Intermediate Risk Of Stroke Research Articles

Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study.

The benefit of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) and intermediate stroke risk is debated. In a nationwide Norwegian cohort with a non-sex CHA2DS2-VASc risk score of one, this study aimed to investigate (i) stroke and bleeding risk in AF patients with and without OAC treatment, and (ii) the risk of stroke in non-anticoagulated individuals with and without AF. A total of 1 118 762 individuals including 34 460 AF patients were followed during 2011-18 until ischaemic stroke, intracranial haemorrhage, increased CHA2DS2-VASc score, or study end. One-year incidence rates (IRs) were calculated as events per 100 person-years (%/py). Cox regression models provided adjusted hazard ratios (aHRs [95% confidence intervals]). Among AF patients, the ischaemic stroke IR was 0.51%/py in OAC users and 1.05%/py in non-users (aHR 0.47 [0.37-0.59]). Intracranial haemorrhage IR was 0.28%/py in OAC users and 0.19%/py in non-users (aHR 1.23 [0.88-1.72]). Oral anticoagulant use was associated with an increased risk of major bleeding (aHR 1.37 [1.16-1.63]) but lower risk of the combined outcome of ischaemic stroke, major bleeding, and mortality (aHR 0.57 [0.51-0.63]). Non-anticoagulated individuals with AF had higher risk of ischaemic stroke compared to non-AF individuals with the same risk profile (aHR 2.47 [2.17-2.81]). In AF patients at intermediate risk of stroke, OAC use was associated with overall favourable clinical outcomes. Non-anticoagulated AF patients had higher risk of ischaemic stroke compared to the general population without AF with the same risk profile.

Atrial fibrillation patients at intermediate risk of stroke rapidly progress to high stroke risk: A nationwide registry study (AFNOR)

Abstract Background Stroke risk according to the CHA2DS2-VASc score guides oral anticoagulant (OAC) treatment in atrial fibrillation (AF) patients, and OAC is strongly recommended in patients with high stroke risk. There is less evidence of the clinical benefit of OAC in intermediate risk patients (non-sex CHA2DS2-VASc score of 1), and according to guidelines, OAC should be considered. However, the stroke risk is dynamic and an increase in the CHA2DS2-VASc score with a consequent change in the thromboembolic risk profile favoring OAC treatment is expected over time. Purpose To investigate the temporal changes in CHA2DS2-VASc score and the incidence of acquiring each of the CHA2DS2-VASc risk factors in AF patients at intermediate risk of stroke. Methods We identified 27,111 individuals with non-valvular AF aged ≥18 years, with a baseline CHA2DS2-VASc score of 1 (males) or 2 (females), in data from Norwegian national registries from 2011 through 2018. AF and stroke risk factors were identified with a minimum three-year look-back period. Individuals entered the study upon registration of a first-time AF diagnosis in combination with the first non-sex CHA2DS2-VASc risk factor, whichever came last. All participants were followed until an increase in the CHA2DS2-VASc score, death, emigration or study end. We calculated time from entry to an increased score (non-sex CHA2DS2-VASc score of ≥2) and assessed the cumulative proportions with an increase in CHA2DS2-VASc score per month. Average annual incidence rates for acquirement of new stroke risk factors were calculated as cases per 100 person-years (%/year) with 95% confidence intervals (CI). Results During a median follow-up time of 16 months (interquartile range: 4.9-36.6), 15,397 (56.8%) patients acquired at least one new stroke risk factor(s) (figure 1). One third of the patients who increased their CHA2DS2-VASc score, attained a new risk factor during the first four months of follow-up. The average annual risk of CHA2DS2-VASc score increment was 29% (95% CI: 28.6-29.5). The annual risk for a new risk factor was 23.2% for hypertension, 12.5% for age 65-74 years, 7.9% for heart failure, 6.2% for age ≥ 75 years, 5.4% for vascular disease, 2.4% for diabetes mellitus and 1.6% for thromboembolism (ischemic stroke, transitoric ischemic attack or systemic embolism) (figure 2). Conclusion AF patients at intermediate risk of stroke rapidly develop an increased stroke risk. In this nationwide study, more than half of AF patients at intermediate risk of stroke acquired a new risk factor during a median follow-up time of 16 months. The average annual risk of an increase in the CHA2DS2-VASc score was 29%. Intermediate-risk AF patients should be regularly reassessed, especially to avoid undertreatment if anticoagulation has previously been withheld.

Net clinical benefit of oral anticoagulants in Korean atrial fibrillation patients with low to intermediate stroke risk: A report from the Clinical Survey on Stroke Prevention in patients with Atrial Fibrillation (CS-SPAF).

