Comorbidity and medication trends in chronic kidney disease and incident atrial fibrillation - A Nationwide Cohort Study.

Introduction Chronic kidney disease (CKD) is associated with increased incidence of atrial fibrillation (AF). Also, patients with AF are prone to adverse kidney outcomes. We examined comorbidities and medication use in patients with CKD and incident AF. Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide retrospective register-linkage study including data from 168 233 patients with incident AF from 2007 to 2018, with laboratory data from 2010 onwards. Estimated glomerular filtration rate (eGFR) was available for 124 936 patients. The cohort was divided into 5 CKD stages with separate groups for dialysis and kidney transplantation. Results At AF diagnosis eGFR <60ml/min/1.73m2 was found in 27%, while 318 (0.3%) patients were on dialysis, and 188 (0.2%) had a functioning kidney transplant. Lowering eGFR yielded to more comorbidities and medications. During 2010-2018 in patients with eGFR <60ml/min/1.73m2 prevalence of hypertension, dyslipidaemia and diabetes increased from 82% to 88 %, from 50% to 66% and from 25% to 33%, respectively (<0.001). Throughout the observation period, lipid-lowering medication was underused. Conclusions More than one-fourth of patients with incident AF also had CKD stage 3-5 (eGFR <60ml/min/1.73m2). Both comorbidities and medication use increased with worsening kidney function. Prevalence of major cardiovascular (CV) risk factors increased during 2010-2018, but use of survival affecting medications, such as lipid-lowering medication, was suboptimal at all stages of CKD. More attention should be given to the optimal treatment of risk factors in this high CV risk population.

Highly Sensitive Immunoassay for Long Forms of Cardiac Troponin T Using Upconversion Luminescence.

BACKGROUND: Long cardiac troponin T (cTnT) has been proposed to be a promising and more specific biomarker of acute myocardial infarction (AMI). As it represents a subfraction of circulating cTnT, detection of very low concentrations is a requirement. The aim of this study was to develop a novel, highly sensitive immunoassay for long cTnT. METHODS: A two-step sandwich-type immunoassay for long cTnT was developed, utilizing upconverting nanoparticles (UCNPs) as reporters. The limits of detection and quantitation were determined for the assay. Linearity and matrix effects were evaluated. Performance with clinical samples was assessed with samples from patients with non-ST elevation myocardial infarction (NSTEMI, n = 30) and end-stage renal disease (ESRD, n = 37) and compared to a previously developed time-resolved fluorescence (TRF)-based long cTnT assay and a commercial high-sensitivity cTnT assay. RESULTS: The novel assay reached a 28-fold lower limit of detection (0.40 ng/L) and 14-fold lower limit of quantitation (1.79 ng/L) than the previously developed TRF long cTnT assay. Li-heparin and EDTA plasma, but not serum, were found to be suitable sample matrixes for the assay. In a receiver operating characteristics curve analysis, the troponin ratio (long/total cTnT) determined with the novel assay showed excellent discrimination between NSTEMI and ESRD with an area under the curve of 0.986 (95% CI, 0.967-1.000). CONCLUSIONS: By utilizing upconversion luminescence technology, we developed a highly sensitive long cTnT assay. This novel assay can be a valuable tool for investigating the full potential of long cTnT as a biomarker for AMI. ClinicalTrials.gov Registration Number: NCT04465591.

Time-in-therapeutic-range defined warfarin and direct oral anticoagulants in atrial fibrillation: a Nationwide Cohort Study.

BACKGROUND: Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). OBJECTIVE: To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR. MATERIALS AND METHODS: We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548). RESULTS: The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85-2.85), 1.44 (1.18-1.75), 0.60 (0.47-0.77) and 0.72 (0.56-0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88-8.35) and 1.87 (1.41-2.49) in the two poorest TTR groups, 1.44 (1.02-1.93) on rivaroxaban, and 0.58 (0.40-0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group. CONCLUSIONS: The outcome was unsatisfactory in the two lowest TTR quartiles - in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest.

