Ischemic Stroke Temporally Associated With New-Onset Atrial Fibrillation: A Population-Based Registry-Linkage Study.

BACKGROUND: Limited data exist on the temporal relationship between new-onset atrial fibrillation (AF) and ischemic stroke and its impact on patients' clinical characteristics and mortality. METHODS: A population-based registry-linkage database includes all patients with new-onset AF in Finland from 2007 to 2018. Ischemic stroke temporally associated with AF (ISTAF) was defined as an ischemic stroke occurring within ±30 days from the first AF diagnosis. Clinical factors associated with ISTAF were studied with logistic regression and 90-day survival with Cox proportional hazards analysis. RESULTS: Among 229 565 patients with new-onset AF (mean age, 72.7 years; 50% female), 204 774 (89.2%) experienced no ischemic stroke, 12 209 (5.3%) had past ischemic stroke >30 days before AF, and 12 582 (5.8%) had ISTAF. The annual proportion of ISTAF among patients with AF decreased from 6.0% to 4.8% from 2007 to 2018. Factors associated positively with ISTAF were higher age, lower education level, and alcohol use disorder, whereas vascular disease, heart failure, chronic kidney disease cancer, and psychiatric disorders were less probable with ISTAF. Compared with patients without ischemic stroke and those with past ischemic stroke, ISTAF was associated with ≈3-fold and 1.5-fold risks of death (adjusted hazard ratios, 2.90 [95% CI, 2.76-3.04] and 1.47 [95% CI, 1.39-1.57], respectively). The 90-day survival probability of patients with ISTAF increased from 0.79 (95% CI, 0.76-0.81) in 2007 to 0.89 (95% CI, 0.87-0.91) in 2018. CONCLUSIONS: ISTAF depicts the prominent temporal clustering of ischemic strokes surrounding AF diagnosis. Despite having fewer comorbidities, patients with ISTAF had worse, albeit improving, survival than patients with a history of or no ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537. URL: https://www.encepp.eu; Unique identifier: EUPAS29845.

Primary care indicators for disease burden, monitoring and surveillance of COVID-19 in 31 European countries: Eurodata Study.

BACKGROUND: During the COVID-19 pandemic, the majority of patients received ambulatory treatment, highlighting the importance of primary health care (PHC). However, there is limited knowledge regarding PHC workload in Europe during this period. The utilization of COVID-19 PHC indicators could facilitate the efficient monitoring and coordination of the pandemic response. The objective of this study is to describe PHC indicators for disease surveillance and monitoring of COVID-19's impact in Europe. METHODS: Descriptive, cross-sectional study employing data obtained through a semi-structured ad hoc questionnaire, which was collectively agreed upon by all participants. The study encompasses PHC settings in 31 European countries from March 2020 to August 2021. Key-informants from each country answered the questionnaire. Main outcome: the identification of any indicator used to describe PHC COVID-19 activity. RESULTS: Out of the 31 countries surveyed, data on PHC information were obtained from 14. The principal indicators were: total number of cases within PHC (Belarus, Cyprus, Italy, Romania and Spain), number of follow-up cases (Croatia, Cyprus, Finland, Spain and Turkey), GP's COVID-19 tests referrals (Poland), proportion of COVID-19 cases among respiratory illnesses consultations (Norway and France), sick leaves issued by GPs (Romania and Spain) and examination and complementary tests (Cyprus). All COVID-19 cases were attended in PHC in Belarus and Italy. CONCLUSIONS: The COVID-19 pandemic exposes a crucial deficiency in preparedness for infectious diseases in European health systems highlighting the inconsistent recording of indicators within PHC organizations. PHC standardized indicators and public data accessibility are urgently needed, conforming the foundation for an effective European-level health services response framework against future pandemics.

Mental health conditions and risk of first-ever ischaemic stroke and death in patients with incident atrial fibrillation: A nationwide cohort study.