The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non-gender CHA2DS2-VASc scores 0-1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non-gender CHA2DS2-VASc scores 0-1. This multi-center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-VKA oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0-1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed-up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37-4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56-5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score=0). In the Korean AF cohort at non-gender CHA2DS2-VASc scores 0-1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1.

Abstract 13987: Cost-Effectiveness of Direct Oral Anticoagulant vs Warfarin Among Atrial Fibrillation Patients With Intermediate Stroke Risk

Background: Several studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data. Methods: We identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained. Results: The total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was $2,874, $5,761, $5,151, $5,761 and $5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99, $8,426.71, -$8,483.04 and $18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis. Conclusion: Our findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk. Figure 1. Cost-effectiveness acceptability curve of Warfarin vs. DOACs in AF patients with intermediate stroke risk.

Stroke rates in non-anticoagulated individuals with and without atrial fibrillation and one non-sex CHA2DS2-VASc risk factor: a nationwide registry-based cohort (Atrial Fibrillation in Norway – AFNOR)

Abstract Background Stroke prevention is fundamental in the management of atrial fibrillation (AF). However, in patients with intermediate risk of stroke (CHA2DS2-VASc score 2 in women; 1 in men) the net clinical benefit of oral anticoagulant (OAC) treatment is uncertain, as the treatment effect must be carefully balanced against the potential bleeding risk. Moreover, multiple risk factors included in the CHA2DS2-VASc score increase the risk of stroke independent of AF. Purpose We aimed to compare rates of ischemic and haemorrhagic stroke between non-anticoagulated individuals with and without AF in a nationwide cohort of individuals at intermediate risk of stroke. Method We identified a cohort of non-anticoagulated Norwegian individuals with and without non-valvular AF aged ≥18 years, with one non-sex CHA2DS2-VASc risk factor linking data from the Norwegian Population Registry, Patient Registry, Prescription Database and Cause of Death Registry. AF and comorbidities were identified with minimum three-year look-back period at study start and successively during follow up. Individuals without AF entered the study at date of first registered non-sex CHA2DS2-VASc risk factor while individuals with AF entered at the first date when both AF and first CHA2DS2-VASc risk factor were registered. Individuals with and without AF were followed from study start in 2011 until occurrence of stroke, death, emigration, OAC claim, increased CHA2DS2-VASc score or end of follow-up on December 31, 2018. Rates of ischemic and haemorrhagic stroke were calculated as the number of stroke cases per 100 person-years with 95% confidence intervals (CI). Results During 2011–2018, a total of 61,762 individuals with AF at intermediate risk of stroke and no previous OAC use were identified (mean age 63.2±7.6 years (SD); 37% women). In the AF population, a total of 1,304 ischemic strokes were registered during 109,881 person-years, and 127 haemorrhagic strokes during 109,559 person-years. In the corresponding intermediate risk non-AF population, 1,099,655 individuals (mean age 59.5±10.2 years (SD); 49.5% women) were identified, with a total of 6,081 ischemic strokes during 4,037,940 person-years and 3,037 haemorrhagic strokes during 4,022,952 person-years. The rate of ischemic stroke was 1.19 (95% CI, 1.12–1.25) in AF-patients and 0.15 (95% CI, 0.15–0.15) in non-AF individuals per 100 person-years, corresponding to a rate difference of 1.04 excess stroke cases per 100 person-years in AF patients. The haemorrhagic stroke rate was 0.12 (95% CI, 0.10–0.14) in AF-patients and 0.08 (95% CI, 0.07–0.08) per 100 person-years in non-AF individuals. Similar rate differences were seen in both men and women. Conclusion In a nationwide population with one non-sex CHA2DS2-VASc risk factor and without OAC treatment, we found higher stroke rate in AF patients compared to the rest of the population without AF, with a stroke rate difference of ∼1% per year. Haemorrhagic stroke rates were generally low. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): South-Eastern Norway Regional Health Authority

Net clinical benefit of NOAC in Korean atrial fibrillation patients with low to intermediate stroke risk

