Miika Linna

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.

No data exist on whether ischemic stroke admissions among patients with atrial fibrillation (AF) vary by day of the week. The nationwide registry-linkage FinACAF study includes all patients with incident AF in Finland between 2007 and 2018. This analysis focused on patients who experienced their first-ever ischemic stroke. Hospital stroke admissions were categorized by day of the week, and a weekday-to-weekend ratio was calculated as the ratio of strokes on a weekday versus a weekend day. We identified 13 781 patients (mean age 79.2 years; 57.1% women) with AF admitted for ischemic stroke. Stroke admissions varied significantly by day of the week (p < 0.001), with the highest number occurring on Mondays (16.1% of all strokes), followed by a progressive decline over the week. Admission rates were notably higher on Monday and Tuesday, remained relatively stable from Wednesday to Friday, and decreased on Saturday and Sunday (11-12% of all strokes per day). The overall weekday-to-weekend ratio was 1.31 (95% CI 1.26-1.37) and was more pronounced in men than in women, as well as during the first half of the study period (2007-2012) compared to the latter half (2013-2018). This nationwide cohort study demonstrates a clear day-of-the-week variation in hospital admissions for ischemic stroke among patients with AF, with fewer admissions on weekends than on weekdays. Promoting awareness of stroke symptoms and the importance of seeking timely care regardless of the day may represent a modifiable target to improve outcomes in patients with AF who experience stroke.

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.

Aims: Little is known about the association of venous thromboembolisms (VTEs) on the risk of ischaemic stroke (IS) in patients with atrial fibrillation (AF). Nevertheless, both pulmonary embolism (PE) and deep venous thromboembolism (DVT) are often included in the calculation of the CHA2DS2-VASc score, which is used for stroke risk stratification. Therefore, we conducted this nationwide retrospective cohort study to evaluate whether a history of VTE is associated with an increased risk of IS in patients with AF. Methods and results: The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) registry-linkage study includes all patients in Finland with incident AF from 2007 to 2018. The IS rates and rate ratios were computed for patients with and without a history of VTE. We identified 271 500 patients with new-onset AF, of whom 4.6% had prior VTE, while 1.9% had a history of PE and 3.1% a history of DVT. The crude incidence of IS was slightly higher in patients with a history of VTE compared to patients without a history of VTE, but after adjusting for baseline factors, VTE was not associated with the rate of IS [adjusted incidence rate ratio with 95% confidence interval for any VTE 1.05 (0.98–1.13), for PE 1.01 (0.91–1.13), and for DVT 1.09 (1.00–1.18)]. There was no temporal change in these associations during the study period. Conclusion: A history of VTEs was not associated with an increased risk of IS, suggesting that they do not need to be considered in the stroke risk stratification of patients with AF.

Aims: Direct oral anticoagulants (DOACs) at reduced dosage regimens are the first choice of ischaemic stroke (IS) prevention for patients with atrial fibrillation (AF) and elevated bleeding risk or renal insufficiency. We compared the outcomes of reduced dose DOACs and warfarin. Methods and results: We included all new-onset patients with AF in Finland from 2011 to 2018. Adjusted hazard ratios (HRs) for IS, intracranial haemorrhage (ICH), bleeding, and mortality were calculated for dabigatran (n = 2 672), rivaroxaban (n = 1 866), apixaban (n = 3 936), and warfarin (n = 43 548). Patients on warfarin were grouped into quartiles by their individual time-in-therapeutic range (TTR), with the second best TTR quartile as a reference group for comparisons. Risk of IS was highest in the low TTR quartiles of warfarin, lowest in the best TTR quartile (0.65 95% confidence interval, 0.51–0.83), and did not differ for dabigatran, rivaroxaban, and apixaban compared with the second best TTR quartile. Risk of ICH was highest in low TTR quartiles of warfarin (HRs 7.20, 5.48–9.46 and 1.91, 1.44–2.55), and was not different in patients on dabigatran, rivaroxaban, and apixaban. Risk of all-cause death and bleeding were lowest in the two best TTR quartiles, and highest in the poorest TTR group. Mortality was higher for dabigatran, rivaroxaban, and apixaban, compared with the second best TTR quartile of warfarin. Conclusion: DOACs with reduced doses are efficient and safe stroke prevention therapy in high-risk patients with AF when compared with warfarin therapy of sufficient TTR. In this comparison, warfarin therapy of excellent TTR-quality was associated with the lowest risk of bleeding and mortality.

BackgroundPatients with atrial fibrillation (AF) are often treated with antiarrhythmic drugs (AADs) to maintain sinus rhythm and with heart rate-lowering drugs to achieve optimal rate control. In this study we investigated trends in the use of AADs and rate control drugs in Finnish patients with AF.Methods and resultsThe Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study is a nationwide study including all patients with AF in Finland from 2007 to 2018. The number of AAD purchases and the proportions of all prevalent AF patients in a certain year of interest were calculated.In total, 391030 AF patients were identified between 2007 and 2018, and 39816 (10.2%) of them had purchased either class I or III AADs. The proportion of patients using class I and III AADs decreased from 8.6% to 6.3%. Flecainide and amiodarone were the most often used AADs. The use of flecainide and amiodarone decreased from 4.9% to 3.9% and 1.9% to 1.5%, respectively. The proportion of patients on beta-blockers remained stable at 75%. Dronedarone became available in 2011 when it also was the most used (0.8% of patients), but the use decreased thereafter. The use of sotalol and digoxin decreased from 1.5% to 0.6% and 24.6% to 11.0% over the study period.ConclusionThe number of AAD purchases increased alongside with the increasing prevalence of AF, whereas the proportion of AF patients on class I and III AADs and digoxin decreased between 2007 and 2018. Flecainide remained the most used AAD followed by amiodarone.