI 0.53 to 1.76). However, new-onset AF was associated with a higher incidence of ICU admission and complications compared with prevalent AF (OR 6.34, 95% CI 2.95 to 13.63, OR 3.04, 95% CI 1.67 to 5.55, respectively). CONCLUSION: New-onset AF was associated with an increased incidence of death, ICU admission, complications and a lower chance to be discharged home. These effects were far less pronounced in patients with prevalent AF. Therefore, new-ons

Contains fulltext : 296917.pdf (Publisher’s version ) (Open Access), BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherla

Item does not contain fulltext, Background Patients with atrial fibrillation (AF) are frequently treated with apixaban 2.5-mg twice daily (BID) off-label, presumably to reduce the bleeding risk. However, this approach has the potential to increase the risk of ischemic stroke. If a single measurement could reliably identify patients with high drug levels, the increased stroke risk may be mitigated by confining off-label dose reduction to such patients. Objectives This study aimed to determine whether a single high apixaban level is predictive of a similarly high level when the test is repeated in 2 months. Methods In this prospective cohort study of clinic patients receiving apixaban 5-mg BID for AF or venous thromboembolism, peak and trough apixaban levels were measured using the STA-Liquid anti-Xa assay at baseline and 2 months. We calculated the proportions of patients with levels that remained in the upper quintile. Results Of 100 enrolled patients, 82 came for a second visit, 55 of whom were treated with apixaban 5-mg BID. Seven (63.6%, 95% confidence interval [CI]: 35.4-84.8%) and nine (81.8%, 95% CI: 52.3-94.9%) of 11 patients with a baseline trough and peak level in the upper quintile, respectively, had a subsequent level that remained within this range. Only one (9.1%, 95% CI: 1.6-37.7%) patient had a subsequent level that fell just lower than the median. Conclusion The trough and peak levels of apixaban in patients who have a high level on a single occasion, usually remain high when the assay is repeated in 2 months. Accordingly, the finding of a high apixaban level in patients deemed to be at high risk of bleeding, allows physicians contemplating off-label use of the 2.5-mg BID dose to limit its use to selected patients who are less likely to be exposed to an increased risk of thrombosis.

Contains fulltext : 288926.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 283509.pdf (Publisher’s version ) (Open Access), AIMS: To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. METHODS AND RESULTS: In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01-1.02], lower renal function (OR: 0.96 per ml/min/1.73 m(2), 0.92-0.98), lower weight (OR: 0.98 per kg, 0.97-1.00), active malignancy (OR: 2.46, 1.19-5.09), anaemia (OR: 1.73, 1.08-2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57-9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88-0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m(2), 0.96-1.00). CONCLUSION: In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

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Contains fulltext : 283517.pdf (Publisher’s version ) (Open Access), AIMS: The Routine vs. Aggressive risk factor driven upstream rhythm Control for prevention of Early persistent atrial fibrillation (AF) in heart failure (HF) (RACE 3) trial demonstrated that targeted therapy of underlying conditions improved sinus rhythm maintenance at 1 year. We now explored the effects of targeted therapy on the additional co-primary endpoints; sinus rhythm maintenance and cardiovascular outcome at 5 years. METHODS AND RESULTS: Patients with early persistent AF and mild-to-moderate stable HF were randomized to targeted or conventional therapy. Both groups received rhythm control therapy according to guidelines. The targeted group additionally received four therapies: angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (ARBs), statins, mineralocorticoid receptor antagonists (MRAs), and cardiac rehabilitation. The presence of sinus rhythm and cardiovascular morbidity and mortality at 5-year follow-up were assessed. Two hundred and sixteen patients consented for long-term follow-up, 107 were randomized to targeted and 109 to conventional therapy. At 5 years, MRAs [76 (74%) vs. 10 (9%) patients, P < 0.001] and statins [81 (79%) vs. 59 (55%), P < 0.001] were used more in the targeted than conventional group. Angiotensin-converting enzyme inhibitors/ARBs and physical activity were not different between groups. Sinus rhythm was present in 49 (46%) targeted vs. 43 (39%) conventional group patients at 5 years (odds ratio 1.297, lower limit of 95% confidence interval 0.756, P = 0.346). Cardiovascular mortality and morbidity occurred in 20 (19%) in the targeted and 15 (14%) conventional group patients, P = 0.353. CONCLUSION: In patients with early persistent AF and HF superiority of targeted therapy in sinus rhythm maintenance could not be preserved at 5-year follow-up. Cardiovascular outcome was not different between groups. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00877643.