Abstract Background The balance of stroke risk reduction and potential hemorrhagic risk associated with anti-thrombotic treatment (ATT) remain unclear in Korean atrial fibrillation (AF) patients with low to intermediate stroke risk, defined as non-gender CHA2DS2-VASc score 0–1. Purpose The net clinical benefit (NCB) analysis of ATT may be helpful to guide stroke prevention strategy in AF patients with non-gender CHA2DS2-VASc score 0–1. Methods This Korean multi-center cohort study retrospectively evaluated the clinical outcomes with single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-vitamin K antagonist oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0–1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/ml], Creatinine clearance [&amp;lt;50 ml/min/1.73 m2], and Dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT including thromboembolic and major bleeding events. Results We included 2465 patients (56.2±9.5 years; female, 665 [27.0%]) followed-up for 4.0±2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. In comparison with no treatment, only NOAC demonstrated a positive tendency for stroke prevention (NOAC, NCB 0.47, 95% confidence interval [CI] −0.40 to 2.10; SAPT, NCB −0.31, 95% CI −1.48 to 1.40; and VKA, NCB −1.26, 95% CI −2.97 to 0.67). With detailed risk stratification with ABCD score, NOAC showed a significant NCB for stroke prevention compared with SAPT and VKA (SAPT vs. NOAC, NCB 1.6, 95% CI 0.26–3.50; VKA vs. NOAC, NCB 1.96, 95% CI 0.47–4.16) in patients with ABCD score ≥1. ATT failed to show NCB in patients with truly low stroke risk defined as ABCD score=0. Conclusion Korean AF cohort with low to intermediate stroke risk indicates that, in comparison with no ATT, only ATT with NOAC showed marginal NCB. With further risk stratification by ABCD score, NOAC showed significant advantages over other ATTs (VKA or SAPT) in patients with ABCD ≥1. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Korean Disease Control and Prevention Agency

The 2nd European Carotid Surgery Trial (ECST-2): rationale and protocol for a randomised clinical trial comparing immediate revascularisation versus optimised medical therapy alone in patients with symptomatic and asymptomatic carotid stenosis at low to intermediate risk of stroke

BackgroundCarotid endarterectomy is currently recommended for patients with recently symptomatic carotid stenosis ≥50%, based on randomised trials conducted 30 years ago. Several factors such as carotid plaque ulceration, age and associated comorbidities might influence the risk-benefit ratio of carotid revascularisation. A model developed in previous trials that calculates the future risk of stroke based on these features can be used to stratify patients into low, intermediate or high risk. Since the original trials, medical treatment has improved significantly. Our hypothesis is that patients with carotid stenosis ≥50% associated with a low to intermediate risk of stroke will not benefit from additional carotid revascularisation when treated with optimised medical therapy. We also hypothesise that prediction of future risk of stroke in individual patients with carotid stenosis can be improved using the results of magnetic resonance imaging (MRI) of the carotid plaque.MethodsPatients are randomised between immediate revascularisation plus OMT versus OMT alone. Suitable patients are those with asymptomatic or symptomatic carotid stenosis ≥50% with an estimated 5-year risk of stroke of <20%, as calculated using the Carotid Artery Risk score. MRI of the brain at baseline and during follow-up will be used as a blinded measure to assess the incidence of silent infarction and haemorrhage, while carotid plaque MRI at baseline will be used to investigate the hypotheses that plaque characteristics determine future stroke risk and help identify a subgroup of patients that will benefit from revascularisation. An initial analysis will be conducted after recruitment of 320 patients with baseline MRI and a minimum of 2 years of follow-up, to provide data to inform the design and sample size for a continuation or re-launch of the study. The primary outcome measure of this initial analysis is the combined 2-year rate of any clinically manifest stroke, new cerebral infarct on MRI, myocardial infarction or periprocedural death.DiscussionECST-2 will provide new data on the efficacy of modern optimal medical therapy alone versus added carotid revascularisation in patients with carotid stenosis at low to intermediate risk of future stroke selected by individualised risk assessment. We anticipate that the results of baseline brain and carotid plaque MRI will provide data to improve the prediction of the risk of stroke and the effect of treatment in patients with carotid stenosis.Trial registrationISRCTN registry ISRCTN97744893. Registered on 05 July 2012

Thromboembolic Risk in Patients With Pneumonia and New-Onset Atrial Fibrillation Not Receiving Anticoagulation Therapy

