Sex- and age-specific differences in the use of antiarrhythmic therapies among atrial fibrillation patients: a nationwide cohort study.

BACKGROUND AND AIMS: Atrial fibrillation (AF) patients frequently require active rhythm control therapy to maintain sinus rhythm and reduce symptom burden. Our study assessed whether antiarrhythmic therapies (AATs) are used disproportionately between men and women after new-onset AF. METHODS: The nationwide Finnish anticoagulation in atrial fibrillation (FinACAF) registry-based linkage study covers all patients with new-onset AF in Finland during 2007-2018. Study outcomes included initiation of AATs in the form of antiarrhythmic drugs (AAD), cardioversion, or catheter ablation. RESULTS: The study population constituted of 229 565 patients (50% females). Women were older than men (76.6 ± 11.8 vs. 68.9 ± 13.4 years) and had higher prevalence of hypertension or hyperthyroidism, but lower prevalence of vascular disease, diabetes, renal disease, and cardiomyopathies than men. Overall, 17.6% of women and 25.1% of men were treated with any AAT. Women were treated with AADs more often than men in all age groups (adjusted subdistribution hazard ratio (aSHR) 1.223, 95%-CI 1.187-1.261). Cardioversions were also performed less often on women than on men aged <65 years (aSHR 0.722, 95%-CI 0.695-0.749), more often in patients ≥75 years (aSHR 1.166, 95%-CI 1.108-1.227), while no difference between the sexes existed in patients aged 65-74 years. Ablations were performed less often in women aged <65 years (aSHR 0.908, 95%-CI 0.826-0.998) and ≥75 years (aSHR 0.521, 95%-CI 0.354-0.766), whereas there was no difference in patients aged 65-74 years. CONCLUSION: Women used more AAD than men in all age groups but underwent fewer cardioversion and ablation procedures when aged <65 years.

Temporal trends in mortality and causes of death in patients with incident atrial fibrillation: a nationwide register study from 2010 to 2018.

OBJECTIVES: Atrial fibrillation (AF) is associated with increased mortality. Previous studies have reported conflicting results in temporal trends of mortality after AF diagnosis. We aim to address this disparity by investigating the 1-year mortality and causes of death in Finnish patients diagnosed with AF between 2010 and 2017. DESIGN: The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study is a nationwide retrospective register-based cohort study. SETTING: The FinACAF study has gathered information on all Finnish AF patients between 2004 and 2018, with information from all national healthcare registers and data from all levels of care (primary, secondary and tertiary care). PARTICIPANTS: We included patients with an incident AF diagnosis (International Classification of Diseases, 10th Revision code I48) between 2010 and 2017. To ensure a cohort of only incident AF, we excluded patients who used any oral anticoagulant during the year before cohort entry as well as patients with a recorded use of warfarin between 2004 and 2006. Patients under 20 years of age were excluded, and patients with permanent migration abroad before 1 January 2019 were excluded, N=157 658. PRIMARY OUTCOME MEASURES: 1-year all-cause, cardiovascular (CV) and cause-specific mortality following AF diagnosis. RESULTS: The study cohort consisted of 157 658 incident AF cases (50.1% male, mean age 72.9 years). Both all-cause and CV mortality declined from cohort entry years 2010-2017 (from 12.9% to 10.6%, mortality rate ratio (MRR) 0.77; 95% CI 0.73 to 0.82 in cohort entry year 2017 with 2010 as reference; and from 7.4% to 5.2%, MRR 0.68; 95% CI 0.63 to 0.74, respectively). Overall mortality and CV mortality were lower in women than in men throughout the study period (MRR 0.66; 95% CI 0.63 to 0.69 and MRR 0.53; 95% CI 0.50 to 0.56, respectively). Deaths attributable to ischaemic heart disease decreased during the study period (from 30.7% to 21.6%, MRR 0.51; 95% CI 0.49 to 0.62 in 2017 vs 2010), whereas dementia and Alzheimer's disease increased as a cause of death over time (6.2% to 9.9%, MRR 1.19; 95% CI 0.96 to 1.48 in 2017 vs 2010). The CHA2DS2-VASc score associated strongly with 1-year survival (p<0.0001). CONCLUSIONS: Our study reiterates that mortality after diagnosis of AF has decreased. The CHA2DS2-VASc score highlights the need to treat comorbidities as it strongly associates with patient 1-year survival after initial AF diagnosis.

