Reduced dementia risk in patients with optimized anticoagulation therapy undergoing atrial fibrillation ablation.

BACKGROUND: Atrial fibrillation (AF) is associated with the development of dementia, and observational studies have shown that oral anticoagulation and catheter ablation reduce dementia risk. However, such studies did not consistently report on periprocedural anticoagulation and long-term oral anticoagulation coverage, for which reason the separate effect of AF ablation on dementia risk could not be established. OBJECTIVE: We evaluated the protective effect of AF ablation in a large cohort of patients who received optimized anticoagulation and compared them with patients who were managed medically. METHODS: We retrospectively included 5912 consecutive patients who underwent first-time catheter ablation for AF between 2008 and 2018 and compared them with 52,681 control individuals from the Swedish Patient Register. Propensity score matching produced 2 cohorts of equal size (n = 3940) with similar baseline characteristics. Dementia diagnosis was identified by International Classification of Diseases codes from the patient register. RESULTS: Most propensity score-matched patients were taking an oral anticoagulant at the start (94.5%) and end (75.0%) of the study. Mean follow-up was 4.9 ± 2.8 years. Catheter ablation was associated with lower risk for the dementia diagnosis compared with the control group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.86; P = .017). The result was similar when including patients with a stroke diagnosis before inclusion (HR, 0.50; 95% CI, 0.28-0.89; P = .019) and after adjustment for the competing risk of death (HR, 0.41; 95% CI, 0.20-0.86; P = .018). CONCLUSION: Catheter ablation of AF in patients with optimized oral anticoagulation therapy was associated with a reduction in dementia diagnosis, even after adjustment for potential confounders and for competing risk of death.

Challenges and lessons learned from a long-term postauthorisation safety study programme of rivaroxaban in Europe.

OBJECTIVES: To describe opportunities and challenges experienced from the four pharmacoepidemiological database studies included in the rivaroxaban post authorisation safety study (PASS) programme and propose ways to maximise the value of population-based observational research when addressing regulatory requirements. DESIGN: PASS programme of rivaroxaban carried out as part of the regulatory postapproval commitment to the European Medicines Agency. SETTING: Clinical practice in Germany, the Netherlands, Sweden and the UK (electronic health records)-undertaken by pharmacoepidemiology research teams using country-specific databases with different coding structures. PARTICIPANTS: 355 152 patients prescribed rivaroxaban and 338 199 patients prescribed vitamin K antagonists. RESULTS: Two major challenges that were encountered throughout the lengthy PASS programme were related to: (1) finalising country-tailored study designs before the extent of rivaroxaban uptake was known, and (2) new research questions that arose during the programme (eg, those relating to an evolving prescribing landscape). RECOMMENDATIONS: We advocate the following strategies to help address these major challenges (should they arise in any future PASS): conducting studies based on a common data model that enable the same analytical tools to be applied when using different databases; maintaining early, clear, continuous communication with the regulator (including discussing the potential benefit of studying drug use as a precursor to planning a safety study); consideration of adaptive designs whenever uncertainty exists and following an initial period of data collection; and setting milestones for the review of study objectives.

Association between catheter ablation of atrial fibrillation and mortality or stroke.

OBJECTIVE: Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. METHODS: We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. RESULTS: Patients who underwent catheter ablation were healthier (mean CHA2DS2-VASc score 1.4±1.4 vs 1.6±1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5±2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). CONCLUSIONS: Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality.

Cost-effectiveness of population screening for atrial fibrillation: the STROKESTOP study.

AIMS: Previous studies on the cost-effectiveness of screening for atrial fibrillation (AF) are based on assumptions of long-term clinical effects. The STROKESTOP study, which randomised 27 975 persons aged 75/76 years into a screening invitation group and a control group, has a median follow-up time of 6.9 years. The aim of this study was to estimate the cost-effectiveness of population-based screening for AF using clinical outcomes. METHODS AND RESULTS: The analysis is based on a Markov cohort model. The prevalence of AF, the use of oral anticoagulation, clinical event data, and all-cause mortality were taken from the STROKESTOP study. The cost for clinical events, age-specific utilities, utility decrement due to stroke, and stroke death was taken from the literature. Uncertainty in the model was considered in a probabilistic sensitivity analysis. Per 1000 individuals invited to the screening, there were 77 gained life years and 65 gained quality-adjusted life years. The incremental cost was €1.77 million lower in the screening invitation group. Gained quality-adjusted life years to a lower cost means that the screening strategy was dominant. The result from 10 000 Monte Carlo simulations showed that the AF screening strategy was cost-effective in 99.2% and cost-saving in 92.7% of the simulations. In the base-case scenario, screening of 1000 individuals resulted in 10.6 [95% confidence interval (CI): -22.5 to 1.4] fewer strokes (8.4 ischaemic and 2.2 haemorrhagic strokes), 1.0 (95% CI: -1.9 to 4.1) more cases of systemic embolism, and 2.9 (95% CI: -18.2 to 13.1) fewer bleedings associated with hospitalization. CONCLUSION: Based on the STROKESTOP study, this analysis shows that a broad AF screening strategy in an elderly population is cost-effective. Efforts should be made to increase screening participation.

Prognostic implication of premature ventricular contractions in patients without structural heart disease.

AIMS: Premature ventricular contractions (PVCs) are a common form of arrhythmia associated with an unfavourable prognosis in patients with structural heart disease. However, the prognostic significance in absence of heart disease is debated. With this study, we aim to investigate whether subjects with PVC, without structural heart disease, have a worse prognosis than the general population. METHODS AND RESULTS: Patients evaluated for PVC at a secondary care centre in Stockholm County from January 2010 to December 2016 were identified. We included patients without history of previous heart disease who had undergone echocardiography and exercise test with normal findings. Based on sex and age, we matched the PVC cohort to a four times bigger control group from the general population and compared the outcome in terms of mortality and cardiovascular morbidity during a median follow-up time of 5.2 years. We included 820 patients and 3,264 controls. Based on a non-inferiority analysis, the PVC group did not have a higher mortality than the control group (0.44, CI 0.27-0.72). Sensitivity analysis with propensity score matching confirmed this result. CONCLUSIONS: PVC patients, who after thorough evaluation showed no signs of structural heart disease, did not have a worse prognosis when compared to an age- and sex- control group based on the general population.

Stroke Risk Stratification in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting.

Background The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long-term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new-onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2-VASc scoring system for estimating the 1-year ischemic stroke risk in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new-onset postoperative atrial fibrillation and without oral anticoagulation after first-time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry-based observational cohort study. The 1-year ischemic stroke rate at each step of the CHA2DS2-VASc score was estimated using a Kaplan-Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow-up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2-VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results. Conclusions Patients with new-onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2-VASc score <3 have such a low 1-year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.

Prognostic impact of type 1 and type 2 diabetes mellitus in atrial fibrillation and the effect of severe hypoglycaemia: a nationwide cohort study.

AIMS: To compare prognosis between individuals without diabetes, type 1 and type 2 diabetes in a nationwide atrial fibrillation cohort in Sweden and study the significance of severe hypoglycaemia. METHODS: Using data from all-inclusive national registers, 309,611 patients with non-valvular atrial fibrillation were enrolled during 2013-2014. Of these, 2,221 had type 1 and 58,073 had type 2 diabetes. Patients were followed for all-cause mortality until 27 March 2017, and for myocardial infarction, ischaemic stroke and first-ever diagnosis of heart failure or dementia until 31 December 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox and competing risk regression. RESULTS: Using individuals without diabetes as reference (HR = 1), the adjusted HRs in type 1 vs. type 2 diabetes were for mortality 1.87 (CI 1.73-2.02) vs. 1.51 (CI 1.47-1.55), heart failure 1.59 (CI 1.42-1.78) vs. 1.41 (CI 1.34-1.48), myocardial infarction 2.49 (CI 2.17-2.85) vs. 1.70 (CI 1.59-1.81), ischaemic stroke 1.59 (CI 1.35-1.87) vs. 1.31 (CI 1.22-1.40), and dementia 1.46 (CI 1.15-1.85) vs. 1.28 (CI 1.18-1.40). Among individuals with type 2 diabetes, those with previous severe hypoglycaemia had increased risk of mortality (HR 1.26; CI 1.17-1.36) and dementia (HR 1.37; CI 1.08-1.73) compared with those without previous severe hypoglycaemia. CONCLUSION: Presence of diabetes-regardless of type- in atrial fibrillation is associated with an increased risk of premature death, cardiovascular events and dementia. This increase is more pronounced in type 1 than in type 2 diabetes. A history of severe hypoglycaemia is associated with a worsened prognosis in type 2 diabetes.

Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Impaired fasting glucose: a risk factor for atrial fibrillation and heart failure.

BACKGROUND: Dysglycaemia is associated with overall cardiovascular disease even at prediabetes levels. The aim of this study was to explore the association between glucose levels and future risk of developing atrial fibrillation and heart failure, respectively. METHODS: In this prospective cohort study subjects from the Swedish AMORIS-cohort with fasting glucose from health examinations 1985-1996 without previous cardiovascular disease (N = 294,057) were followed to 31 December 2011 for incident atrial fibrillation or heart failure. Cox proportional hazard models with attained age as timescale and adjustments for sex, cholesterol, triglycerides, and socioeconomic status were used to estimate hazard ratios by glucose categorized groups (normal glucose 3.9-6.0 mmol/L, impaired fasting glucose; 6.1-6.9 mmol/L, undiagnosed diabetes ≥ 7.0 mmol/L, and diagnosed diabetes). RESULTS: During a mean follow-up time of 19.1 years 28,233 individuals developed atrial fibrillation and 25,604 developed heart failure. The HR for atrial fibrillation was 1.19 (95% confidence interval 1.13-1.26) for impaired fasting glucose, 1.23 (1.15-1.32) for undiagnosed diabetes and 1.30 (1.21-1.41) for diagnosed diabetes. Corresponding figures for heart failure were; 1.40 (1.33-1.48), 2.11 (1.99-2.23), 2.22 (2.08-2.36) respectively. In a subset with BMI data (19%), these associations were attenuated and for atrial fibrillation only remained statistically significant among subjects with diagnosed diabetes (HR 1.25; 1.02-1.53). CONCLUSIONS: Fasting glucose at prediabetes levels is associated with development of atrial fibrillation and heart failure. To some extent increased BMI may drive this association.

Clinical outcomes in systematic screening for atrial fibrillation (STROKESTOP): a multicentre, parallel group, unmasked, randomised controlled trial.