New-onset atrial fibrillation (AF) is commonly reported in patients with severe infections. However, the absolute risk of thromboembolic events without anticoagulation remains unknown. To investigate the thromboembolic risks associated with AF in patients with pneumonia, assess the risk of recurrent AF, and examine the association of initiation of anticoagulation therapy with new-onset AF. This population-based cohort study used linked Danish nationwide registries. Participants included patients hospitalized with incident community-acquired pneumonia in Denmark from 1998 to 2018. Statistical analysis was performed from August 15, 2021, to March 12, 2022. New-onset AF. Thromboembolic events, recurrent AF, and all-cause death. Estimated risks were calculated for thromboembolism without anticoagulation therapy, new hospital or outpatient clinic contact with AF, initiation of anticoagulation therapy, and all-cause death at 1 and 3 years of follow-up. Death was treated as a competing risk, and inverse probability of censoring weights was used to account for patient censoring if they initiated anticoagulation therapy conditioned on AF. Among 274 196 patients hospitalized for community-acquired pneumonia, 6553 patients (mean age [SD], 79.1 [11.0] years; 3405 women [52.0%]) developed new-onset AF. The 1-year risk of thromboembolism was 0.8% (95% CI, 0.8%-0.8%) in patients without AF vs 2.1% (95% CI, 1.8%-2.5%) in patients with new-onset AF without anticoagulation; this risk was 1.4% (95% CI, 1.0%-2.0%) among patients with AF with intermediate stroke risk and 2.8% (95% CI, 2.3%-3.4%) in patients with AF with high stroke risk. Three-year risks were 3.5% (95% CI, 2.8%-4.3%) among patients with intermediate stroke risk and 5.3% (95% CI, 4.4%-6.5%) among patients with high stroke risk. Among patients with new-onset AF, 32.9% (95% CI, 31.8%-34.1%) had a new hospital contact with AF, and 14.0% (95% CI, 13.2%-14.9%) initiated anticoagulation therapy during the 3 years after incident AF diagnosis. At 3 years, the all-cause mortality rate was 25.7% (95% CI, 25.6%-25.9%) in patients with pneumonia without AF vs 49.8% (95% CI, 48.6%-51.1%) in patients with new-onset AF. This cohort study found that new-onset AF after community-acquired pneumonia was associated with an increased risk of thromboembolism, which may warrant anticoagulation therapy. Approximately one-third of patients had a new hospital or outpatient clinic contact for AF during the 3-year follow-up, suggesting that AF triggered by acute infections is not a transient, self-terminating condition that reverses with resolution of the infection.

Frequency of cardioversions as an additional risk factor for stroke in atrial fibrillation – the FinCV-4 study

Background Patients with atrial fibrillation (AF) are selected for oral anticoagulation based on individual patient characteristics. There is little information on how clinical AF burden associates with the risk of ischaemic stroke or systemic embolism (SSE). The aim of this study was to explore the association of the frequency of cardioversions (CV) as a measure of clinical AF burden on the long-term SSE risk, with a focus on patients at intermediate stroke risk based on CHA2DS2-VASc score. For these patients, additional SSE risk stratification by assessing CV frequency may aid in the decision on whether to initiate oral anticoagulation. Methods This retrospective analysis of FinCV Study from years 2003–2010 included 2074 patients who were not using any oral anticoagulation (long term or temporary) after CVs and undergoing a total of 6534 CVs for AF from emergency departments of three hospitals. Two study groups were formed: high CV frequency (mean interval between CVs ≤12 months and low frequency (>12 months). Results A total of 107 SSEs occurred during a mean follow-up of 5.4 years. The event rates per 100 patient-years were 1.82 and 0.67 in high versus low CV frequency groups, respectively. After adjustment for CHA2DS2-VASc score, CV frequency independently predicted SSE (HR, 2.87 [95% CI, 1.47 to 5.64]; p = .002) at 3 years. Competing risk analysis also identified CV frequency (sHR, 2.70 [95% CI, 1.38–5.31]; p = .004) as an independent predictor for SSE. In patients with CHA2DS2-VASc score 1 and low CV frequency, the SSE risk was only 0.08 per 100 patient-years. Conclusions Frequency of CVs for symptomatic AF episodes provides additional information on stroke risk in AF patients with CHA2DS2-VASc score 1. Key messages This retrospective study offers a unique opportunity to observe the natural course of AF patients with infrequent episodes of clinical arrhythmia when they were not using OAC (before introduction of CHA2DS2-VASc score). Stroke or systemic embolism rate was very low (0.08 per 100 patient-years) in patients with one CHA2DS2-VASc point who visited the emergency room for cardioversion less than once a year. Frequency of cardioversions can be used for additional risk stratification in patients at intermediate risk of stroke based on CHA2DS2-VASc score.

Cost-effectiveness of Direct Oral Anticoagulant vs. Warfarin Among Atrial Fibrillation Patients With Intermediate Stroke Risk.

BackgroundSeveral studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data.MethodsWe identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained.ResultsThe total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was $2,874, $5,761, $5,151, $5,761 and $5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99, $8,426.71, -$8,483.04 and $18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis.ConclusionOur findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk.

Oral anticoagulation in atrial fibrillation patients at intermediate risk of stroke: a nationwide registry-based cohort (Atrial Fibrillation in Norway – AFNOR)

Abstract Background The effect of oral anticoagulants (OAC) on prevention of stroke must be carefully balanced against the potential risk of bleeding in patients with atrial fibrillation (AF). The net benefit of OAC in AF patients at intermediate risk of stroke remains unclear. Aim We aimed to determine whether the rates of ischemic and haemorrhagic stroke differ between users and non-users of OAC in a nationwide cohort of AF patients at intermediate risk of stroke. Method We investigated the association between initiation of OAC treatment and rates of ischemic and haemorrhagic stroke in a cohort of Norwegian patients with non-valvular AF aged ≥18 years with one non-sex CHA2DS2-VASc risk factor registered from 2011 to 2018, linking data from the Norwegian Population Registry, Patient Registry, Prescription Database and Cause of Death Registry. Individuals using OAC at baseline were excluded. Each individual had at least a three years look-back period for identification of their first non-sex CHA2DS2-VASc risk factor, after which they entered the study cohort and were followed until occurrence of stroke, death, emigration, higher CHA2DS2-VASc score or end of follow-up on December 31, 2018. Individuals were defined as exposed to OAC from the first redeemed prescription of OAC with a reimbursement code for AF and throughout follow-up. Rates of ischemic and haemorrhagic stroke were calculated as the number of stroke cases per 100 person-years, with 95% confidence intervals (CI). Results During 2011–2018, a total of 61,631 individuals with AF and intermediate risk of stroke were included (mean age 63,8±7,6 years (SD); 37% women), of whom 75% initiated OAC treatment. In total, 1709 ischemic strokes (405 cases in OAC users and 1304 in non-users) were registered during 214,738 person-years, and 378 haemorrhagic strokes (251 cases in OAC users and 127 in non-users) during 213,487 person-years. The rate of ischemic stroke was 0.39 (95% CI, 0.35–0.43) and 1.19 (95% CI, 1.12–1.25) per 100 person-years in OAC users and non-users, respectively. The haemorrhagic stroke rate was 0.24 (95% CI, 0.21–0-27) and 0.12 (95% CI, 0.10–0.14) per 100 person-years in OAC users and non-users, respectively. Both ischemic and haemorrhagic stroke rates were highest among those over 65 years of age (Figure 1). Conclusion In a nationwide cohort of Norwegian AF patients at intermediate risk of stroke, three out of four initiated treatment with OAC. Use of OAC was associated with a considerably lower rate of ischemic stroke compared to non-OAC use. Although haemorrhagic stroke rates were increased in the OAC-users vs. non-users, the hemorrhagic stroke rates were generally low. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Vestre Viken Health Trust Figure 1. Rates of ischemic and haemorrhagic stroke per 100 person-years in AF-patients at intermediate risk of stroke (CHA2DS2-VASc score 1 in men, score 2 in women) by OAC use during 2011 to 2018. Age corresponds to age at attainment of the first non-sex CHA2DS2-VASc risk factor.

Adherence to the 4S-AF Scheme in the Balkan region: insights from the BALKAN-AF survey

Abstract Background Current European Society of Cardiology guidelines on atrial fibrillation (AF) propose a structured characterization of AF in order to facilitate the evaluation of patients by physicians at all healthcare levels. The 4S-AF structured scheme includes four domains: stroke risk, symptoms, severity of AF burden and substrate severity. Purpose To evaluate the adherence to the 4S-AF scheme in patients with high risk of stroke (CHA2DS2-VASc score ≥3 in females or ≥2 in males) in the post-hoc analysis of the BALKAN-AF dataset. Methods Prospective enrolment of consecutive patients with electrocardiographically documented AF was conducted in seven Balkan countries. Results Of the 2,712 enrolled patients, 2,712 (100.0%) had data on CHA2DS2-VASc score. 162 (6.0%) had truly low risk of stroke (CHA2DS2-VASc score of 0 in males and 1 in females). 2099 (77.4%) of patients had high risk of stroke and 613 (22.6%) individuals had low or intermediate risk of stroke (CHA2DS2-VASc score &amp;lt;3 in females or &amp;lt;2 in males). 75 (46.3%) of patients with truly low stroke risk and 1555 (74.1%) of patients with high risk of stroke were offered oral anticoagulants (OAC). Of the 2,712 patients, 2,677 (98.7%) had data on European Heart Rhythm Association (EHRA) symptom score. Among 2,099 patients with high risk of stroke, 703 (33.4%) individuals had EHRA symptom score of 3 or 4. 207 (29.4%) of patients with EHRA symptom score of 3 or 4 and high risk of stroke were offered rhythm control strategy. 620 (55.2%) of patients with first diagnosed AF or paroxysmal AF with high risk of stroke were offered rhythm control strategy. 1927 (91.8%) of patients with high risk of stroke had ≥2 comorbidities. Mean left atrial diameter in patients with high risk of stroke was 46.5±7.8 mm. Conclusions OAC overuse was seen in patients with truly low stroke risk, whist OAC underuse was evident in patients with high risk of stroke. The proportion of highly symptomatic patients (EHRA 3 or 4) with high risk of stroke who were offered rhythm control strategy was low. The proportion of patients with first diagnosed AF or paroxysmal AF with high risk of stroke who received rhythm control was small. The majority of AF patients with high risk of stroke had ≥2 comorbidities. Overall, treatment decision-making was not based on the 4S-AF scheme. Funding Acknowledgement Type of funding sources: None.

Should oral anticoagulants still be prescribed to patients with atrial fibrillation with a single stroke risk factor but at high bleeding risk? A nationwide cohort study.

To investigate the co-distributions of stroke and bleeding risks in Asian patients with atrial fibrillation (AF) and the clinical benefits of oral anticoagulants (OACs) among AF patients with a single stroke risk factor but at high bleeding risk. From 1 January 2001 to 31 December 2016, a total of 404949 AF patients were retrospectively identified from Taiwan National Health Insurance Research Database. Stroke risk was assessed using the CHA2DS2-VASc score and was categorized into low risk (score=0 for males and 1 for females), intermediate risk (i.e. a single non-sex stroke risk factor; score=1 for males and 2 for females), and high risk (score ≥2 for males and ≥3 for females). A high risk of bleeding was defined as a HAS-BLED score ≥3. Around 57.5% of AF patients were at high risk for both stroke and bleeding, and most patients (97.6%) with a low stroke risk were also at low risk for bleeding. Around 18.3% of patients with a CHA2DS2-VASc score of 1 (males) or 2 (females) were at high bleeding risk, and the use of OACs in such patients was associated with a lower risk of composite adverse events of ischaemic stroke, intracranial haemorrhage, or mortality (4.19/100 person-years vs. 5.22/100 person-years, adjusted hazard ratio=0.781, P=0.04). For AF patients with an intermediate risk of stroke (i.e. a single non-sex stroke risk factor) but at high bleeding risk, the use of OACs was still significantly associated with a better overall clinical outcome.

Does the CHA2DS2-VASc scale sufficiently predict the risk of left atrial appendage thrombus in patients with diagnosed atrial fibrillation treated with non-vitamin K oral anticoagulants?

The CHA2DS2-VASc scale does not include potential risk factors for left atrial appendage thrombus (LAAT) formation such as a form of atrial fibrillation (AF) and impaired kidney function. The real risk of thromboembolic complications in AF patients is still unclear as well as an optimal anticoagulant treatment in males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2.The aim of this study was to compare the predictive value of the CHA2DS2-VASc scale and other scales to estimate the risk of LAAT formation in AF patients treated with non-vitamin K oral anticoagulants (NOACs) and to assess the prevalence of thrombi in patients at intermediate risk of stroke.The observational study included consecutive patients with a diagnosis of non-valvular AF treated with NOACs, admitted to 3 high-reference institutions between 2013 and 2018. All individuals underwent transoesophageal echocardiography before cardioversion or ablation.Out of 1163 enrolled AF patients (62.1% male, mean age 62 years) the LAAT had been detected in 50 individuals (4.3%). Among patients with LAAT, 1 patient (2.0%) was classified as a low-risk category, 9 (18.0%) were at intermediate-risk, and 40 (80.0%) were at high risk of thromboembolic complications according to CHA2DS2-VASc scale. All patients were treated with NOACs: 51.0% rivaroxaban, 47.1% dabigatran, and 1.9% apixaban.Patients at intermediate stroke-risk with detected LAAT had higher R2CHADS2 score (2.1 ± 1.2 vs 1.2 ± 0.8, P = .007), higher CHA2DS2-VASc-RAF score (6.4 ± 4.4 vs 3.7 ± 2.6, P = .027) and more often had an estimated glomerular filtration rate below 56 mL/min/1.73 m2 (44.4% vs 13.2%, P = .026) compared to patients without LAAT. The receiver operating characteristics revealed that the CHA2DS2-VASc-RAF scale had better predictive ability to distinguish between patients with and without LAAT in the study group than CHA2DS2-VASc (P = .0006), CHADS2 (P = .0006) and R2CHADS2 scale (P = .0140).The CHA2DS2-VASc scale should be supplemented with an assessment of renal function and form of AF to improve stroke risk estimation. The application of additional scales to estimate the risk of LAAT might be especially useful among males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2.

Age Threshold for Ischemic Stroke Risk in Atrial Fibrillation.

Background and Purpose- Although older age is one of the most important risk factor for stroke in atrial fibrillation (AF), the appropriate age threshold (eg, CHA2DS2-VASc score [congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65-74 years, female], 1 point for age 65-74 years, 2 points for age ≥75 years) for increased risk is controversial because actual age thresholds may differ between countries and ethnic groups. We investigated the age threshold for ischemic stroke risk among Asian AF patients. Methods- Using National Health Insurance Service database, including 426 650 oral anticoagulant-naive nonvalvular AF patients from 2005 to 2015, with ≤2 nongender-related CHA2DS2-VASc risk scores (CHA2DS2-VASc score 0-2 in males, 1-3 in females), we assessed the risk of ischemic stroke in AF patients according to the age. Results- Patients who fulfill the age risk criterion (age, 65-74 years) without other risk factors showed a significantly higher risk of stroke (4.76 per 100 person-years [100PY]; adjusted hazard ratio, 2.25; 95% confidence interval [CI], 2.17-2.36) compared with patients with 1 risk score other than age (1.87/100PY). Patients aged 55 to 59 years with no risk factors showed similar risk of stroke (1.94/100PY; adjusted hazard ratio, 0.95; 95% confidence interval, 0.90-1.00) than patients with 1 risk score (2.06/100PY). Patients aged 65 to 69 years and no other risk factors had similar stroke risk (4.08/100PY; adjusted hazard ratio, 0.93; 95% confidence interval, 0.90-0.97) than patients with 2 nongender-related risk scores (4.42/100PY). Conclusions- Older age is the most important predictor of ischemic stroke in AF, particularly for patients with low to intermediate risk of stroke. These nationwide data suggest lowering the current age threshold (age, ≥65 years) in the CHA2DS2-VASc score to age ≥55 years might be appropriate among Asian patients with AF.

Oral anticoagulation therapy upon discharge in hospitalized patients with nonvalvular atrial fibrillation: a retrospective cohort study

ABSTRACTObjectives: Availability of direct oral anticoagulants and CHA2DS2VASc/HAS-BLED scoring tools underscore the importance of appropriate and safe use of oral anticoagulation therapy (OACT). The purpose of this study was to evaluate stroke prevention pharmacotherapy in adult patients with nonvalvular atrial fibrillation (NVAF) discharged from a large, community-based hospital.Methods: A retrospective cohort study was conducted using a de-identified data collection sheet for data extraction (demographics, admitting diagnosis, OACT prior to admission and at discharge, concomitant medications that could increase bleed risk and/or acid-suppressive therapies). CHA2DS2VASc and HAS-BLED scores were calculated. Descriptive statistics were generated to describe all parameters. Frequency counts and percentages summarized categorical variables while mean ± standard deviation were determined for continuous variables.Results: Data from 180 patients were evaluated and of these 177 (98.3%) received OACT regardless of stroke risk upon discharge, as determined by CHA2DS2VASc scoring tool. The mean CHA2DS2VASc and HAS-BLED scores were 3.61 ± 1.7 and 2.13 ± 1.26, respectively. At discharge, eight patients at low-stroke risk received OACT for unclear reasons, one intermediate-stroke risk patient received aspirin only, and two patients at high-stroke risk did not receive OACT due to concerns about bleeds. In 66 patients at high-bleed risk, only half received concomitant acid-suppressive therapy.Conclusions: Decision to add OACT is often guideline-driven, however, individualized circumstances in which clinicians and patients find themselves are also important considerations. Determination of ischemic stroke risk should be performed with CHA2DS2VASc scoring tool to exclude patients who may not benefit from OACT. HAS-BLED scoring tool should be used to identify any modifiable bleeding risk factors present with subsequent initiation of management strategies. Availability of complete medical histories and meticulous documentation are necessary for multiple clinicians to continuously determine optimal pharmacotherapy during follow-up visits.

Stroke risks and patterns of warfarin therapy among atrial fibrillation patients post radiofrequency ablation: A real-world experience.

We assessed the thromboembolic risks of atrial fibrillation (AF) patients who had undergone radiofrequency ablation (RFA) using the CHADS2-VASc risk scoring system and further investigated the patterns of warfarin use for thromboprophylaxis according to patient thromboembolic risk scores.In this study, we analyzed the stroke risks of patients who had undergone RFA for AF at our hospital between March 2014 and June 2016 using the CHADS2, CHADS2-VASc, and Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (> 65 years) (HAS-BLED) scoring systems. We retrieved medications, co-morbidities, and initial warfarin dosage data. The primary outcome was the percentage of patients initiated with warfarin therapy for stroke prophylaxis in AF who had a CHADS2-VASc score of 0.Totally, 309 patients were initiated with warfarin therapy for stroke prophylaxis in AF post-RFA. The baseline warfarin dosage was 2.76 ± 0.61 mg. The baseline CHADS2-VASC score was 2.93 ± 1.96 and 40 (12.95%) had a CHADS2-VASC score of 0, 42 (13.6%) had a CHADS2-VASCscore of 1, and 227 (73.5%) had a CHADS2-VASC score ≥2. The baseline CHADS2 score was 2.17 ± 1.55 and 48 (15.5%) had a CHADS2 score of 0, 68 (22.0%) had a CHADS2 score of 1, and 193 (62.5%) had a CHADS2 score ≥2. The baseline HAS-BLED score was 1.25 ± 0.91 and 69 (22.3%) had a HAS-BLED score of 0, 121 (39.2%) had a HAS-BLED score of 1, and 119 (38.5%) had a HAS-BLED score ≥2. Patients aged <65 years or 65 years, male and female patients, patients with or without hypertension, coronary heart disease, or diabetes mellitus, and patients with or without previous stroke/transient ischemic attack differed significantly in stroke risks by CHADS2-VASC, CHADS2, and HAS-BLED scores for stroke risks. Patients with different baseline international normalized ratio differed significantly in CHADS2-VASC scores. Furthermore, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and statins were of statistical significance for stroke risks.The majority of AF patients post-RFAs was of high stroke risk and received warfarin thromboprophylaxis in accordance with national guidelines. Our findings suggest that low and intermediate stroke risk patients should be evaluated for stroke risks and risk factors so that tailored warfarin thromboprophylaxis therapy can be given and inappropriate use of warfarin in AF patients can be avoided.

P3596Dabigatran, rivaroxaban, and apixaban versus vitamin K antagonists for atrial fibrillation patients at low to intermediate stroke risk: a Danish nationwide cohort study

P3596Dabigatran, rivaroxaban, and apixaban versus vitamin K antagonists for atrial fibrillation patients at low to intermediate stroke risk: a Danish nationwide cohort study

Biomarker Assays for Personalised Stroke Risk Assessment in Atrial Fibrillation.

Atrial fibrillation is a well-known independent risk factor for stroke yet there is no international consensus on guidelines regarding the introduction of anticoagulation in patients deemed at intermediate risk (e.g. CHA2DS2-VASc of 1). The evolution of cardiac biomarkers such as highly sensitive troponins and B-type natriuretic peptide as well as data on D-dimers, may offer incremental enhancements for personalized thromboembolism risk assessment. These markers provide prognostic data for risk of cardiovascular morbidities associated with atrial fibrillation and offer additional specificity for assessing stroke and thromboembolic risk. These assays may therefore enhance risk prognosis in atrial fibrillation alongside conventional stroke risk stratification tool patients. We seek to explore the application of personalised risk assessment using the biomarkers to aid the clinician treating the patient with atrial fibrillation deemed to be at intermediate risk of stroke. The stroke risk assessment of a patient with an intermediate risk of stroke (CHA2DS2- VASc score 1) may be improved by using cardiac biomarkers such as highly sensitive troponin, BNP and D-dimers. We explore the application of these biomarkers to provide personalised risk assessment to help a patient with AF decide on whether to commence anticoagulation.

CREST-2: Identifying the Best Method of Stroke Prevention for Carotid Artery Stenosis: National Institute of Neurological Disorders and Stroke Organizational Update.

One of the great achievements of modern medicine is the successful prevention of stroke and other cardiovascular diseases. Although the incidence of stroke has substantially declined over the last 30 years, ≈200 000 preventable stroke deaths still occur annually in the United States. According to a recent study based on the Greater Cincinnati/Northern Kentucky Stroke Study, annually ≈41 000 strokes in the United States are attributed to extracranial internal carotid artery stenosis. Early revascularization for symptomatic carotid stenosis—that is, in patients with recent ipsilateral stroke or TIA—is well established as effective at preventing ipsilateral stroke. Carotid stenosis in the absence of symptoms is extremely common, but the best treatment is unclear. While 2 randomized trials showed a benefit of carotid endarterectomy (CEA) over antiplatelet therapy with aspirin, the number needed to treat approaches 200. Does aggressive risk factor control change that balance? Population screening for carotid stenosis followed by revascularization is considered to cause net harm. Are complication rates from endarterectomy and stenting now low enough to justify expanding their indications in asymptomatic patients? The National Institute of Neurological Disorders and Stroke (NINDS)–funded CREST-2 trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) is an ambitious attempt to further refine the treatment of asymptomatic carotid stenosis. As one of the largest randomized stroke prevention trials, the first CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) was designed to compare the safety and efficacy of 2 stroke prevention procedures for carotid artery narrowing—CEA and carotid artery stenting (CAS)—in symptomatic and asymptomatic individuals. Starting in December 2000, this NINDS-funded trial enrolled >2500 patients at 117 sites in the United States and Canada. Because of slow enrollment, the trial took 9 years to complete. In 2010, the results of CREST indicated that the 2 revascularization procedures were equivalent for …