Vascular disease and ischemic stroke in patients with atrial fibrillation: Temporal trends and age-related differences.

BACKGROUND AND AIMS: We examined temporal trends and age-related differences in the prevalence of vascular diseases and in their association with ischemic stroke (IS) risk in patients with atrial fibrillation (AF). METHODS: The registry-based FinACAF study covered all patients with AF in Finland during 2007-2018. Incidence rate ratios (IRRs) of IS were computed with Poisson regression, and the interaction of vascular diseases with age and calendar year period was assessed. RESULTS: We identified 229,565 patients (50.0 % female; mean age 72.7 years) with incident AF. The overall prevalence of any vascular disease was 28.6 %, and the prevalence increased from 2007 to 2018, primarily among patients over 75 years. Overall, 5909 (2.6 %) patients experienced IS within the first year after AF diagnosis. Crude IS rate decreased continuously during the study period in both patients with and without vascular diseases, with the rates remaining consistently higher in patients with vascular diseases. Vascular diseases were independently associated with higher IS incidence among patients under 65 years (adjusted IRR with 95 % confidence interval 1.35 (1.10-1.66)), while among older patients, only peripheral artery disease was associated with IS, and other vascular conditions had no association with IS. No interactions between the calendar year period and vascular diseases with IS rate were observed. CONCLUSIONS: The association between vascular diseases and IS has remained stable over time and vascular diseases were independently associated with higher incidence of IS particularly in patients with AF under the age of 65.

Continuity of care and mortality in patients with type 2 diabetes.

BACKGROUND: How continuity of general practitioner care (GP-CoC) affects mortality in patients with type 2 diabetes (T2D) is unclear. AIM: The aim of this study was to examine the effect of having no continuity of care (CoC) and GP-CoC on mortality in primary health care (PHC) patients with T2D. DESIGN & SETTING: Cohort study in patients aged 60 years or older with T2D within the public PHC of the city of Vantaa, Finland. METHOD: Inclusion period was between 2002-2011 and follow-up period between 2011-2018. Six groups were formed (no appointments, one appointment and Modified, Modified Continuity Index [MMCI] quartiles). Mortality was measured with standardized mortality ratio (SMR) and adjusted hazard ratio (aHR). GP-CoC was measured with MMCI. Comorbidity status was determined with Charlson comorbidity index (CCI). RESULTS: In total 11,020 patients were included. Mean follow-up time was 7.3 years. SMRs for the six groups (no appointments, one appointment, MMCI quartiles) were 2.46 (95%CI: 2.24-2.71), 3.55 (3.05-4.14), 1.15 (1.06-1.25), 0.97 (0.89-1.06), 0.92 (0.84-1.01) and 1.21 (1.11-1.31), respectively. With continuous MMCI, mortality formed a u-curve. The inflection point was at a MMCI value of 0.65 with corresponding SMR of 0.86. Age and CCI adjusted HR for death between men and women was 1.45 (1.35-1.58). CONCLUSIONS: Patients with no CoC had the highest mortality. In patients having care over time, the effect of GP-CoC on mortality was minor and mortality turned to rise with high GP-CoC.

Comparing CHA2DS2-VA and CHA2DS2-VASc scores for stroke risk stratification in patients with atrial fibrillation: a temporal trends analysis from the retrospective Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) cohort.