BACKGROUND: Atrial fibrillation (AF) patients with mental health conditions (MHCs) have higher incidence of ischaemic stroke (IS) than patients without MHC, but whether this results from direct impact of MHCs or relates to higher prevalence of comorbidities and differences in the use of oral anticoagulant (OAC) therapy is unclear. We assessed the hypothesis that MHCs independently increase the risk of IS in patients with incident AF. METHODS: The nationwide FinACAF cohort covered all 203,154 patients diagnosed with incident AF without previous IS or transient ischaemic attack in Finland during 2007-2018. MHCs of interest were depression, bipolar disorder, anxiety disorder, schizophrenia and any MHC. The outcomes were first-ever IS and all-cause death. RESULTS: The patients' (mean age 73.0 ± 13.5 years, 49.0% female) mean follow-up time was 4.3 (SD 3.3) years and 16,272 (8.0%) experienced first-ever IS and 63,420 (31.2%) died during follow-up. After propensity score matching and adjusting for OAC use, no MHC group was associated with increased IS risk (adjusted SHRs (95% CI): depression 0.961 (0.857-1.077), bipolar disorder 1.398 (0.947-2.006), anxiety disorder 0.878 (0.718-1.034), schizophrenia 0.803 (0.594-1.085) and any MHC 1.033 (0.985-1.085)). Lower rate of OAC use partly explained the observed higher crude IS incidence in patients with any MHC. Depression, schizophrenia and any MHC were associated with higher all-cause mortality (adjusted HRs [95% CI]: 1.208 [1.136-1.283], 1.543 [1.352-1.761] and 1.149 [1.116-1.175], respectively). CONCLUSIONS: In this nationwide retrospective cohort study, MHCs were not associated with the incidence of first-ever IS in patients with AF.

Poor Quality of Warfarin Treatment Increases the Risk of All Types of Intracranial Hemorrhage in Atrial Fibrillation.

BACKGROUND: Intracranial hemorrhage (ICH) is a devastating complication of oral anticoagulation. The aim of this study was to describe the spectrum of ICH and to evaluate the association of warfarin control with the risk of ICH in a nationwide cohort of unselected atrial fibrillation (AF) patients. Methods and Results: The FinWAF is a retrospective registry-linkage study. Data were collected from several nationwide Finnish health-care registers and laboratory databases. The primary outcome was any ICH (traumatic or non-traumatic). The quality of warfarin therapy was assessed continuously by calculating the time in therapeutic range in a 60-day window (TTR60). Adjusted Cox proportional hazard models were used. A total of 53,953 patients were included (53% men; mean age, 73 years; mean follow-up, 2.94 years; mean TTR, 63%). In 129,684 patient-years, 1,196 patients had ICH (non-traumatic, 53.5%; traumatic, 43.6%; traumatic subdural, 38.6%); crude annual rate, 0.92%; 95% CI: 0.87-0.98). A lower TTR60 was significantly associated with higher risk of ICH (TTR60 ≤40% vs. TTR60 >80%; adjusted hazard ratio, 2.16; 95% CI: 1.83-2.54). Other variables independently associated with ICH included age >65 years, previous stroke, male sex, low hemoglobin, thrombocytopenia, elevated alanine aminotransferase, and previous bleeding other than ICH. CONCLUSIONS: Poor control of warfarin treatment was associated with elevated risk of ICH. Approximately half of the ICH were traumatic, mainly subdural.

Quality of prior warfarin therapy in ischemic stroke patients with a pre-stroke diagnosis of atrial fibrillation.

In atrial fibrillation (AF), warfarin prevents ischemic strokes (IS), but its implementation varies. We conducted a retrospective registry study on clinical features and prior warfarin therapy in AF patients with IS. Of our 540 patients, 143 had a prior diagnosis of AF, of which 51% used warfarin. Warfarin use was more common in those having permanent than paroxysmal AF (76% versus 36%, p<0.001). On admission, 42% had INR within the therapeutic range. Average TTR was 64%. Advanced age (p=0.009) and permanent AF (p<0.001) were associated with higher TTR. Better warfarin therapy quality was associated with advanced age and permanent AF.

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.

Exploring the accessibility of primary health care data in Europe's COVID-19 response: developing key indicators for managing future pandemics (Eurodata study).

