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.

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 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.

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.

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.

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.

The nationwide Finnish anticoagulation in atrial fibrillation (FinACAF): study rationale, design, and patient characteristics.

Atrial fibrillation (AF) is a major cause of ischemic stroke and the number of AF patients is increasing. Thus, up-to-date multifaceted data about the characteristics of AF patients, their treatments, and outcomes are urgently needed. The Finnish anticoagulation in atrial fibrillation (FinACAF) study has collected comprehensive data on all Finnish AF patients from 1st January 2004 to 31st December 2018. The aim of this paper is to describe the study rationale, the process of integrating data from the applied resources and to define the study cohort. Using national unique personal identification number, individual patient data is linked from nationwide health care registries (primary, secondary, and tertiary care), drug purchases, education, and socio-economic status as well as places of domicile, incomes, and taxes. Six regional laboratory databases (~ 282,000, 77% of the patients) are also included. The study cohort comprises of a total of 411,000 patients. Since the introduction of the national primary care register in 2012, 9% of all AF patients were identified outside hospital care registers. The prevalence of AF in Finland-4.1% of whole population-is for the first time now established. The FinACAF study allows a unique possibility to investigate the epidemiology and socio-medico-economic impact of AF as well as the cost effectiveness of different AF management strategies in a completely unselected, nationwide population. This article provides the rationale and design of the study together with a summary of the characteristics of the cohort.