Oral anticoagulant treatment after bioprosthetic valvular intervention or valvuloplasty in patients with atrial fibrillation—A SWEDEHEART study

Aims To describe the prevalence of atrial fibrillation (AF), use of oral anticoagulants (OAC) and change in antithrombotic treatment patterns during follow-up after valve intervention with a biological prosthesis or valvuloplasty. Methods and results All patients with history of AF or new-onset AF discharged alive after valvular intervention (biological prosthesis or valvuloplasty) between 2010–2016 in Sweden were included (n = 7,362). Information about comorbidities was collected from national patient registers. Exposure to OAC was based on pharmacy dispensation data. In total 4,800 (65.2%) patients had a history of AF, and 2,562 (34.8%) patients developed new-onset AF, with 999 (39.0%) developing new-onset AF within 3 months after intervention. The proportion of patients with biological valve prosthesis was higher in patients with new-onset AF compared to history of AF (p<0.001). CHA2DS2-VASc score ≥2 was observed in 83.1% and 75.5% patients with history of AF and new-onset AF, respectively. Warfarin was more frequently dispensed than NOAC at discharge in patients with history of AF (43.9% vs 7.3%), and in patients with new-onset AF (36.6% vs 17.1%). Almost half of the AF population was not dispensed on any OAC at discharge (48.8% in patients with history of AF and 46.3% in patients with new-onset AF). Conclusion In this real world study of patients with AF and recent valvular intervention, risk of new-onset AF after valvular intervention is high emphasizing need for frequent rhythm monitoring after intervention. A considerable undertreatment with OAC was observed despite being indicated for the majority of the patients. Warfarin was the OAC most frequently dispensed.

Differences Between Anticoagulated Patients With Ischemic Stroke Versus Intracerebral Hemorrhage

Background Data on the relative contribution of clinical and neuroimaging risk factors to acute ischemic stroke (AIS) versus intracerebral hemorrhage (ICH) occurring on oral anticoagulant treatment are scarce. Methods and Results Cross‐sectional study was done on consecutive oral anticoagulant–treated patients presenting with AIS, transient ischemic attack (TIA), or ICH from the prospective observational NOACISP (Novel‐Oral‐Anticoagulants‐In‐Stroke‐Patients)‐Acute registry. We compared clinical and neuroimaging characteristics (small vessel disease markers and atherosclerosis) in ICH versus AIS/TIA (reference) using logistic regression. Among 734 patients presenting with stroke on oral anticoagulant treatment (404 [55%] direct oral anticoagulants, 330 [45%] vitamin K antagonists), 605 patients (82%) had AIS/TIA and 129 (18%) had ICH. Prior AIS/TIA, coronary artery disease, dyslipidemia, and worse renal function were associated with AIS/TIA (adjusted odds ratio [aOR] [95% CI] 0.51 [0.32–0.82], 0.48 [0.26–0.86], 0.55 [0.34–0.89], and 0.82 [0.75–0.90] per 10 mL/min). Prior ICH, older age, higher admission blood pressure, and statin treatment were associated with ICH (aOR [95% CI] 6.33 [2.87–14.04], 1.37 [1.04–1.81] per 10 years, 1.19 [1.10–1.29] per 10 mm Hg, and 1.81 [1.09–3.03]). Cerebral microbleeds and moderate‐to‐severe white matter hyperintensities contributed more to ICH (aOR [95% CI] 2.77 [1.34–6.18], and 2.62 [1.28–5.63]). Aortic arch, common and internal carotid artery atherosclerosis, and internal carotid artery stenosis ≥50% contributed more to AIS/TIA (aOR [95% CI] 0.54 [0.31–0.90], 0.29 [0.05–0.97], 0.48 [0.30–0.76], and 0.32 [0.13–0.67]). Conclusions In patients presenting with stroke on oral anticoagulant, AIS/TIA was 5 times more common than ICH. A high atherosclerotic burden (indicated by cardiovascular comorbidities and extracranial atherosclerosis) and prior AIS/TIA contributed more to AIS/TIA, while small vessel disease markers and prior ICH were stronger determinants for ICH. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02353585.

The profile of patients with atrial fibrillation scheduled for cardioversion or catheter ablation hospitalized in a Romanian rehabilitation hospital

