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.

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.

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.

Rural-urban differences in the initiation of oral anticoagulant therapy in patients with incident atrial fibrillation: A Finnish nationwide cohort study.

AIMS: Little is known about rural-urban differences in the treatment and outcomes in patients with atrial fibrillation (AF). We aimed to assess whether the initiation of oral anticoagulant (OAC) therapy in patients with AF differs between those with rural and urban residence. METHODS: The registry-based FinACAF cohort covers all patients with AF from all levels of care in Finland. Patients were divided into rural and urban categories and into urbanization degree tertiles based on their municipality of residence at the time of AF diagnosis. The outcome was the first redeemed OAC prescription. RESULTS: We identified 222 419 patients (50.1% female; mean age 72.8 (SD 13.2) years) with incident AF during 2007-2018. Urban residence was associated with a lower rate of OAC therapy initiation (adjusted subdistribution hazard ratio (SHR) (95% CI) 0.96 (0.95-0.97)). Correspondingly, an inverse graded dose-response relationship was observed between higher urbanization degree tertile and OAC initiation rate (highest tertile compared to lowest: adjusted SHR (95% CI) 0.94 (0.93-0.95)). The adoption of direct oral anticoagulants for stroke prevention was faster among patients with urban residence. CONCLUSION: This nationwide cohort study documented that urban residence is associated with a slightly lower rate of OAC therapy initiation in patients with incident AF, but faster adoption of direct oral anticoagulant use.

Rural-Urban differences in Use of Rhythm Control Therapies in Patients with Incident Atrial Fibrillation: A Finnish Nationwide Cohort Study.

Background: Rural-urban disparities have been reported in the access, utilization, and quality of healthcare. We aimed to assess whether use of antiarrhythmic therapies (AATs) in patients with atrial fibrillation (AF) differs between those with rural and urban residence. Methods: The registry-based FinACAF cohort covers all patients with AF from all levels of care in Finland. Patients were divided into rural and urban categories and into urbanization degree tertiles based on their municipality of residence at the time of AF diagnosis. The primary outcome was the use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription. Results: We identified 177,529 patients (49.9% female, mean age 73.0 (SD13.0) years) with incident AF during 2010-2018. Except for AADs, the differences in AAT use were nonsignificant when patients were stratified according to the rural-urban classification system (urban vs. rural adjusted incidence rate ratios (aIRRs) with 95% CIs for any AAT 1.01 (0.99-1.03), AADs 1.11 (1.07-1.15), cardioversion 1.01 (0.98-1.03), catheter ablation 1.05 (0.98-1.12)). However, slightly higher use of all rhythm control modalities was observed in the highest urbanization degree tertile when compared to the lowest tertile (aIRRs with 95% Cis for any AAT 1.06 (1.03-1.08), AADs 1.18 (1.14-1.23), cardioversion 1.05 (1.02-1.08), catheter ablation 1.10 (1.02-1.19)). Conclusions: This nationwide retrospective cohort study observed that urban residence is associated with higher use of AADs in patients with incident AF. Otherwise, the observed disparities were only marginal, suggesting that in the use of rhythm control therapies, no large rural-urban inequity exists in Finland.

Mental health conditions and use of rhythm control therapies in patients with atrial fibrillation: a nationwide cohort study.

OBJECTIVES: Mental health conditions (MHCs) have been associated with undertreatment of unrelated medical conditions, but whether patients with MHCs face disparities in receiving rhythm control therapies for atrial fibrillation (AF) is currently unknown. We assessed the hypothesis that MHCs are associated with a lower use of antiarrhythmic therapies (AATs). DESIGN: A nationwide retrospective registry-based cohort study. SETTING: The Finnish AntiCoagulation in Atrial Fibrillation cohort included records on all patients with AF in Finland during 2007-2018 identified from nationwide registries covering all levels of care as well as drug purchases. MHCs of interest were diagnosed depression, bipolar disorder, anxiety disorder, schizophrenia and any MHC. PARTICIPANTS: We identified 239 222 patients (mean age 72.6±13.2 years; 49.8% women) with incident AF, in whom the prevalence of any MHC was 19.9%. OUTCOMES: Primary outcome was use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription. RESULTS: Lower overall use of any AAT emerged in patients with any MHC than in those without MHC (16.9% vs 22.9%, p<0.001). Any MHC, depression, bipolar disorder, anxiety disorder and schizophrenia were all associated with lower incidence of any AAT with adjusted subdistribution HRs of 0.790 (95% CI 0.771 to 0.809), 0.817 (0.796 to 0.838), 0.811 (0.789 to 0.835), 0.807 (0.785 to 0.830) and 0.795 (0.773 to 0.818), respectively. Adjusted rates of AAD, cardioversion and catheter ablation use were lower in all MHC groups compared with patients without MHC. The findings in patients with any MHC were confirmed in propensity score matching analysis. CONCLUSIONS: Among patients with AF, a clear disparity exists in AAT use between those with and without MHCs. TRIAL REGISTRATION NUMBER: ClinicalTrials Identifier: NCT04645537; ENCePP Identifier: EUPAS29845.

Socioeconomic disparities in use of rhythm control therapies in patients with incident atrial fibrillation: A Finnish nationwide cohort study.

Background: In patients with atrial fibrillation (AF), socioeconomic disparities have been reported in the use of oral anticoagulant therapy and outcomes, but whether income also affects the utilization of antiarrhythmic therapies (AATs) for rhythm control is unknown. We assessed the hypothesis that AF patients with higher income are more likely to receive AATs. Methods: The nationwide retrospective registry based FinACAF cohort study covers all patients with AF from all levels of care in Finland. Patients were divided in AF diagnosis year and age-group specific income quintiles according to their highest annual income during 2004-2018. The primary outcome was the use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription. Results: We identified 188 175 patients (mean age 72.6 ± 13.0 years; 49.6% female) with incident AF during 2010-2018. Patients in higher income quintiles had consistently higher use of all AAT modalities. When compared to patients in the lowest income quintile, the adjusted incidence rate ratios (95% CI) in the highest quintile were 1.53 (1.48-1.59) for any AAT, 1.71 (1.61-1.81) for AADs, 1.43 (1.37-1.49) for cardioversion, and 2.00 (1.76-2.27) for catheter ablation. No temporal change during study period was observed in the magnitude of income disparities in AAT use, except for a decrease in income-related differences in the use of AADs. Conclusion: Profound income-related disparities exist in AAT use among patients with AF in Finland, especially in the use catheter ablation.

Mental Health Conditions and Nonpersistence of Direct Oral Anticoagulant Use in Patients With Incident Atrial Fibrillation: A Nationwide Cohort Study.

Background Mental health conditions (MHCs) are associated with poor outcomes in patients with atrial fibrillation. However, persistence of oral anticoagulation therapy in patients with atrial fibrillation and MHCs is unknown. We aimed to evaluate the effect of MHCs on the persistence of direct oral anticoagulant (DOAC) use in patients with atrial fibrillation based on a nationwide cohort. Methods and Results The nationwide registry-based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) cohort included 67 503 patients with incident atrial fibrillation and indication for permanent oral anticoagulation (CHA2DS2-VASc score >1 in men and >2 in women) starting DOAC therapy between 2011 and 2018. MHCs of interest were depression, bipolar disorder, anxiety disorder, schizophrenia, and composite of any MHC. The main outcome was nonpersistence of DOAC use, defined as the first 120-day period without DOAC purchases after drug initiation. The mean age of the patients was 75.3±8.9 years, 53.6% were women, and the prevalence of any MHC was 17.8%. Persistence after 1 year from DOAC initiation was 79.3% in patients without MHCs and 77.2% in patients with any MHC, and after 2 years were 64.4% and 60.6%, respectively (P<0.001). Higher incidence of nonpersistence to DOACs was observed in all MHC categories: adjusted subdistribution hazard ratios, 1.16 (95% CI, 1.11-1.21) for any MHC, 1.32 (95% CI, 1.22-1.42) for depression, 1.44 (95% CI, 1.15-1.80) for bipolar disorder, 1.25 (95% CI, 1.11-1.41) for anxiety disorder, and 1.30 (95% CI, 1.02-1.64) for schizophrenia. However, patients with only anxiety disorder without other MHCs were not at higher risk of nonpersistence. Conclusions MHCs are associated with nonpersistence of DOAC use. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537.

Mental health conditions and adherence to direct oral anticoagulants in patients with incident atrial fibrillation: A nationwide cohort study.

OBJECTIVE: Medication adherence is essential for effective stroke prevention in patients with atrial fibrillation (AF). We aimed to assess whether adherence to direct oral anticoagulants (DOACs) in AF patients is affected by the presence of mental health conditions (MHCs). METHODS: The nationwide FinACAF cohort covered 74,222 AF patients from all levels of care receiving DOACs during 2011-2018 in Finland. Medication possession ratio (MPR) was used to quantify adherence. Patients with MPR ≥0.90 were defined adherent. MHCs of interest were depression, bipolar disorder, anxiety disorder and schizophrenia. RESULTS: The patients' (mean age 75.4 ± 9.5 years, 50.8% female) mean MPR was 0.84 (SD 0.22), and 59.5% had MPR ≥0.90. Compared to patients without MHC, the adjusted ORs (95% CI) for adherent DOAC use emerged slightly lower in patients with depression (0.92 (0.84-0.99)) and bipolar disorder (0.77 (0.61-0.97)) and unsignificant in patients with anxiety disorder (1.08 (0.96-1.21)) and schizophrenia (1.13 (0.90-1.43)). However, when only persistent DOAC therapy was analyzed, no MHC was associated with poor adherence, and instead anxiety disorder was associated with adherent DOAC use (1.18 (1.04-1.34)). CONCLUSION: Adherence to DOACs in AF patients in Finland was relatively high, and no meaningful differences between patients with and without MHCs were observed.