BACKGROUND: Primary Health Care (PHC) plays a crucial role in managing the COVID-19 pandemic, with only 8% of cases requiring hospitalization. However, PHC COVID-19 data often goes unnoticed on European government dashboards and in media discussions. This project aims to examine official information on PHC patient care during the COVID-19 pandemic in Europe, with specific objectives: (1) Describe PHC's clinical pathways for acute COVID-19 cases, including long-term care facilities, (2) Describe PHC COVID-19 pandemic indicators, (3) Develop COVID-19 PHC activity indicators, (4) Explain PHC's role in vaccination strategies, and (5) Create a PHC contingency plan for future pandemics. METHODS: A mixed-method study will employ two online questionnaires to gather retrospective PHC data on COVID-19 management and PHC involvement in vaccination strategies. Validation will occur through focus group discussions with medical and public health (PH) experts. A two-wave Delphi survey will establish a European PHC indicators dashboard for future pandemics. Additionally, a coordinated health system action plan involving PHC, secondary care, and PH will be devised to address future pandemic scenarios. ANALYSIS: Quantitative data will be analysed using STATA v16.0 for descriptive and multivariate analyses. Qualitative data will be collected through peer-reviewed questionnaires and content analysis of focus group discussions. A Delphi survey and multiple focus groups will be employed to achieve consensus on PHC indicators and a common European health system response plan for future pandemics. The Eurodata research group involving researchers from 28 European countries support the development. DISCUSSION: While PHC manages most COVID-19 acute cases, data remains limited in many European countries. This study collects data from numerous countries, offering a comprehensive perspective on PHC's role during the pandemic in Europe. It pioneers the development of a PHC dashboard and health system plan for pandemics in Europe. These results may prove invaluable in future pandemics. However, data may have biases due to key informants' involvement and may not fully represent all European GP practices. PHC has a significant role in the management of the COVID-19 pandemic, as most of the cases are mild or moderate and only 8% needed hospitalization. However, PHC COVID-19 activity data is invisible on governments' daily dashboards in Europe, often overlooked in media and public debates.

Clinical pathway of COVID-19 patients in primary health care in 30 European countries: Eurodata study.

BACKGROUND: Most COVID-19 patients were treated in primary health care (PHC) in Europe. OBJECTIVES: To demonstrate the scope of PHC workflow during the COVID-19 pandemic emphasising similarities and differences of patient's clinical pathways in Europe. METHODS: Descriptive, cross-sectional study with data acquired through a semi-structured questionnaire in PHC in 30 European countries, created ad hoc and agreed upon among all researchers who participated in the study. GPs from each country answered the approved questionnaire. Main variable: PHC COVID-19 acute clinical pathway. All variables were collected from each country as of September 2020. RESULTS: COVID-19 clinics in PHC facilities were organised in 8/30. Case detection and testing were performed in PHC in 27/30 countries. RT-PCR and lateral flow tests were performed in PHC in 23/30, free of charge with a medical prescription. Contact tracing was performed mainly by public health authorities. Mandatory isolation ranged from 5 to 14 days. Sick leave certification was given exclusively by GPs in 21/30 countries. Patient hotels or other resources to isolate patients were available in 12/30. Follow-up to monitor the symptoms and/or new complementary tests was made mainly by phone call (27/30). Chest X-ray and phlebotomy were performed in PHC in 18/30 and 23/30 countries, respectively. Oxygen and low-molecular-weight heparin were available in PHC (21/30). CONCLUSION: In Europe PHC participated in many steps to diagnose, treat and monitor COVID-19 patients. Differences among countries might be addressed at European level for the management of future pandemics.

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

Low socioeconomic status has been associated with poor outcomes in patients with atrial fibrillation (AF). However, little is known about socioeconomic disparities in adherence to stroke prevention with direct oral anticoagulants (DOACs). We assessed the hypothesis that AF patients with higher income or educational levels have better adherence to DOACs in terms of treatment implementation and persistence. The used nationwide registry-based FinACAF cohort covers all patients with incident AF starting DOACs in Finland during 2011-2018. The implementation analyses included 74 222 (mean age 72.7 ± 10.5 years, 50.8% female) patients, and persistence analyses included 67 503 (mean age 75.3 ± 8.9 years, 53.6% female) patients with indication for permanent anticoagulation (CHA2 DS2 -VASc score >1 in men and >2 in women). Patients were divided into income quartiles and into three categories based on their educational attainment. Therapy implementation was measured using the medication possession ratio (MPR), and patients with MPR ≥0.90 were defined adherent. Persistence was measured as the incidence of therapy discontinuation, defined as the first 135-day period without DOAC purchases after drug initiation. Patients with higher income or education were consistently more likely adherent to DOACs in the implementation phase (comparing the highest income or educational category to the lowest: adjusted odds ratios 1.18 (1.12-1.25) and 1.21 (1.15-1.27), respectively). No association with income or educational levels was observed on the incidence of therapy discontinuation. In conclusion, we observed that income and educational levels both have independent positive association on the implementation of DOAC therapy but no association on therapy persistence in patients with AF.