Novel electrocardiographic classification for stroke prediction in atrial fibrillation patients undergoing cardioversion.

BACKGROUND: Abnormal conduction, structure, and function of the atrial myocardium predispose to atrial fibrillation (AF) and stroke. The usefulness of electrocardiographic indices in predicting stroke or systemic embolism (SSE) in patients undergoing cardioversion (CV) for AF remains unknown, especially in those at low estimated risk. OBJECTIVE: We systematically evaluated the performance of various P-wave abnormalities (PWAs) in predicting SSE 30 days after CV (derivation cohort) and in the long term (validation cohort). METHODS: Electrocardiograms (n = 1773) of AF patients undergoing an acute CV were manually reviewed. The 30-day post-CV data were used to derive a composite PWA variable. The electrocardiographic findings were validated by the long-term follow-up of patients with no anticoagulation. Electrocardiograms of 27 CAREBANK study patients with right atrial appendage biopsies were further analyzed for histopathologic validation. RESULTS: During data derivation, the best performance was found with a combination of prolonged P-wave (≥180 ms), deflected P-wave morphology in lead II, biphasic P-waves in inferior leads, or increased P-terminal force (≥80 mm·ms) as markers for extensive PWA. In the validation cohort, 219 of 874 (25.1%) had extensive PWA. During a median follow-up of 4.9 years, there were 51 patients (5.8%) with SSE in total. In a competing risk model, PWA predicted SSE (adjusted hazard ratio, 2.1 per category; 95% CI, 1.4-3.1; P < .001). Areas under the curve for SSE at 3 years were 0.77, 0.79, and 0.86 for PWA, CHA2DS2-VASc, score, and their combination, respectively. On histologic evaluation, extensive PWA was associated with interstitial fibrosis (P = .033). CONCLUSION: Novel electrocardiographic PWA classification provided additional prognostic insight in AF patients.

Ischaemic stroke in women with atrial fibrillation: temporal trends and clinical implications.

BACKGROUND AND AIMS: Female sex has been linked with higher risk of ischaemic stroke (IS) in atrial fibrillation (AF), but no prior study has examined temporal trends in the IS risk associated with female sex. METHODS: The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study included all patients with AF in Finland from 2007 to 2018. Ischaemic stroke rates and rate ratios were computed. RESULTS: Overall, 229 565 patients with new-onset AF were identified (50.0% women; mean age 72.7 years). The crude IS incidence was higher in women than in men across the entire study period (21.1 vs. 14.9 events per 1000 patient-years, P < .001), and the incidence decreased both in men and women. In 2007-08, female sex was independently associated with a 20%-30% higher IS rate in the adjusted analyses, but this association attenuated and became statistically non-significant by the end of the observation period. Similar trends were observed when time with and without oral anticoagulant (OAC) treatment was analysed, as well as when only time without OAC use was considered. The decrease in IS rate was driven by patients with high IS risk, whereas in patients with low or moderate IS risk, female sex was not associated with a higher IS rate. CONCLUSIONS: The association between female sex and IS rate has decreased and become non-significant over the course of the study period from 2007 to 2018, suggesting that female sex could be omitted as a factor when estimating expected IS rates and the need for OAC therapy in patients with AF.

Fibrillatory wave amplitude and thromboembolic risk in non-anticoagulated patients with atrial fibrillation.

BACKGROUND: The benefit of oral anticoagulation in atrial fibrillation (AF) is well established for patients at elevated stroke risk, but less clear for those at intermediate risk. We investigated whether analysis of electrocardiogram (ECG) derived fibrillatory waves (F-waves) could help identify patients at risk for stroke and systemic embolism (SSE). METHODS: The Finnish Cardioversion (FinCV) study included patients not on permanent anticoagulation therapy who underwent cardioversion for an acute AF episode. We identified 739 individuals with a valid ECG and complete follow-up data. The maximum amplitudes of the F-waves in leads II and V1 were manually measured from the pre-procedure ECG. Patients were categorized into fine and coarse F-wave groups. The optimal lead and amplitude threshold for grouping were found in an events per person-years analysis. SSE were identified from the patient medical records until either anticoagulation was prescribed, AF was deemed chronic, the patient had deceased, or the end of follow-up. RESULTS: Overall 37 (5.0%) patients suffered SSE during the median follow-up time of 5.4 years (1.9-10.8). Measured from lead V1 the SSE rates per 100 person-years were 1.5 and 0.7 in fine and coarse F-wave groups, respectively. Fine F-waves were observed in 112 (15.2%). Baseline characteristics were similar between the groups. Fine F-wave predicted SSE in a competing risk analysis (SHR 2.34, 95%CI 1.12-4.87, p = .023). Analyses from lead II did not provide significant results. CONCLUSION: Electrocardiographic F-wave amplitude may provide additional information on stroke risk in patients with paroxysmal AF and borderline indications or contraindications for anticoagulation.

Temporal Relation Between Myocardial Infarction and New-Onset Atrial Fibrillation: Results from a Nationwide Registry Study.

Myocardial infarction (MI) and atrial fibrillation (AF) are commonly seen in the same patient. In this study, we evaluated the temporal relations and prognosis of MI and AF. This is a substudy of the nationwide registry-based Finnish Anticoagulation in Atrial Fibrillation (FinACAF) study, comprising all Finnish patients with new-onset AF from 2010 to 2017. Patients with MI and AF were divided into groups depending on the temporal relation between the disease onsets: (1) MI before AF (MIAF), and (4) no MI. The 1-year mortality in the groups were studied with the Cox proportional hazards model. Of the 153,207 patients with new-onset AF (mean age 72.7 years, 50.0% women), 16,265 (10.6%) were diagnosed with MI. Altogether, 8,889 (54.7%) of the patients with MI were in the MIAF group. Of all MIs, 42.2% were diagnosed within 1 year from new-onset AF. The MI>AF group had the worst survival, with an adjusted hazard ratio for death of 3.08 (confidence interval [CI] 2.89 to 3.27) compared with patients without MI. For the MI

Temporal trends of gender disparities in oral anticoagulant use in patients with atrial fibrillation.

AIMS: To investigate sex-specific temporal trends in the initiation of oral anticoagulant (OAC) therapy among patients diagnosed with atrial fibrillation (AF) in Finland between 2007 and 2018. METHODS: The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) Study included all patients with incident AF in Finland from 2007 to 2018. The primary outcome was the initiation of any OAC therapy. RESULTS: We identified 229,565 patients with new-onset AF (50.0% women; mean age 72.7 years). The initiation of OAC therapy increased continuously during the observation period. While women were more likely to receive OAC therapy overall, after adjusting for age, stroke risk factors and other confounding factors, female sex was associated with a marginally lower initiation of OACs (unadjusted and adjusted hazard ratios comparing women to men: 1.08 (1.07-1.10) and 0.97 (0.96-0.98), respectively). Importantly, the gender disparities in OAC use attenuated and reached parity by the end of the observation period. Furthermore, when only patients eligible for OAC therapy according to the contemporary guidelines were included in the analyses, the gender inequalities in OAC initiation appeared minimal. Implementation of direct OACs for stroke prevention was slightly slower among women. CONCLUSION: This nationwide retrospective cohort study covering all patients with incident AF in Finland from 2007 to 2018 observed that although female sex was initially associated with a lower initiation of OAC therapy, the sex-related disparities resolved over the course of the study period.

Mechanocardiography detects improvement of systolic function caused by resynchronization pacing.