Contains fulltext : 245690.pdf (Publisher’s version ) (Open Access), BACKGROUND: The Prevention of Arrhythmia Device Infection Trial (PADIT) investigated whether intensification of perioperative prophylaxis could prevent cardiac implantable electronic device (CIED) infections. Compared with a single dose of cefazolin, the perioperative administration of cefazolin, vancomycin, bacitracin, and cephalexin did not significantly decrease the risk of infection. Our objective was to compare the microbiology of infections between study arms in PADIT. METHODS: This was a post hoc analysis. Differences between study arms in the microbiology of infections were assessed at the level of individual patients and at the level of microorganisms using the Fisher exact test. RESULTS: Overall, 209 microorganisms were reported from 177 patients. The most common microorganisms were coagulase-negative staphylococci (CoNS; 82/209 [39.2%]) and S. aureus (75/209 [35.9%]). There was a significantly lower proportion of CoNS in the incremental arm compared with the standard arm (30.1% vs 46.6%; P = .04). However, there was no significant difference between study arms in the frequency of recovery of other microorganisms. In terms of antimicrobial susceptibility, 26.5% of microorganisms were resistant to cefazolin. CoNS were more likely to be cefazolin-resistant in the incremental arm (52.2% vs 26.8%, respectively; P = .05). However, there was no difference between study arms in terms of infections in which the main pathogen was sensitive to cefazolin (77.8% vs 64.3%; P = .10) or vancomycin (90.8% vs 90.2%; P = .90). CONCLUSIONS: Intensification of the prophylaxis led to significant changes in the microbiology of infections, despite the absence of a decrease in the overall risk of infections. These findings provide important insight on the physiopathology of CIED infections. TRIAL REGISTRATION: NCT01002911.

Contains fulltext : 234172.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Studies on the use of non-vitamin K antagonist oral anticoagulants in unselected patients with atrial fibrillation (AF) show that clinical characteristics and dosing practices differ per region, but lack data on edoxaban. METHODS: With data from Edoxaban Treatment in routiNe clinical prActice for patients with AF in Europe (ETNA-AF-Europe), a large prospective observational study, we compared clinical characteristics (including the dose reduction criteria for edoxaban: creatinine clearance 15-50 ml/min, weight ≤60 kg, and/or use of strong p‑glycoprotein inhibitors) of patients from Belgium and the Netherlands (BeNe) with those from other European countries (OEC). RESULTS: Of all 13,639 patients in ETNA-AF-Europe, 2579 were from BeNe. BeNe patients were younger than OEC patients (mean age: 72.3 vs 73.9 years), and had lower CHA(2)DS(2)-VASc (mean: 2.8 vs 3.2) and HAS-BLED scores (mean: 2.4 vs 2.6). Patients from BeNe less often had hypertension (61.6% vs 80.4%), and/or diabetes mellitus (17.3% vs 23.1%) than patients from OEC. Moreover, relatively fewer patients in BeNe were prescribed the reduced dose of 30 mg edoxaban (14.8%) than in OEC (25.4%). Overall, edoxaban was dosed according to label in 83.1% of patients. Yet, 30 mg edoxaban was prescribed in the absence of any dose reduction criteria in 36.9% of 30 mg users (5.5% of all patients) in BeNe compared with 35.5% (9.0% of all patients) in OEC. CONCLUSION: There were several notable differences between BeNe and OEC regarding clinical characteristics and dosing practices in patients prescribed edoxaban, which are relevant for the local implementation of dose evaluation and optimisation. TRIAL REGISTRATION: NCT02944019; Date of registration 24 October 2016.

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Contains fulltext : 235287.pdf (Publisher’s version ) (Open Access), AIMS: Syncope care is often fragmented and inefficient. Structuring syncope care through implementation of guidelines and Syncope Units has been shown to improve diagnostic yield, reduce costs and improve quality of life. We implemented the European Society of Cardiology (ESC) 2018 syncope guidelines at the Emergency Departments (ED) and established Syncope Units in five Dutch hospitals. We evaluated the implementation process by identifying factors that hinder ('barriers') and facilitate ('facilitators') the implementation. METHODS AND RESULTS: We conducted, recorded and transcribed semi-structured interviews with 19 specialists and residents involved in syncope care from neurology, cardiology, internal medicine and emergency medicine. Two researchers independently classified the reported barriers and facilitators, according to the framework of qualitative research (Flottorp), which distinguished several separate fields ('levels'). Software package Atlas.ti was used for analysis. We identified 31 barriers and 22 facilitators. Most barriers occurred on the level of the individual health care professional (e.g. inexperienced residents having to work with the guideline at the ED) and the organizational context (e.g. specialists not relinquishing preceding procedures). Participants reported most facilitators at the level of innovation (e.g. structured work-flow at the ED). The multidisciplinary Syncope Unit was welcomed as useful solution to a perceived need in clinical practice. CONCLUSION: Implementing ESC syncope guidelines at the ED and establishing Syncope Units facilitated a structured multidisciplinary work-up for syncope patients. Most identified barriers related to the individual health care professional and the organizational context. Future implementation of the multidisciplinary guideline should be tailored to address these barriers.

Contains fulltext : 225355.pdf (Publisher’s version ) (Open Access), In recent years, as more and more experience has been gained with prescribing direct oral anticoagulants (DOACs), new research initiatives have emerged in the Netherlands to improve the safety and appropriateness of DOAC treatment for stroke prevention in patients with atrial fibrillation (AF). These initiatives address several contemporary unresolved issues, such as inappropriate dosing, non-adherence and the long-term management of DOAC treatment. Dutch initiatives have also contributed to the development and improvement of risk prediction models. Although fewer bleeding complications (notably intracranial bleeding) are in general seen with DOACs in comparison with vitamin K antagonists, to successfully identify patients with high bleeding risk and to tailor anticoagulant treatment accordingly to mitigate this increased bleeding risk, is one of the research aims of recent and future years. This review highlights contributions from the Netherlands that aim to address these unresolved issues regarding the anticoagulant management in AF in daily practice, and provides a narrative overview of contemporary stroke and bleeding risk assessment strategies.

Contains fulltext : 225394.pdf (Publisher’s version ) (Open Access), Aims: Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression. Methods and results: In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 ± 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5–4.4) years, CHA2DS2-VASc 1.9 ± 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression. Conclusions: In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number. Trial registration number: Clinicaltrials.gov identifier NCT02726698.

Contains fulltext : 220887.pdf (publisher's version ) (Open Access), Background: For the improvement of AF care, it is important to gain insight into current anticoagulation prescription practices and guideline adherence. This report focuses on the largest Dutch subset of AF-patients, derived from the GARFIELD-AF registry. Methods: Across 35 countries worldwide, patients with newly diagnosed 'non-valvular' atrial fibrillation (AF) with at least one additional risk factor for stroke were included. Dutch patients were enrolled in five, independent, consecutive cohorts from 2010 until 2016. Results: In the Netherlands, 1189 AF-patients were enrolled. The prescription of non-vitamin K antagonist oral anticoagulants (NOAC) has increased sharply, and as per 2016, more patients were initiated on NOACs instead of vitamin K antagonists (VKA). In patients with a class I recommendation for anticoagulation, only 7.5% compared to 30.0% globally received no anticoagulation. Reasons for withholding anticoagulation in these patients were unfortunately often unclear. Conclusions: The data from the GARFIELD-AF registry shows the rapidly changing anticoagulation preference of Dutch physicians in newly diagnosed AF. Adherence to European AF guidelines in terms of anticoagulant regimen would appear to be appropriate. In absence of structured follow up of AF patients on NOAC, the impact of these rapid practice changes in anticoagulation prescription in the Netherlands remains to be established.