Background: Contemporary data have shown a decrease in the ischaemic stroke risk associated with female sex in patients with atrial fibrillation (AF). We evaluated temporal trends in the predictive value of a non-sex CHA2DS2-VASc risk score (ie. CHA2DS2-VA). Methods: The FinACAF study covers all patients with incident AF between 2007 and 2018 in Finland from all levels of care. The CHA2DS2-VA score was compared with the CHA2DS2-VASc using continuous and category-based net reclassification indices (NRIs), integrated discrimination improvement (IDI), c-statistics and decision curve analyses. Findings: We identified 144,879 anticoagulant naïve patients with new-onset AF between 2007 and 2018 (49.9% women; mean age 72.1 years), of whom 3936 (2.7%) experienced ischaemic stroke during one-year follow-up. Based on both continuous and category-based NRIs, the CHA2DS2-VA score was inferior to the CHA2DS2-VASc in the early years (-0.333 (95% CI -0.411 to -0.261) and -0.118 (95% CI -0.137 to -0.099), respectively). However, the differences attenuated over time, and by the end of the study period, the continuous NRI became non-significant (-0.093 (95% CI -0.165 to 0.032)), whereas the category-based NRI reversed in favor of the CHA2DS2-VA (0.070 (95% CI 0.048-0.087)). The IDI was non-significant in early years (0.0009 (95% CI -0.0024 to 0.0037)), but over time became statistically significant in favor of the CHA2DS2-VA score (0.0022 (95% CI 0.0001-0.0044)). The Cox models fitted with the CHA2DS2-VA and the CHA2DS2-VASc scores exhibited comparable discriminative capability in the beginning of the study (p-value 0.63), but over time marginal differences in favor of the CHA2DS2-VA score emerged (p-value 0.0002). Interpretation: In 2007-2008 (when females had higher AF-related stroke risks than males), the CHA2DS2-VASc score outperformed the CHA2DS2-VA score, but the initial differences between the scores attenuated over time. By the end of the study period in 2017-2018 (with limited/no sex differences in AF-related stroke), there was marginal superiority for the CHA2DS2-VA score. Funding: This work was supported by the Aarne Koskelo Foundation, The Finnish Foundation for Cardiovascular Research, The Finnish State Research funding, and Helsinki and Uusimaa Hospital District research fund.

Prevalence and Factors Associated with Carotid Stenosis in Acute Ischemic Stroke Patients with Atrial Fibrillation.

INTRODUCTION: Among stroke patients with atrial fibrillation (AF), it is not uncommon to identify carotid atherosclerosis. This study aimed to estimate the prevalence of, and factors associated with, carotid atherosclerosis among patients with AF and acute ischemic stroke. PATIENTS AND METHODS: Prospectively collected data from consecutive patients with anterior ischemic stroke and AF who underwent carotid imaging from 10 stroke registries were categorized retrospectively according to the degree of stenosis in: no atherosclerosis, stenosis <50%, stenosis ≥50%, and occlusion. Logistic regression analysis was used to identify factors associated with ipsilateral carotid atherosclerosis. RESULTS: Among 2,955 patients with ischemic stroke and AF, carotid atherosclerosis was evident in 1,022 (34.6%) patients, while carotid stenosis ≥50% and occlusion were identified in 204 (6.9%) and 168 (5.7%) patients, respectively. Ipsilateral carotid stenosis ≥50% or occlusion was associated with higher age (OR: 1.15, 95% CI: 1.01-1.32, per decade), previous ischemic stroke or transient ischemic attack (OR: 1.70, 95% CI: 1.29-2.25), peripheral artery disease (OR: 1.85, 95% CI: 1.23-2.78), coronary artery disease (OR: 1.53, 95% CI: 1.16-2.04), and statin treatment on admission (OR: 1.30, 95% CI: 1.01-1.67). Patients with lacunar stroke had a lower likelihood of stenosis ≥50% or occlusion (OR: 0.29, 95% CI: 0.13-0.68). Compared to the absence of atherosclerotic disease, atherosclerosis in one and two arterial beds was associated with the identification of ipsilateral carotid stenosis (OR: 1.49, 95% CI: 1.22-2.98 and OR: 3.18, 95% CI: 1.85-5.49, respectively). CONCLUSION: Among acute ischemic stroke patients with AF, 1 out of 3 had ipsilateral carotid atherosclerosis, and 1 out of 8 had ipsilateral carotid stenosis ≥50% or occlusion. Atherosclerosis in two arterial beds was the most important predictor for the identification of ipsilateral carotid stenosis. Among ischemic stroke patients with AF, carotid atherosclerosis is common, while carotid imaging should not be overlooked, especially in those with coronary or/and peripheral artery disease.

Comorbidity and Medication Trends in Chronic Kidney Disease and Incident Atrial Fibrillation: A Nationwide Cohort Study.

INTRODUCTION: Chronic kidney disease (CKD) is associated with an 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 <60 mL/min/1.73 m2 was found in 27%, while 318 (0.3%) patients were on dialysis, and 188 (0.2%) had a functioning kidney transplant. Lowering eGFR yielded more comorbidities and medications. During 2010-2018 in patients with eGFR <60 mL/min/1.73 m2 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. CONCLUSION: More than one-fourth of patients with incident AF also had CKD stage 3-5 (eGFR <60 mL/min/1.73 m2). Both comorbidities and medication use increased with worsening kidney function. Prevalence of major cardiovascular (CV) risk factors increased during 2010-2018, but the 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.

Symptomatic diagnoses in primary care: an observational cohort study.

BACKGROUND: Among primary health care patients, it is sometimes impossible to assign a definitive diagnosis for the patient's reported or observed symptoms. Therefore, symptomatic diagnoses are often used. AIM: The aim of the present study was to examine the proportion of symptomatic diagnoses among primary health care patients. We also explored which symptomatic diagnoses were most frequently recorded as well as their age and gender distribution. DESIGN & SETTING: This is a register-based study in the public primary health care of the city of Vantaa, Finland. METHOD: Diagnoses were entered according to the 10th revision of the International Classification of Diseases (ICD-10). The data consisted of every diagnosis entered into the electronic health record between January first 2016 and December 31st 2018. Both absolute numbers and relative proportions of various symptomatic diagnosis recordings (chapter 'R') were reported. RESULTS: Of all the recorded diagnoses (N=503,001), the proportion of R-diagnoses was 13.5% (N=67,905). Diagnoses of symptoms and signs involving the digestive system and abdomen (R10-19) (4.1% of all; n=18,550), the circulatory and respiratory systems (R00-09) (3.9%; n=17,426), general symptoms and signs (R50-69) (3.4%; n=15,165), and the skin and subcutaneous tissue (R20-23) (2.2%; n=9,812) were the most prevalent. Age was also a major factor determining how the symptomatic diagnoses were distributed between women and men. Overall, the symptomatic diagnoses were more common among women than men (14.1% and 12.4%, respectively). The major symptomatic diagnosis categories, including symptoms and signs involving the digestive system and abdomen, the skin and the subcutaneous tissue, and general symptoms and signs, were more predominant among women, while symptoms and signs involving the circulatory and respiratory systems were more common among men. CONCLUSION: A symptomatic diagnosis code was recorded in about one eighth of the GP appointments, although there were significant sex differences in the prevalence within and between diagnosis groups.

Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults.

Background: Incidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be 1 of the underlying mechanisms, but this has only been scarcely explored. Objectives: The purpose of this study was to assess the association between increased LA stiffness and CIS in young adults. Methods: In the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e' velocity (E/e')/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness. Results: Increased LA stiffness was found in 36% of patients and in 18% of controls (P < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders (P = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P < 0.05). Conclusions: LA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages. (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome [SECRETO]; NCT01934725).

Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Thromboembolic and bleeding complications after elective cardioversion of atrial fibrillation: a nationwide cohort study.

AIMS: Elective cardioversion (ECV) is routinely used in atrial fibrillation (AF) to restore sinus rhythm. However, it includes a risk of thromboembolism even during adequate oral anticoagulation treatment. The aim of this study was to evaluate the risk of thromboembolic and bleeding complications after ECV in a real-life setting utilizing data from a large AF population. METHODS AND RESULTS: This nationwide register-based study included all (n = 9625) Finnish AF patients undergoing their first-ever ECV between 2012 and 2018. The thromboembolic and bleeding complications within 30 days after ECV were analysed. The mean age of the patients was 67.7 ± 9.9 years, 61.2% were men, and the mean CHA2DS2-VASc score was 2.6 ± 1.6. Warfarin was used in 6245 (64.9%) and non-vitamin K oral anticoagulants (NOACs) in 3380 (35.1%) cardioversions. Fifty-two (0.5%) thromboembolic complications occurred, of which 62% were ischaemic strokes, 25% transient ischaemic attacks, and 13% other systemic embolisms. Thromboembolic events occurred in 14 (0.4%) NOAC-treated patients and in 38 (0.6%) warfarin-treated patients (odds ratio 0.77; confidence interval: 0.42-1.39). The median time from ECV to the thromboembolic event was 2 days, and 78% of the events occurred within 10 days. Age and alcohol abuse were significant predictors of thromboembolic events. Among warfarin users, thromboembolic complications were more common with international normalized ratio (INR) <2.5 than INR ≥2.5 (0.9% vs. 0.4%, P = 0.026). Overall, 27 (0.3%) bleeding events occurred. CONCLUSION: The rate of thromboembolic and bleeding complications related to ECV was low without significant difference between NOAC- and warfarin-treated patients. With warfarin, INR ≥2.5 at the time of cardioversion reduced the risk of thromboembolic complications.

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.

Who visits primary health care general practitioners and why? A register-based study in a Finnish city.