Objective.Cardiac resynchronization therapy (CRT) is commonly used to manage heart failure with dyssynchronous ventricular contraction. CRT pacing resynchronizes the ventricular contraction, while AAI (single-chamber atrial) pacing does not affect the dyssynchronous function. This study compared waveform characteristics during CRT and AAI pacing at similar pacing rates using seismocardiogram (SCG) and gyrocardiogram (GCG), collectively known as mechanocardiogram (MCG).Approach.We included 10 patients with heart failure with reduced ejection fraction and previously implanted CRT pacemakers. ECG and MCG recordings were taken during AAI and CRT pacing at a heart rate of 80 bpm. Waveform characteristics, including energy, vertical range (amplitude) during systole and early diastole, electromechanical systole (QS2) and left ventricular ejection time (LVET), were derived by considering 6 MCG axes and 3 MCG vectors across frequency ranges of >1 Hz, 20-90 Hz, 6-90 Hz and 1-20 Hz.Main results.Significant differences were observed between CRT and AAI pacing. CRT pacing consistently exhibited higher energy and vertical range during systole compared to AAI pacing (p< 0.05). However, QS2, LVET and waveform characteristics around aortic valve closure did not differ between the pacing modes. Optimal differences were observed in SCG-Y, GCG-X, and GCG-Y axes within the frequency range of 6-90 Hz.Significance.The results demonstrate significant differences in MCG waveforms, reflecting improved mechanical cardiac function during CRT. This information has potential implications for predicting the clinical response to CRT. Further research is needed to explore the differences in signal characteristics between responders and non-responders to CRT.

Rural-urban and geographical differences in prognosis of atrial fibrillation in Finland: a nationwide cohort study.

AIMS: Rural-urban disparities have been reported in the outcomes of cardiovascular diseases. We assessed whether rural-urban or other geographical disparities exist in the risk of ischemic stroke (IS) and death in patients with atrial fibrillation (AF) in Finland. METHODS: The registry-based FinACAF cohort study covers all patients with AF from all levels of care in Finland from 2007 to 2018. Patients were divided into rural-urban categories and into hospital districts (HDs) based on their municipality of residence. RESULTS: We identified 222,051 patients (50.1% female; mean age 72.8 years; mean follow-up 3.9 years) with new-onset AF, of whom 15,567 (7.0%) patients suffered IS and 72,565 (32.7%) died during follow-up. The crude IS rate was similar between rural and urban areas, whereas the mortality rate was lower in urban areas (incidence rate ratios (IRRs) with 95% confidence intervals (CIs) 0.97 (0.93-1.00) and 0.92 (0.91-0.93), respectively). However, after adjustments, urban residence was associated with slightly higher IS and mortality rates (IRRs with 95% CIs 1.05 (1.01-1.08) and 1.06 (1.04-1.07), respectively). The highest crude IS rate was in the East Savo HD and the lowest in Åland, whereas the highest crude mortality rate was in the Länsi-Pohja HD and the lowest in the North Ostrobothnia HD (IRRs with 95% CIs compared to Helsinki and Uusimaa HD for IS 1.46 (1.28-1.67) and 0.79 (0.62-1.01), and mortality 1.24 (1.16-1.32) and 0.97 (0.93-1.00), respectively. CONCLUSIONS: Rural-urban differences in prognosis of AF in Finland appear minimal, whereas considerable disparities exist between HDs.

Antithrombotic Medication and Major Complications After Mechanical Aortic Valve Replacement.

Patients with mechanical aortic valve replacement (AVR) require lifelong vitamin K antagonist (VKA) therapy for stroke and systemic embolism prevention. However, VKA treatment predisposes patients to various types of bleeding. In the present study, we sought to assess the success of antithrombotic therapy and the occurrence and timing of strokes and bleeding events after mechanical AVR. A total of 308 patients who underwent isolated mechanical AVR were included in the study, and follow-up data were completed for 306 patients (99.4%). The median follow-up time was 7.3 (interquartile range 4.2 to 10.9) years. The risk for major bleeding was 5-fold compared with major stroke (6.2% vs 1.3% and 20.9% vs 4.0%, respectively; events rates 3.1 vs 0.5 per 100 patient-years, respectively) at 30-day and long-term follow-up, indicating good efficacy but inadequate safety of stroke prevention. At the time of the early postoperative major bleeding, the international normalized ratio was under the therapeutic range in 73.7% of the patients. However, most patients were on triple antithrombotic treatment consisting of subcutaneous enoxaparin, VKA, and a tail effect of discontinued aspirin. During the long-term follow-up, the most common site of bleeding was gastrointestinal (41.7%), followed by genitourinary bleeding (23.3%) and intracranial hemorrhage (18.3%). Furthermore, mortality was relatively high, with a 10-year survival estimate of 78.3%. In conclusion, although ischemic stroke is a well-identified adverse event after mechanical AVR, it seems that major bleeding is a frequent clinically relevant complication during perioperative and long-term follow-up. This finding underscores the recognition and management of modifiable bleeding risk factors.

Machine learning-based prediction of in-hospital death for patients with takotsubo syndrome: The InterTAK-ML model.

AIMS: Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles. METHODS AND RESULTS: A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), a sensitivity of 0.85 (0.78-0.95) and a specificity of 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort. CONCLUSION: A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death.

Geographical Variation in the Use of Oral Anticoagulation and Clinical Outcomes among Patients with Atrial Fibrillation in Denmark, Sweden, and Finland.

Background Geographical mapping of variations in the treatment and outcomes of a disease is a valuable tool for identifying inequity. We examined international and intranational variations in initiating oral anticoagulation (OAC) therapy and clinical outcomes among patients with atrial fibrillation (AF) in Nordic countries. We also tracked real-world trends in initiating OAC and the clinical outcomes. Methods We conducted a registry-based multinational cohort study of OAC-naive patients with an incident hospital diagnosis of AF in Denmark ( N = 61,345), Sweden ( N = 124,120), and Finland ( N = 59,855) and a CHA 2 DS 2 -VASc score of ≥1 in men and ≥2 in women between 2012 and 2017. Initiation of OAC therapy was defined as dispensing at least one prescription between 90 days before and 90 days after the AF diagnosis. Clinical outcomes included ischemic stroke, intracerebral hemorrhage, intracranial bleeding, other major bleeding, and all-cause mortality. Results The proportion of patients initiating OAC therapy ranged from 67.7% (95% CI: 67.5-68.0) in Sweden to 69.6% (95% CI: 69.2-70.0) in Finland, with intranational variation. The 1-year risk of stroke varied from 1.9% (95% CI: 1.8-2.0) in Sweden and Finland to 2.3% (95% CI: 2.2-2.4) in Denmark, with intranational variation. The initiation of OAC therapy increased with a preference for direct oral anticoagulants over warfarin. The risk of ischemic stroke decreased with no increase in intracranial and intracerebral bleeding. Conclusion We documented inter- and intranational variation in initiating OAC therapy and clinical outcomes across Nordic countries. Adherence to structured care of patients with AF could reduce future variation.

Oral Anticoagulant Therapy and Risk of Admission to Long-Term Care in patients With Atrial Fibrillation: A Nationwide Cohort Study.

OBJECTIVES: The impact of oral anticoagulants (OACs) on the need of long-term care (LTC) in the aging and multimorbid population of patients with atrial fibrillation (AF) is unknown. We conducted a nationwide cohort study to evaluate the effect of OACs on the need of LTC. DESIGN: Retrospective nationwide cohort study. SETTING AND PARTICIPANTS: The registry-based FinACAF cohort study covers all patients with incident AF from all levels of care in Finland from 2007 to 2018, as well as all their OAC purchases, LTC admissions, and information on previous home care acuity. METHODS: Incidence rate ratios (IRRs) of LTC admission were calculated using Poisson regression models with a Lexis-type data structure based on 3 time scales: follow-up time from AF diagnosis, calendar year, and age. RESULTS: We identified 188,752 patients (49.0% female; mean age 71.4 years; mean follow-up 3.6 years) with incident AF without prior LTC, of whom 143,534 (76.0 %) initiated OAC therapy and 11,775 (6.2 %) were admitted to LTC. OAC therapy was associated with lower rates of LTC admission (adjusted IRR 0.79, 95% CI 0.76-0.82). When compared to warfarin, direct oral anticoagulants (DOACs) were associated with lower LTC admission rate (adjusted IRR 0.69, 95% CI 0.61-0.79). No significant disparities were observed between different DOACs. CONCLUSIONS AND IMPLICATIONS: OAC therapy, particularly with DOACs, is associated with a substantially lower risk of admission to LTC in patients with AF. Increasing guideline-based OAC coverage among patients with AF may prevent the need of LTC, lengthen survival at home, and potentially decrease health care costs.

Geographical variation in persistence to oral anticoagulation therapy and clinical outcomes among patients with atrial fibrillation initiating therapy in Denmark, Sweden, Norway and Finland.

AIM: To examine inter-national and regional variations in persistence of oral anticoagulation (OAC) therapy and incidence of clinical outcomes and mortality, among patients with incident atrial fibrillation (AF) in the Nordic countries. METHODS: We conducted a registry-based multinational cohort study of OAC-naïve patients diagnosed with AF that redeemed at least one prescription of OAC after AF in Denmark (N = 25 585), Sweden (N = 59 455), Norway (N = 40 046) and Finland (N = 22 415). Persistence was dispensing at least one prescription of OAC from Day 365 after the first prescription and 90 days forward. RESULTS: Persistence was 73.6% (95% confidence interval 73.0-74.1) in Denmark, 71.1% (70.7-71.4) in Sweden, 89.3% (88.2-90.1) in Norway and 68.6% (68.0-69.3) in Finland. One-year risk of ischemic stroke varied between 2.0% (1.8-2.1) in Norway and 1.5% (1.4-1.6) in Sweden and 1.5% (1.3-1.6) in Finland. One-year risk of major bleeding other than intracranial bleeding varied between 2.1% (1.9-2.2) in Norway and 5.9% (5.6-6.2) in Denmark. One-year mortality risk varied between 9.3% (8.9-9.6) in Denmark and 4.2% (4.0-4.4) in Norway. CONCLUSION: In OAC-naïve patients with incident AF, persistence of OAC therapy and clinical outcomes vary across Denmark, Sweden, Norway and Finland. Initiation of real-time efforts are warranted to ensure uniform high-quality care across nations and regions.

Aortic Stenosis and Outcomes in Patients With Atrial Fibrillation: A Nationwide Cohort Study.

Background Patients with aortic stenosis (AS) have been underrepresented in the trials evaluating direct oral anticoagulants (DOACs) in atrial fibrillation (AF). We aimed to assess whether AS impacts outcomes in patients with AF and estimate the effects of DOACs versus warfarin in patients with AF and AS. Methods and Results The registry-based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covered all patients with AF diagnosed during 2007 to 2018 in Finland. Hazard ratios (HRs) of first-ever gastrointestinal bleeding, intracranial bleeding, any bleeding, ischemic stroke, and death were estimated with cause-specific hazards regression adjusted for anticoagulant exposure variables. We identified 183 946 patients (50.5% women; mean age, 71.7 [SD, 13.5] years) with incident AF without prior bleeding or ischemic stroke, of whom 5231 (2.8%) had AS. The crude incidence rate of all outcomes was higher in patients with AS than in patients without AS. After propensity score matching, AS was associated with the hazard of any bleeding, gastrointestinal bleeding, and death but not with intracranial bleeding or ischemic stroke (adjusted HRs, 1.36 [95% CI, 1.25-1.48], 1.63 [95% CI, 1.43-1.86], 1.32 [95% CI, 1.26-1.38], 0.96 [95% CI, 0.78-1.17], and 1.11 [95% CI, 0.99-1.25], respectively). Among patients with AS, DOACs were associated with a lower risk of ischemic stroke when compared with warfarin, while bleeding and mortality did not differ between DOACs and warfarin. Conclusions AS is associated with substantially higher risk of gastrointestinal bleeding in patients with AF. DOACs may be more effective in preventing ischemic stroke than warfarin in patients with AF and AS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537.

Trends in treatment and outcomes of atrial fibrillation during 2007-17 in Finland.

AIMS: Guidelines on the management of atrial fibrillation (AF) have evolved significantly during the past two decades, but the concurrent developments in real-life management and prognosis of AF are unknown. We assessed trends in the treatment and outcomes of patients with incident AF between 2007 and 2017. METHODS AND RESULTS: The registry-based nationwide FinACAF (Finnish AntiCoagulation in Atrial Fibrillation) cohort covers all patients with AF in Finland from all levels of care. We determined the proportion of patients who were treated with oral anticoagulants (OACs) or rhythm control therapies, experienced an ischaemic stroke or bleeding event requiring hospitalization, or died within 1-year follow-up after AF diagnosis. We identified 206 909 patients (mean age 72.6 years) with incident AF. During the study period, use of OACs increased from 43.6 to 76.3%, and the increase was most evident in patients with at least moderate stroke risk. One-year mortality decreased from 13.3 to 10.6%, and the ischaemic stroke rate from 5.3 to 2.2%. The prognosis especially improved in patients over 75 years of age. Concurrently, a small increase in major bleeding events was observed. Use of catheter ablation increased continuously over the study period, but use of other rhythm-control therapies decreased after 2013. CONCLUSION: Stroke prevention with OACs in patients with incident AF improved considerably from 2007 to 2017 in Finland. This development was accompanied by decreasing 1-year mortality and the reduction of the ischaemic stroke rate by more than half, particularly among elderly patients, whereas there was only slight increase in severe bleeding events.

Association of income and educational levels on initiation of oral anticoagulant therapy in patients with incident atrial fibrillation: A Finnish nationwide cohort study.

AIMS: Socioeconomic disparities have been reported in the outcomes of patients with atrial fibrillation (AF). We assessed the hypothesis that AF patients with higher income or educational level are more frequently initiated with oral anticoagulant (OAC) therapy for stroke prevention. METHODS: The nationwide registry-based Finnish AntiCoagulation in Atrial Fibrillation cohort covers all patients with AF from all levels of care in Finland. Patients were divided into income quartiles according to their highest annual income during 2004-2018 and into three categories based on educational attainment. The outcome was the first redeemed OAC prescription. RESULTS: We identified 239 222 patients (mean age 72.7 ± 13.2 years, 49.8% female) with incident AF during 2007-2018. Higher income was associated with higher OAC initiation rate: compared to the lowest income quartile the adjusted SHRs (95% CI) for OAC initiation were 1.09 (1.07-1.10), 1.13 (1.11-1.14) and 1.13 (1.12-1.15) in the second, third and fourth income quartiles, respectively. Patients in the highest educational category had a slightly lower OAC initiation rate than patients in the lowest educational category (adjusted SHR 0.92 [95% CI 0.90-0.93]). Income-related disparities were larger and education-related disparities only marginal among patients at high risk of ischemic stroke. The socioeconomic disparities in OAC initiation within 1-year follow-up decreased from 2007 to 2018. The adoption of direct OACs as the initial anticoagulant was faster among patients with higher income or educational levels. CONCLUSION: These findings highlight potential missed opportunities in stroke prevention, especially among AF patients with low income, whereas the education-related disparities in OAC initiation appear controversial.