Objectives - Structural cardiac, mainly atrial remodeling in non-valvular atrial fibrillation (NVAF) creates conditions for thromboembolic complications, despite the optimization of oral anticoagulant treatment over the past years. This study aims to provide a comparative analysis of patients with NVAF, with and without atrial thrombotic masses, in an integrated approach using clinical, electrocardiographic, anatomohemodynamic cardiac findings assessed by echocardiography, as well as an evaluation of the inflammatory status based on the usual screening blood markers. Methods – The study was based on the anonymous analysis of the medical records of 50 patients with NVAF monitored in a center of cardiology in Cluj-Napoca between March 2019 – February 2020, who received optimal oral anticoagulant treatment, all undergoing transesophageal ultrasound prior to cardioversion or ablation therapy. The statistical data processing methods were based on the “chi square” test and overall model fit logistic regression. Results – Atrial thrombotic complications were found in 7 (14%) patients with NVAF. These had, compared to patients without thrombotic masses, a mean CHA2DS2-VASc scale of 3 versus 2.76 (p=0.05), more frequently other atrial tachyarrhythmias (p<0.01), a more expressed inflammatory reaction (p=0.02), as well as a reduction of LVEF (p<0.01) and the peak left atrial appendage emptying velocity (p<0.01). Conclusions – In addition to a high CHA2DS2-VASc score, left anatomohemodynamic cardiac alteration, atrial arrhythmic complexity and background inflammatory status create conditions for high thromboembolic risk in patients with NVAF. Keywords: non-valvular atrial fibrillation, cardiac thrombosis, left ventricular ejection fraction, inflammatory status, peak left atrial appendage velocity,

Time-to-event comparative effectiveness of NOACs vs VKAs in newly diagnosed non-valvular atrial fibrillation patients.

Objective: To investigate the difference in the time-to-event probabilities of ischaemic events, major bleeding and death of NOAC vs VKAs in newly diagnosed non-valvular atrial fibrillation patients. Design: Retrospective observational cohort study. Setting: UK's Clinical Practice Research Data linked to the Hospital Episode Statistics inpatient and outpatient data, mortality data and the Patient Level Index of Multiple Deprivation. Participants: Patients over 18 years of age, with an initial diagnosis of atrial fibrillation between 1st-Mar-2011 and 31-July-2017, without a record for a valve condition, prosthesis or procedure previous to initial diagnosis, and without a record of oral anticoagulant treatment in the previous year. Intervention: Oral anticoagulant treatment with either vitamin K antagonists (VKAs) or the newer target-specific oral anticoagulants (NOACs). Main Outcome Measures: Ischaemic event, major bleeding event and death from 15 days from initial prescription up to two years follow-up. Statistical Analysis: Treatment effect was defined as the difference in time-to-event probability between NOAC and VKA treatment groups. Treatment and outcomes were modelled using an ensemble of parametric and non-parametric models, and the average and conditional average treatment effects were estimated using one-step Targeted Maximum Likelihood Estimation (TMLE). Heterogeneity of treatment effect was examined using variable importance methods in Bayesian Additive Regression Trees (BART). Results: The average treatment effect of NOAC vs VKA was consistently close to zero across all times, with a temporal average of $0.00[95\%0.00,0.00]$ for ischaemic event, $0.00\%[95\%-0.01,0.01]$ for major bleeding and $0.00[95\%-0.01,0.01]$ for death. Only history of major bleeding was found to influence the distribution of treatment effect for major bleeding, but its impact on the associated conditional average treatment effect was not significant. Conclusions: This study found no statistically significant difference between NOAC and VKA users up to two years of medication use for the prevention of ischaemic events, major bleeding or death.

Impact of the COVID-19 lockdown on the adherence of stroke patients to direct oral anticoagulants: a secondary analysis from the MAAESTRO study

Background The negative impact of the COVID-19 outbreak on stroke care has been reported, but no data exist on the influence of the lockdown on medication adherence to antithrombotic treatment for stroke prevention. We present a comparison of electronic adherence data of stroke patients treated with direct oral anticoagulants (DOAC) prior to and during the COVID-19 lockdown in spring 2020 in Switzerland. Methods This is a secondary analysis using data from the ongoing MAAESTRO study, in which stroke patients with atrial fibrillation electronically monitor their adherence to DOAC treatment. Eligible patients for this analysis had at least four weeks of adherence data prior to and during the COVID-19 lockdown. Three adherence metrics (taking adherence, timing adherence, drug holidays) were calculated and compared descriptively. Results The analysis included eight patients (median age 81.5 years, IQR 74.8–84.5). Five patients had a pre-lockdown taking adherence over 90% (mean 96.8% ± 2.9), with no change during lockdown, high timing adherence in both periods and no drug holidays. The remaining three patients had pre-lockdown taking and timing adherence below 90%. Of those, two patients showed a moderate decline either in taking or timing adherence compared to pre-lockdown. One showed a substantial increase in taking and timing adherence during lockdown (both + 25.8%). Conclusion Our data suggest that a major disruption of social life (i.e., the imposed COVID-19 lockdown) is unlikely to relevantly affect the medication intake behaviour of patients with high pre-established adherence, but might have an impact in patients with previously suboptimal adherence. Trial registration number MAAESTRO: electronic Monitoring and improvement of Adherence to direct oral Anticoagulant treatment—a randomized crossover study of an Educational and reminder-based intervention in ischaemic STROke patients under polypharmacy, NCT03344146.