Contains fulltext : 225502.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, Objective: To determine the diagnostic yield of repeated screening for atrial fibrillation (AF) among geriatric patients. Methods: A pragmatic prospective cohort study into applying opportunistic screening for AF with a handheld single lead ECG device (SLD) in a geriatric cohort. Consecutive patients of 65 years old and older visiting the geriatric outpatient clinic were eligible for inclusion. A 12 lead ECG was performed, followed by measurements with the SLD during every visit to the geriatric outpatient clinic. A frailty index was based on the accumulation of deficits model. Results: 478 patients were eligible. Patients were excluded if they did not give informed consent (17 patients), had a pacemaker or implantable cardioverter defibrillator (20 patients), or had incomplete medical files (two patients). After exclusion, 439 patients participated in this study. The mean age was 78 years (range 65 to 100 years), 54% were female. AF was known in 89 patients (20%), first detected on the baseline ECG in four patients (1%) and first detected with the SLD in 20 patients (5%) during follow up visits. Sensitivity of the SLD was 90.0%, specificity 99.0%, negative predictive value 99.7%, and positive predictive value 73.5%. Most patients (82%) with AF were frail and 53% were severely frail. Conclusion: Repeated screening in geriatric patients has a five times higher diagnostic yield than usual care. It was easily combined with usual care. Because of the positive predictive value of 73.5%, it remains necessary to confirm AF with a 12 lead ECG or 24-h Holter monitoring.

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Contains fulltext : 229205.pdf (publisher's version ) (Open Access)

Background: Atrial fibrillation (AF) is common in chronic heart failure (HF) patients and influences the choice and effects of drug and device therapy. In this large real-world HF registry, we studied whether the presence of AF affects the prescription of guideline-recommended HF therapy. Methods: We analyzed 8253 patients with chronic HF with reduced ejection fraction (HFrEF) from 34 Dutch outpatient clinics included in the period between 2013 and 2016 treated according to the 2012 ESC guidelines. Results: 2109 (25.6%) of these patients were in AF (mean age 76.8 ± 9.2 years, 65.0% were men) and 6.144 (74.4%) had no AF (mean age 70.7 ± 12.2 years, 63.6% were men). Patients with AF more often received beta-blockers (81.7% vs. 79.7%, p = 0.04), MRAs (57.1% vs. 51.7%, p < 0.01), diuretics (89.7% vs. 80.6%, p < 0.01) and digoxin (40.1% vs. 9.3%, p < 0.01) compared to patients without AF, whereas they less often receive renin-angiotensin-system (RAS)-inhibitors (76.1% vs. 83.1%, p < 0.01). The number of patients who received beta-blockers, RAS-inhibitor and MRA at ≥50% of the recommended target dose was comparable between those with and without AF (16.6% vs. 15.2%, p = 0.07). Conclusion: In this large cohort of chronic HFrEF patients, the prevalence of AF was high and we observed significant differences in prescription of both guideline-recommended HF between patients with and without AF.

Contains fulltext : 202675.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Cardiac implantable electronic device infection is a major complication that usually requires device removal. PADIT (Prevention of Arrhythmia Device Infection Trial) was a large cluster crossover trial of conventional versus incremental antibiotics. OBJECTIVES: This study sought to investigate independent predictors of device infection in PADIT and develop a novel infection risk score. METHODS: In brief, over 4 6-month periods, 28 centers used either conventional or incremental prophylactic antibiotic treatment in all patients. The primary outcome was hospitalization for device infection within 1 year (blinded endpoint adjudication). Multivariable logistic prediction modeling was used to identify the independent predictors and develop a risk score for device infection. The prediction models were internally validated with bootstrap methods. RESULTS: Device procedures were performed in 19,603 patients, and hospitalization for infection occurred in 177 (0.90%) within 1 year of follow-up. The final prediction model identified 5 independent predictors of device infection (prior procedures [P], age [A], depressed renal function [D], immunocompromised [I], and procedure type [T]) with an optimism-corrected C-statistic of 0.704 (95% confidence interval: 0.660 to 0.744). A PADIT risk score ranging from 0 to 15 points classified patients into low (0 to 4), intermediate (5 to 6) and high (>/=7) risk groups with rates of hospitalization for infection of 0.51%, 1.42%, and 3.41%, respectively. CONCLUSIONS: This study identified 5 independent predictors of device infection and developed a novel infection risk score in the largest cardiac implantable electronic device trial to date, warranting validation in an independent cohort. The 5 independent predictors in the PADIT score are readily adopted into clinical practice. (Prevention of Arrhythmia Device Infection Trial [PADIT Pilot]; NCT01002911).

Contains fulltext : 191924.pdf (publisher's version ) (Open Access)