This is a register-based study that examines the distribution of diagnoses made by general practitioners (GPs) in the public primary health care of the city of Vantaa, Finland. Data were gathered from the electronic health record (EHR) system and consisted of every record entered into the EHR system between 1 January 2016 and 31 December 2018. Both absolute numbers and relative proportions of the 10th edition of International Classification of Diseases (ICD-10) diagnosis recordings were reported and calculated. Among GP visits, the 88 most common diagnoses covered 75% of all diagnoses. The most common diagnoses were related to the musculoskeletal (3.8%, ICD code M54) and respiratory systems (6.0%, ICD-10 code J06). Primary health care GP services were mostly used by children (age <5 years) and older adults (>65 years). Health examinations - mostly children's and maternity clinics appointments/visits - covered 20% of the GP office visits. Women between the ages 15-79 years had relatively more GP visits compared to men. The 88 most commonly recorded diagnoses covered the majority of the GP visits. Health examinations for the healthy were an important part of GPs' work. In an urban Finnish city, GP services were predominantly used by children and older adults.

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.

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

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.

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.

Associations of anaemia with bleeding and thrombotic complications in patients with atrial fibrillation treated with warfarin: a registry-based nested case-control study.

OBJECTIVES: We studied association of laboratory testing beyond the international normalised ratio (INR) with bleeding and stroke/transient ischaemic attack (TIA) outcomes in patients with atrial fibrillation treated with warfarin. DESIGN: This was a retrospective nested case-control study from the Finnish Warfarin in Atrial Fibrillation (FinWAF) registry (n=54 568), reporting the management and outcome in warfarin-anticoagulated patients. Associations of blood count test frequency and results were assessed together with risk of bleeding or stroke/TIA during 5-year follow-up. SETTING: National FinWAF registry, with data from all six hospital districts. Follow-up period for complications was 1 January 2007-31 December 2011. PARTICIPANTS: A total of 54 568 warfarin-anticoagulated patients. RESULTS: The number of patients with bleeding was 4681 (9%) and stroke/TIA episodes, 4692 (9%). In patients with bleeds, lower haemoglobin (within 3 months) preceded the event compared with the controls (median 126 vs 135 g/L; IQR 111-141 g/L vs 123-147 g/L, p<0.001), while patients with stroke/TIA had only modestly lower INR (median 2.2 vs 2.3; 1.8-2.6 vs 2.1-2.7, p<0.001). When the last measured haemoglobin was below the reference value (130 g/L for men, 120 g/L for women), the OR for a bleeding complication was 2.9 and stroke/TIA, 1.5. If the haemoglobin level was below 100 g/L, the complication risk increased further by 10-fold. If haemoglobin values were repeatedly (more than five times) low during the preceding 3 months, future OR was for bleeds 2.3 and for stroke/TIA 2.4. CONCLUSIONS: The deeper the anaemia, the higher the risk of bleeding and stroke/TIA. However, INR remained mainly at its target and only occasionally deviated, failing to detect the complication risk. Repeated low haemoglobin results, compatible with persistent anaemia, refer to suboptimal management and increased the complication risk in anticoagulated patients.

Trends and burden of diabetes in patients with atrial fibrillation during 2007-2018: A Finnish nationwide cohort study.

AIMS: We assessed the temporal trends in the prevalence of diabetes and in its associations with outcomes among patients with atrial fibrillation (AF). METHODS: The registry-based FinACAF study covered all patients with incident AF in Finland between 2007 and 2018. Ischemic stroke (IS) and mortality rates were computed using Poisson regression model. RESULTS: We identified 229565 patients (50.0% female; mean age 72.7 years; mean follow-up 4.0 years) patients with incident AF. The prevalence of diabetes increased steadily from 15.5% in 2007 to 26.3% in 2018. A decrease in IS and mortality rates was observed during the study period both in patients with and without diabetes. Diabetes was associated with IS and mortality (adjusted incidence rate ratios with 95% confidence intervals 1.22 (1.17-1.26) and 1.32 (1.29-1.34), respectively). The impact of diabetes on IS risk remained stable, while its effect on mortality increased slightly during the observation period. CONCLUSIONS: The prevalence of diabetes has increased considerably among patients with AF between 2007 and 2018. There have been substantial improvements in the prognosis of AF patients with diabetes. However, diabetes remains a significant risk factor for IS and mortality in this patient population.