BACKGROUND: Atrial fibrillation is a leading cause of ischaemic stroke. Early detection of atrial fibrillation can enable anticoagulant therapy to reduce ischaemic stroke and mortality. In this randomised study in an older population, we aimed to assess whether systematic screening for atrial fibrillation could reduce mortality and morbidity compared with no screening. METHODS: STROKESTOP was a multicentre, parallel group, unmasked, randomised controlled trial done in Halland and Stockholm in Sweden. All 75-76-year-olds residing in these two regions were randomly assigned (1:1) to be invited to screening for atrial fibrillation or to a control group. Participants attended local screening centres and those without a history of atrial fibrillation were asked to register intermittent electrocardiograms (ECGs) for 14 days. Treatment with oral anticoagulants was offered if atrial fibrillation was detected or untreated. All randomly assigned individuals were followed up in the intention-to-treat analysis for a minimum of 5 years for the primary combined endpoint of ischaemic or haemorrhagic stroke, systemic embolism, bleeding leading to hospitalisation, and all-cause death. This trial is registered with ClinicalTrials.gov, NCT01593553. FINDINGS: From March 1, 2012, to May 28, 2014, 28 768 individuals were assessed for eligibility and randomly assigned to be invited to screening (n=14 387) or the control group (n=14 381). 408 individuals were excluded from the intervention group and 385 were excluded from the control group due to death or migration before invitation. There was no loss to follow-up. Of those invited to screening, 7165 (51·3%) of 13 979 participated. After a median follow-up of 6·9 years (IQR 6·5-7·2), significantly fewer primary endpoint events occurred in the intervention group (4456 [31·9%] of 13 979; 5·45 events per 100 years [95% CI 5·52-5·61]) than in the control group (4616 [33·0%] of 13 996; 5·68 events per 100 years [5·52-5·85]; hazard ratio 0·96 [95% CI 0·92-1·00]; p=0·045). INTERPRETATION: Screening for atrial fibrillation showed a small net benefit compared with standard of care, indicating that screening is safe and beneficial in older populations. FUNDING: Stockholm County Council, the Swedish Heart & Lung Foundation, King Gustav V and Queen Victoria's Freemasons' Foundation, the Klebergska Foundation, the Tornspiran Foundation, the Scientific Council of Halland Region, the Southern Regional Healthcare Committee, the Swedish Stroke Fund, Carl Bennet AB, Boehringer Ingelheim, Bayer, and Bristol Myers Squibb-Pfizer.

Prognostic Implications of Supraventricular Arrhythmias.

The aim of this study was to establish the prevalence and prognostic implication of progressive supraventricular arrhythmias from frequent supraventricular ectopic complexes, isolated, in bi- or trigeminy, to supraventricular tachycardias with different characteristics. In the STROKESTOP I mass-screening study for atrial fibrillation (AF) in 75- and 76-year olds in Sweden, participants registered 30-second intermittent ECG twice daily for two weeks. The ECG-recordings from STROKESTOP I were re-evaluated using an automated algorithm to detect individuals with frequent supraventricular ectopic complexes or runs. Detected episodes were manually re-examined to confirm the findings. The primary endpoint was AF as ascertained from the national Swedish Patient register. Exploratory secondary endpoints were stroke and death. Median follow-up was 4.2 (interquartile range [IQR] 3.8-4.4) years. Of the examined 6,100 participants, 85% were free of significant supraventricular arrhythmia. In the 894 participants that had arrhythmia, frequent supraventricular ectopic complexes were the most common arrhythmia, n = 709 (11.6%) and irregular supraventricular tachycardias were more common than regular. Individuals with the most AF similar supraventricular tachycardias, irregular and lacking p-waves (termed micro-AF), n = 97 (1.6%) had the highest risk of developing AF (hazard ratio 4.3; 95% confidence interval [CI] 2.7-6.8). They also had increased risk of death (hazard ratio 2.0; CI 1.1-3.8). In conclusion, progression of atrial arrhythmias from supraventricular ectopic complexes to more AF-like episodes is associated with development of AF. Extended screening for AF should be considered in individuals with frequent supraventricular activity, especially in those with supraventricular tachycardias with AF characteristics.

Atrial Fibrillation, Oral Anticoagulants, and Concomitant Active Cancer: Benefits and Risks.

Aim To determine to what extent active cancer influences the benefit-risk relationship among patients with atrial fibrillation receiving oral anticoagulants for stroke prevention. Methods In this cohort study of all patients with atrial fibrillation in the Swedish Patient register during 2006 to 2017, 8,228 patients with active cancer and 323,394 without cancer were followed up to 1 year after initiation of oral anticoagulants. Cox regression models, adjusting for confounders and the competing risk of death, were used to assess risk of cerebrovascular and bleeding events. Results Among patients treated with oral anticoagulants, the risk for cerebrovascular events did not differ between cancer patients and noncancer patients (subhazard ratio [sHR]: 1.12, 95% confidence interval [CI]: 0.98-1.29). Cancer patients had a higher risk for bleedings (sHR: 1.69, CI: 1.56-1.82), but not for fatal bleedings (sHR: 1.17, CI: 0.80-1.70). Use of nonvitamin K oral anticoagulants was associated with lower risk of both cerebrovascular events and bleedings compared with warfarin. Conclusion Patients with atrial fibrillation and active cancer appear to have similar net cerebrovascular benefit of oral anticoagulant treatment to patients without cancer, despite an increased risk of nonfatal bleedings. Use of nonvitamin K oral anticoagulants was associated with lower risk of all studied outcomes.