Comprehensive nationwide incidence and prevalence trends of atrial fibrillation in Finland.

OBJECTIVE: Atrial fibrillation (AF) is a worldwide healthcare challenge owing to population ageing. In this study, we assessed the current trends in the incidence and prevalence of AF for the first time in an unselected, nationwide population. METHODS: In the Finnish Anticoagulation in Atrial Fibrillation study, we gathered comprehensive data including all primary, secondary and tertiary healthcare visits and drug reimbursement from national healthcare registers to identify all patients with incident AF between 2004 and 2018 in Finland. Incident AF was defined as new-onset AF occurring after 2007. Time trends for the incidence and prevalence of AF were calculated and stratified by sex and age. RESULTS: A total of 411 387 patients with AF diagnosis were documented in Finland during 2004-2018. In 2018, the incidence and prevalence of AF in the total Finnish population were 469/100 000 and 4.1%, respectively. The incidence of new-onset AF in the adult population (≥20 years) increased from 471/100 000 in 2007 to 604/100 000 in 2018, but the age-adjusted incidence remained stable. The prevalence of AF increased in the adult population from 2.5% to 5.2%, and was higher in men than in women (5.9% vs 4.6%, p<0.001). The incidence and prevalence of AF increased with age and were 3194/100 000 and 23.4% in patients older than 75 years. CONCLUSIONS: Based on comprehensive nationwide data including primary care, we observed an increasing incidence and prevalence of AF over time. This increase was strongly age-dependent with the age-standardised incidence remaining stable during 2007-2018. TRIAL REGISTRATION NUMBER: NCT04645537.

The effect of mental health conditions on the use of oral anticoagulation therapy in patients with atrial fibrillation: the FinACAF study.

AIMS: Little is known about the effects of mental health conditions (MHCs) on the utilization of oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients. We aimed to assess whether MHCs affect initiation of OAC therapy among AF patients with special focus on non-vitamin K antagonist oral anticoagulants (NOACs). METHODS AND RESULTS: The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) registry included all 239 222 patients diagnosed with incident AF during 2007-18 in Finland identified from national registries covering primary to tertiary care and drug purchases. Patients with previous depression, bipolar disorder, anxiety disorder, or schizophrenia diagnosis or a fulfilled psychiatric medication prescription within the year preceding the AF diagnosis were classified to have any MHC. The main outcome was OAC initiation, defined as first fulfilled OAC prescription after AF diagnosis. The patients' mean age was 72.7 years and 49.8% were female. The prevalence of any MHC was 19.9%. A lower proportion of patients with any MHC compared with those without MHCs were initiated on OAC therapy (64.9% vs. 73.3%, P < 0.001). Any MHC was associated with lower incidence of OAC initiation [adjusted subdistribution hazard ratio (aSHR) 0.867; 95% confidence interval (CI) 0.856-0.880], as were depression (aSHR 0.868; 95% CI 0.856-0.880), bipolar disorder (aSHR 0.838; 95% CI 0.824-0.852), anxiety disorder (aSHR 0.840; 95% CI 0.827-0.854), and schizophrenia (aSHR 0.838; 95% CI 0.824-0.851), during the entire follow-up. Any MHC remained associated with impaired incidence of OAC initiation also in the NOAC era during 2015-18 (aSHR 0.821; 95% CI 0.805-0.837). CONCLUSION: MHCs are common among AF patients, and they are associated with a lower rate of OAC initiation even during the NOAC era.

Adherence to oral anticoagulation in ischemic stroke patients with atrial fibrillation.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved. AIMS: We sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF). METHODS: We recruited hospitalised patients (2013-2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA2DS2-VASc and SAMe-TT2R2 scores with poor adherence. RESULTS: Among 396 patients (median age 75.0 years, interquartile range [IQR] 70-80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12-33]; median ARMS score 17 [IQR 17-19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA2DS2-VASc and SAMe-TT2R2 scores were not associated with poor adherence. CONCLUSIONS: Adherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients.KEY MESSAGESAdherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke.Independent patient-related factors rather than composite scores were associated with poor adherence.The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline.