Aapo L. Aro

Background and ObjectivesPatients with atrial fibrillation (AF) and previous intracranial bleeding are at high risk of ischemic and bleeding events, and the benefits and risks of oral anticoagulati...

Background and Aims: Previous literature has suggested that the risk of ischaemic stroke (IS) is lower in patients with atrial flutter (AFL) compared with patients with atrial fibrillation (AF), but large-scale studies with electrocardiogram (ECG) documentation are not available. Methods: The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation study included all patients with AF and AFL in Finland from 2007 to 2018. Based on the digitally recorded ECGs, patients were categorized into AF-only, AFL-only, or combined AF and AFL groups. IS rates and adjusted incidence rate ratios (IRRs) were calculated. Results: A total of 40 986 patients with new-onset AF/AFL and 532 041 digitally documented ECGs were identified. The AF-only group included 30 261 patients (48.2% women, mean age 71.8 years), the AFL-only group 2409 patients (38.8% women, mean age 70.8 years), and the AF & AFL group 8316 patients (53.9% women, mean age 72.4 years). Of these, 31 795 (77.6%) initiated anticoagulation during a mean follow-up of 1.2 years. Overall, IS was observed in 3165 (7.7%) patients. The crude rate of IS was highest in the AF & AFL group [2.1 per 100 patient-years, 95% confidence interval (CI) 1.9–2.2] compared to the AF-only group (1.9 per 100 patient-years, 95% CI 1.8–1.9) and AFL-only group (1.1 per 100 patient-years, 95% CI 0.9–1.3). Adjusted IRR of IS was lower in the AFL-only group (0.60, 95% CI 0.49–0.74) and slightly higher in the AF & AFL group (1.11, 95% CI 1.02–1.20) compared with patients with AF-only. These findings were consistent in analyses restricted to follow-up time without anticoagulation and before catheter ablation, as well as across CHA2DS2-VA score categories. Conclusions: In this large cohort of patients, those with AFL-only had a substantially lower risk of IS than patients with AF-only, suggesting clinically meaningful differences in thromboembolic risk between these arrhythmias.

Aims: To evaluate the association of HbA1c level at the time of atrial fibrillation (AF) diagnosis with adverse outcomes (death, ischemic stroke (IS), myocardial infarction (MI), bleeding) in an unselected nationwide cohort of patients with AF and diabetes mellitus (DM). Methods: The retrospective FinACAF registry study covered all patients with incident AF in Finland between 2010 and 2017. Outcomes were analyzed using HRs and sHRs (hazard ratios and subdistribution hazard ratios), with HbA1c modelled both categorically and continuously. Results: Among 157 658 patients with incident AF, DM was present in 23% (n = 35 872). Baseline HbA1c was available in 49% (17 519) of DM patients. DM was associated with increased hazards of all evaluated outcomes. Elevated HbA1c in categorical analyses was associated with progressively increased adjusted HRs and sHRs, with highest ratios seen in HbA1c > 63 mmol/mol for death (HR 1.56, 95% CI 1.45–1.68), IS (sHR 1.38 95% CI 1.20–1.59), and MI (sHR 1.70 95% CI 1.48–1.94), when compared to patients without DM. In continuous analyses, higher HbA1c levels were associated with increasing hazards for mortality, IS, and MI. Bleeding hazards remained stable across the HbA1c spectrum. Conclusions: Higher baseline HbA1c levels were associated with progressively increased hazards of mortality, IS, and MI in patients with incident AF and DM.

BACKGROUND: Gout is an emerging cardiovascular risk factor. We aimed to assess whether gout is associated with an increased risk of stroke in patients with atrial fibrillation (AF). METHODS: The nationwide registry-linkage FinACAF study (Finnish Anticoagulation in Atrial Fibrillation) included all patients with AF in Finland between 2007 and 2018 from all levels of care. Based on diagnosis codes and pharmacy claims data, the association of gout and urate-lowering therapy with the incidence of ischemic stroke was assessed. RESULTS: We identified 229 565 patients with new-onset AF (50.0% female; mean age, 72.7 years; mean follow-up, 4.0 years), of whom 6 910 (3.0%) had a history of gout. A total of 16 296 (7.1%) patients experienced an ischemic stroke. Gout was associated with higher stroke rates in both unadjusted and adjusted analyses (incidence rate ratio, 1.35 [95% CI, 1.22–1.49] and incidence rate ratio, 1.12 [95% CI, 1.02–1.24], respectively). Analyses restricted to follow-up without anticoagulation yielded consistent results with slightly higher point estimates (incidence rate ratio, 1.88 [95% CI, 1.63–2.17] unadjusted; incidence rate ratio 1.26 [95% CI, 1.09–1.46] adjusted). In patients with gout and AF, time-dependent exposure to urate-lowering therapy was associated with a 30% lower stroke rate. Nonanticoagulated crude stroke rates were 1.5, 1.0, and 4.8 per 100 patient-years for gout patients with CHA ₂ DS ₂ -VA scores of 0, 1, and ≥2, respectively. CONCLUSIONS: Gout is an important risk factor for ischemic stroke in patients with AF, and considering gout could improve stroke risk stratification. Urate-lowering therapy was associated with reduced stroke risk, suggesting that gout is a modifiable risk factor in patients with AF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04645537.

Background: Limited data exist on characteristics and patterns associated with patients with atrial fibrillation (AF) who encounter first-ever ischemic stroke (IS) while not on oral anticoagulation (OAC) therapy. Methods: From a nationwide registry-linkage database including all patients with AF in Finland from 2007 to 2017, we included those with IS after diagnosis of AF and those without IS. Factors associated with non-OAC use among IS patients were examined using logistic regression, with separate models for independent variables and risk scores. Results: Among 174,094 patients with new-onset AF, 11,680 (6.7%) patients (56.9% female; mean age 79.0 years) experienced IS. A total of 7507 (64.3%) of IS patients were not on OAC at the time of IS (mean age 78.9 years; 57.2% female). The proportion of non-OAC decreased from 77.2% to 45.6% over the study period. In the adjusted logistic regression model, the strongest factor associated with non-OAC was CHA2DS2-VA score of 0 points (OR 4.561; 95% CI, 3.097–6.718), followed by a score of 1 point (OR 2.382; 95% CI, 1.971–2.879). Other significant independent factors associated with non-OAC use were alcohol abuse (OR 2.282; 95% CI, 1.805–2.885), liver dysfunction (OR 2.120; 95% CI, 1.335–3.367), renal dysfunction (OR 1.430; 95% CI, 1.200–1.703), dementia (OR 1.394; 95% CI, 1.227–1.583), prior myocardial infarction (OR 1.346; 95% CI, 1.181–1.535), age <65 years (OR 1.274; 95% CI, 1.034–1.571), lowest income (OR 1.232; 95% CI, 1.104–1.374), female sex (OR 1.177; 95% CI, 1.077–1.287), and antiplatelets/NSAID use (OR 1.133; 95% CI, 1.042–1.231). Conclusions: Less than 2% of AF patients experienced IS during study period and among these around 63% were without appropriate OAC therapy at the time of the IS. However, decreasing trend of non-OAC use was identified throughout the study period.

Patients with atrial fibrillation (AF) undergoing cardioversion (CV) are exposed to increased risk of ischaemic stroke (IS), but the exact magnitude is unknown. We compared IS rates during the post-CV period with the long-term risk in AF patients using guideline-recommended anticoagulation therapy. This nationwide register-based study included all AF patients undergoing first-ever elective CV between 2012 and 2018 in Finland. Breakpoint analysis identified a cut-off point in the IS rate at 2 weeks after CV. Follow-up was split into two intervals: the immediate 2-week post-CV period and the subsequent period up to 360 days. Stroke rates were calculated, and incidence rate ratios were estimated with Poisson regression. Interactions between the two follow-up periods and conventional IS risk factors as well as anticoagulation treatment were assessed. A total of 9625 patients were identified (mean age 67.7 ± 9.9 years, 61.2% men, mean CHA2DS2-VA score 2.2 ± 1.4). Warfarin was used in 6245 (64.9%) and non-vitamin K oral anticoagulants in 3380 (35.1%) patients. Overall, 92 (1.0%) patients experienced IS during the year after CV. Breakpoint analysis and survival plot displayed a higher incidence of IS within the first 2 weeks after CV, stabilizing thereafter to a consistent level. The adjusted IS rate during the first 2 weeks was 7.5-fold (95% confidence interval: 4.8-11.8) compared to the subsequent IS rate. This excess risk was independent of the anticoagulation type or conventional stroke risk factors. The rate of IS was roughly seven times higher during the first 2 weeks after elective CV compared to the subsequent 360 days.

Background The cost burden of new-onset atrial fibrillation (AF) has not previously been studied with unselected nationwide data. Objective We analyzed differences in the distribution and time course of costs from all categories of healthcare services in patients receiving direct oral anticoagulants (DOACs), warfarin, or no anticoagulation during the first year following diagnosis of AF. Methods This sub-study of the Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) project comprised all new-onset AF patients from 2011 to 2017 in Finland with an indication for oral anticoagulation treatment. The registry data included information on primary and secondary care services as well as social care services, drug purchases, laboratory data, and reimbursed private care and travel services. We report inverse probability of treatment weighted average costs for different pharmaceutical groups with bootstrapped confidence intervals. Results In total, 130,745 patients (66,610 on warfarin, 32,996 on DOACs) were included. Weighted first-year costs after onset of AF were €11,364 for rivaroxaban (n = 13,230), €12,642 for apixaban (n = 11,886), €11,403 for dabigatran (n = 7514), and €10,752 for edoxaban (n = 366). Costs were clustered near the diagnosis of AF. Costs for warfarin patients were inversely related to the quality of anticoagulation therapy. Average first-year costs for warfarin patients were €15,860, higher than for patients on DOACs by €3218–€5108. Patients without any oral anticoagulation had the highest first-year costs, €17,682. Patients with high risk of stroke had higher total costs, both in patients using DOACs and warfarin. Conclusions DOACs had lower total costs than warfarin despite higher drug expenses. Patients without any oral anticoagulation had the highest costs. ClinicalTrials Identifier NCT04645537. ENCePP Identifier EUPAS29845.

Background: Limited data exist on characteristics and patterns associated with patients with atrial fibrillation (AF) who encounter first-ever ischemic stroke (IS) while not on oral anticoagulation (OAC) therapy. Methods: From a nationwide registry-linkage database including all patients with AF in Finland from 2007 to 2017, we included those with IS after diagnosis of AF and those without IS. Factors associated with non-OAC use among IS patients were examined using logistic regression, with separate models for independent variables and risk scores. Results: Among 174,094 patients with new-onset AF, 11,680 (6.7%) patients (56.9% female; mean age 79.0 years) experienced IS. A total of 7507 (64.3%) of IS patients were not on OAC at the time of IS (mean age 78.9 years; 57.2% female). The proportion of non-OAC decreased from 77.2% to 45.6% over the study period. In the adjusted logistic regression model, the strongest factor associated with non-OAC was CHA ₂ DS ₂ -VA score of 0 points (OR 4.561; 95% CI, 3.097–6.718), followed by a score of 1 point (OR 2.382; 95% CI, 1.971–2.879). Other significant independent factors associated with non-OAC use were alcohol abuse (OR 2.282; 95% CI, 1.805–2.885), liver dysfunction (OR 2.120; 95% CI, 1.335–3.367), renal dysfunction (OR 1.430; 95% CI, 1.200–1.703), dementia (OR 1.394; 95% CI, 1.227–1.583), prior myocardial infarction (OR 1.346; 95% CI, 1.181–1.535), age <65 years (OR 1.274; 95% CI, 1.034–1.571), lowest income (OR 1.232; 95% CI, 1.104–1.374), female sex (OR 1.177; 95% CI, 1.077–1.287), and antiplatelets/NSAID use (OR 1.133; 95% CI, 1.042–1.231). Conclusions: Less than 2% of AF patients experienced IS during study period and among these around 63% were without appropriate OAC therapy at the time of the IS. However, decreasing trend of non-OAC use was identified throughout the study period.