Performance of pulse palpation compared to one-lead ECG in atrial fibrillation screening.

BACKGROUND: The 2020 European Society of Cardiology atrial fibrillation guidelines recommend opportunistic screening for atrial fibrillation by pulse taking or ECG rhythm strip in those aged over 65 years. HYPOTHESIS: We aimed to compare the diagnostic accuracy of pulse palpation to ECG rhythm strip when screening for atrial fibrillation. A secondary aim was to investigate whether participants with palpitations were more likely to be diagnosed with new atrial fibrillation. METHODS: The study population were 75/76 year old individuals that participated in the STROKESTOP II study, a Swedish screening study for atrial fibrillation. Pulse palpation of the radial pulse for 30 sec was performed by healthcare professionals and recorded as regular or irregular. Thereafter a 30-sec single-lead ECG was registered. Patients were asked also if they had a history of palpitations. RESULTS: Of the 6159 participants included in the study, 461 (7.5%) had irregular pulse. Twenty-two (4.8%) of those with irregular pulse were diagnosed with atrial fibrillation on single-lead ECG rhythm strip. Among those with regular pulse, 6 (0.1%) cases of new atrial fibrillation were found. The sensitivity of the pulse palpation test was 78.6% and positive predictive value 4.8%. The proportion of newly diagnosed atrial fibrillation was not different between those with and without history of palpitations. CONCLUSION: Pulse palpation was inferior to single-lead ECG when screening for atrial fibrillation. We therefore advocate the use of single-lead ECG rather than pulse palpation when screening for atrial fibrillation. Palpitations did not predict atrial fibrillation.

New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting and Long-Term Outcome: A Population-Based Nationwide Study From the SWEDEHEART Registry.

Background The long-term impact of new-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early-initiated oral anticoagulation (OAC) in patients with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population-based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new-onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long-term outcome in patients with and without POAF, and potential associations between early-initiated OAC and outcome. In a cohort of 24 523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30 days after surgery. During follow-up (median 4.5 years, range 0‒9 years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.18 [95% CI, 1.05‒1.32]), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all-cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82). Conclusions POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.

A diagnosis of atrial fibrillation is not a predictor for pulmonary embolism.

BACKGROUND AND OBJECTIVES: Atrial fibrillation causes stroke by embolization of blood clots from the left atrium. This suggests that it also can cause pulmonary embolism through embolization of thrombi from the right atrium. Our objective was to investigate if atrial fibrillation is an independent risk factor for pulmonary embolism. METHOD: This is a retrospective registry study of a random sample of 1.5 million Swedish residents alive on January 1, 2010 (n = 1,442,028) who were followed until the end of 2017. Information about comorbidity, medication and outcomes was obtained from the Swedish national health registers. The endpoint was a first-time event of pulmonary embolism. RESULTS: The group with atrial fibrillation was >25 years older (mean) than the group without and had almost three times higher incidence of pulmonary embolism (2.91 and 1.09 per 1000 year at risk, p < 0.001). After adjustment for age and other co-factors, atrial fibrillation without oral anticoagulant protection was not associated with increased risk for pulmonary embolism (HR 1.03, CI 0.94-1.13). Adjustment for the competing risk of dying showed similar results (sHR 0.99, CI 0.70-1.40). The higher rate of pulmonary embolism among patients with atrial fibrillation can be fully explained by differences in age and comorbidity. CONCLUSION: A diagnosis of atrial fibrillation is not a predictor for pulmonary embolism.

Rationale and design of a European epidemiological post-authorization safety study (PASS) program: rivaroxaban use in routine clinical practice.

BACKGROUND: Rivaroxaban is a highly selective factor Xa inhibitor approved for use in Europe for multiple indications. STUDY DESIGN AND METHODS: The European rivaroxaban epidemiological post-authorization safety study (PASS) program consists of seven complementary observational studies. For four of the studies, data are obtained from health-care databases in the UK, the Netherlands, Germany, and Sweden. These database studies describe patterns of rivaroxaban use and patient characteristics over time, and investigate safety and effectiveness outcomes in new users of rivaroxaban using a cohort analysis and nested case-control analysis. To put these results in context, safety outcomes are also analyzed in new users of standard of care. In addition, a modified prescription event monitoring study conducted in the early post-launch phase in primary care, and two specialist cohort event monitoring studies that investigated rivaroxaban use in the secondary care hospital setting, systematically collected drug utilization and safety data via questionnaires completed by health-care professionals in the UK. DISCUSSION: The European rivaroxaban epidemiological PASS is a comprehensive program of complementary studies generating evidence from patients treated in routine clinical practice that will expand our understanding of the risk-benefit profile of rivaroxaban.

Brief episodes of rapid irregular atrial activity (micro-AF) are a risk marker for atrial fibrillation: a prospective cohort study.

BACKGROUND: Short supraventricular tachycardias with atrial fibrillation (AF) characteristics are associated with an increased risk of developing AF over time. The aim of this study is to determine if presence of very short-lasting episodes of AF-like activity (micro-AF) can also be used as a marker of undiagnosed silent atrial fibrillation. METHODS: In the STROKESTOP II study, a Swedish mass screening study for AF among 75- and 76-year-olds, participants with NT-proBNP ≥125 ng/L performed intermittent ECG recordings 30 s, four times daily for 2 weeks. Participants with micro-AF (sudden onset of irregular tachycardia with episodes of ≥5 consecutive supraventricular beats and total absence of p-waves, lasting less than 30 s) were invited to undergo extended AF screening using continuous event recording for 2 weeks. A control group of individuals without micro-AF was examined using the same ECG modalities. RESULTS: Out of 3763 participants in STROKESTOP II who had elevated NT-proBNP levels and were free of AF, n = 221 (6%) had micro-AF. The majority of participants with micro-AF (n = 196) accepted further investigation with continuous ECG monitoring which showed presence of AF in 26 of them. In the control group (n = 250), continuous monitoring detected 7 new AF cases. Thus, AF was significantly more common in the micro AF group (13%) compared to the control group (3%), p < 0.001. CONCLUSIONS: Presence of short-lasting episodes of AF-like activity (micro-AF) indicates increased likelihood for undetected AF. Continuous screening therefore seems recommendable if a finding of AF would change clinical management. TRAIL REGISTRATION: ClinicalTrials.gov, identifier: NCT02743416, registered April 19, 2016.

Clinical and echocardiographic characteristics of individuals aged 75/76 years old with screening-detected elevated NT-proBNP levels.

Background: High plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) indicate increased probability of congestive heart failure (CHF) and atrial fibrillation (AF) and are associated with poor prognosis. Objective: We aimed to describe the clinical and echocardiographic characteristics of a population of individuals aged 75/76 years old with NT-proBNP ≥900 ng/L without previously known CHF or AF. Methods: All individuals aged 75/76 years in the Stockholm region were randomised to a screening study for AF. Half of them were invited to screening. Of those invited, 49.5% agreed to participate. Individuals with NT-proBNP ≥900 ng/L without known CHF were invited for further clinical evaluation. Results: Among 6315 participants without AF who had NT-proBNP sampled, 102 without previously known CHF had ≥900 ng/L. Of these, 93 completed further clinical investigations. In the population that was clinically investigated, 53% were female, and the median NT-proBNP was 1200 ng/L. New AF was found in 28 (30%). The NT-proBNP value in this group was not significantly different from those where AF was not detected (median 1285 vs 1178 ng/L). Patients with newly detected AF had larger left atrial volume and higher pulmonary artery pressure than those without AF. Preserved left ventricular ejection fraction (≥50%) was found in 86% of the participants, mid-range ejection fraction (40%-49%) in 3.2% and reduced ejection fraction (<40%) in 10.8%. Thirteen patients (14%) had other serious cardiac disorders that required medical attention. Conclusion: Elderly individuals with NT-proBNP levels ≥900 ng/L constitute a population at high cardiovascular risk even in the absence of diagnosed CHF or AF, and therefore merit further investigation.

Intermittent vs continuous electrocardiogram event recording for detection of atrial fibrillation-Compliance and ease of use in an ambulatory elderly population.

BACKGROUND: There are many atrial fibrillation (AF) screening devices available. Validation studies have mainly been performed in optimal settings in the young population. HYPOTHESIS: We aim to compare the yield of AF detection, compliance, and patient-based experience in an ambulatory elderly population by using intermittent electrocardiogram (ECG) recordings and continuous event recording simultaneously. METHODS: The study participants were part of the STROKESTOP II study, a Swedish screening study for AF. All participants were 75/76 years of age, were clinically free of AF, and had N-terminal pro b-type natriuretic peptides levels ≥125 ng/L. AF screening was performed in parallel during a 2-week period, using a continuous event recording device (R-test 4; Novacor) and 30-second intermittent recordings using a handheld ECG device (Zenicor II) four times daily. Participants were asked to fill out a questionnaire with regard to compliance and ease of use of the devices. RESULTS: During continuous event recording, 6% (n = 15/269) were diagnosed with AF and intermittent ECG detected AF in 2% (n = 5/269) of the participants (P = .002). No new cases of AF were detected using intermittent ECG monitoring only, but some episodes were detected in parallel for patients. On a graded ordinal scale of 1 to 5, with 1 reflecting "very easy to use", continuous monitoring was graded 2 (interquartile range [IQR]: 1-3) compared to intermittent 1 (IQR: 1-1) (P < .001). CONCLUSION: Continuous event recording detected three times more AF compared to intermittent ECG in an elderly ambulatory population. Compliance and user-friendliness were rated higher for the intermittent ECG device.

Stepwise mass screening for atrial fibrillation using N-terminal B-type natriuretic peptide: the STROKESTOP II study.

AIMS: To study the prevalence of unknown atrial fibrillation (AF) in a high-risk, 75/76-year-old, population using N-terminal B-type natriuretic peptide (NT-proBNP) and handheld electrocardiogram (ECG) recordings in a stepwise screening procedure. METHODS AND RESULTS: The STROKESTOP II study is a population-based cohort study in which all 75/76-year-old in the Stockholm region (n = 28 712) were randomized 1:1 to be invited to an AF screening programme or to serve as the control group. Participants without known AF had NT-proBNP analysed and were stratified into low-risk (NT-proBNP <125 ng/L) and high-risk (NT-proBNP ≥125 ng/L) groups. The high-risk group was offered extended ECG-screening, whereas the low-risk group performed only one single-lead ECG recording. In total, 6868 individuals accepted the screening invitation of which 6315 (91.9%) did not have previously known AF. New AF was detected in 2.6% [95% confidence interval (CI) 2.2-3.0] of all participants without previous AF. In the high-risk group (n = 3766/6315, 59.6%), AF was diagnosed in 4.4% (95% CI 3.7-5.1) of the participants. Out of these, 18% had AF on their index-ECG. In the low-risk group, one participant was diagnosed with AF on index-ECG. The screening procedure resulted in an increase in known prevalence from 8.1% to 10.5% among participants. Oral anticoagulant treatment was initiated in 94.5% of the participants with newly diagnosed AF. CONCLUSION: N-terminal B-type natriuretic peptide-stratified systematic screening for AF identified 4.4% of the high-risk participants with new AF. Oral anticoagulant treatment initiation was well accepted in the group diagnosed with new AF.