Stroke : Highlights of Selected Articles

Objective: We investigated recurrent stroke volume with nonvalvular atrial fibrillation (NVAF) patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) about clinical backgrounds and number of recurrent stroke. Methods: We administered three NOACs, dabigatran, rivaroxaban and apixaban in 84 post cardioembolic stroke with NVAF. In retrospective study, we measured recurrent stroke volume with MRI volumetry soft and compared them between 7 vitamin K anticoagulant (VKA: warfarin) cases and 10 NOACs cases under anticoagulant therapy. Results: Of 84 cases, 27 cases were started with VKA and switched to NOACs after 7 recurrent stroke. Other 57 cases were directly started with NOACs and 10 cases with NOACs as first anticoagulants had recurrent stroke. The frequency of recurrent stroke during anticoagulant therapy are not different among VKA group and three NOACs group. Recurrent stroke volume is significantly larger in VKA group (27.4 cm3) than in NOACs group (3.3cm3). Conclusions: Secondary prevention with NOACs after stroke might be more beneficial by reducing recurrent infarct volume than VKA.

Background and Objectives: While non-vitamin K antagonist oral anticoagulants (NOACs) show better renal preservation than warfarin in nonvalvular atrial fibrillation (NVAF) patients, real-world evidence within Asian populations remains limited. This study compared the renal outcomes between NOACs and warfarin in Thai patients with NVAF. Materials and Methods: A retrospective cohort study was conducted among NVAF patients who received either NOACs or warfarin from two university hospitals in Thailand from January 2015 to December 2019. The primary outcome was a ≥30% decline in the estimated glomerular filtration rate (eGFR) with a doubling of the serum creatinine (SCr), while acute kidney injury (AKI) and incidence rate of stroke and systemic embolism event (SEE) were secondary outcomes. All outcomes of each NOAC versus the warfarin group were analyzed using Cox proportional hazards regression. Results: A total of 1456 patients were enrolled. During a follow-up period of 24 months, NOACs were associated with a lower risk of a ≥30% decline in the eGFR than warfarin after inverse probability of treatment weighting (IPTW) and multivariable adjustment (adjusted hazard ratio (aHR) of 0.67, 95% confidence interval [CI] 0.45-1.00, p = 0.050). No significant differences were observed between NOACs and warfarin regarding the doubling of SCr (aHR 0.64, 95% CI 0.24-1.72, p = 0.373) or AKI (aHR 0.69, 95% CI 0.41-1.17, p = 0.169), although a trend toward a lower risk was noted in the NOAC group. Similarly, a trend toward a lower risk of the incidence rate of ischemic stroke and SEE were observed in the NOAC group (aHR 0.49, 95% CI 0.22-1.10, p = 0.084). Conclusions: In real-world data, NOACs may be associated with a lower eGFR decline and lower doubling of SCr and AKI than warfarin. Additionally, NOACs may reduce the risk of ischemic stroke and SEE, supporting their potential benefit over warfarin in both renal and thromboembolic outcomes.

Analysis of Recurrent Stroke Volume and Prognosis between Warfarin and Four Non–Vitamin K Antagonist Oral Anticoagulants' Administration for Secondary Prevention of Stroke

Background and Purpose- Warfarin is associated with a better net clinical benefit compared with no treatment in patients with nonvalvular atrial fibrillation (AF) and history of intracranial hemorrhage (ICH). There are limited data on nonvitamin K antagonist oral anticoagulants (NOACs) in these patients, especially in the Asian population. We aimed to compare the effectiveness and safety of NOACs to warfarin in a large-scale nationwide Asian population with AF and a history of ICH. Methods- Using the Korean Health Insurance Review and Assessment database from January 2010 to April 2018, we identified patients with oral anticoagulant naïve nonvalvular AF with a prior spontaneous ICH. For the comparisons, warfarin and NOAC groups were balanced using propensity score weighting. Ischemic stroke, ICH, composite outcome (ischemic stroke+ICH), fatal ischemic stroke, fatal ICH, death from composite outcome, and all-cause death were evaluated as clinical outcomes. Results- Among 5712 patients with AF with prior ICH, 2434 were treated with warfarin and 3278 were treated with NOAC. Baseline characteristics were well-balanced after propensity score weighting (mean age 72.5 years and CHA2DS2-VASc score 4.0). Compared with warfarin, NOAC was associated with lower risks of ischemic stroke (hazard ratio [HR], 0.77 [95% CI, 0.61-0.97]), ICH (HR, 0.66 [95% CI, 0.47-0.92]), and composite outcome (HR, 0.73 [95% CI, 0.60-0.88]). NOAC was associated with lower risks of fatal stroke (HR, 0.54 [95% CI, 0.32-0.89]), death from composite outcome (HR, 0.53 [95% CI, 0.34-0.81]), and all-cause death (HR, 0.83 [95% CI, 0.69-0.99]) than warfarin. NOAC showed nonsignificant trends toward to reduce fatal ICH compared with warfarin (HR, 0.47 [95% CI, 0.20-1.03]). Conclusions- NOAC was associated with a significant lower risk of ICH and ischemic stroke compared with warfarin. NOAC might be a more effective and safer treatment option for Asian patients with nonvalvular AF and a prior history of ICH.

Background Atrial fibrillation (AF) is a risk factor for dementia and oral anticoagulant (OAC) use is associated with a decreased risk of dementia in patients with AF. Objective We sought to find whether the risk of dementia would be different between patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) and those treated with warfarin. Methods Using the Korean National Health Insurance database from January 2014 to December 2017, we identified OAC naïve non-valvular AF patients aged 40 years or older. For the comparison, warfarin and NOAC groups were balanced using the inverse probability of treatment weighting method (IPTW). The primary outcome was incident dementia. Patients were censored at the occurrence of dementia, discontinuation of index treatment, or the end of the study period (December 31, 2018). Results Among 72,846 of total study patients, 25,948 were treated with warfarin and 46,898 were treated with NOAC (17,193 with rivaroxaban, 9,882 with dabigatran, 11,992 with apixaban, and 7,831 with edoxaban). Crude incidence of dementia was 4.65 per 100 person-years in warfarin group and 4.98 per 100 person years in NOAC group. Baseline characteristics were well-balanced after IPTW (mean age 72 years, 93% CHA2DS2-VASc ≥2, 58% men). Compared to warfarin, NOAC showed a comparable risk of dementia (hazard ratio [HR] 0.944, 95% confidence interval [CI] 0.934–1.059), vascular dementia (HR 0.921, 95% CI 0.814–1.043) and Alzheimer dementia (HR 1.101, 95% CI 1.019–1.191). When comparing individual NOACs with warfarin, edoxaban was associated with a lower risk of dementia (HR 0.830, 95% CI 0.740–0.931). Rivaroxaban (HR 0.767, 95% CI 0.648–0.907) and edoxaban (HR 0.786, 95% CI 0.620–0.996) were associated with a lower risk of vascular dementia than warfarin. In subgroup analyses, NOAC was associated with a lower incidence of dementia than warfarin particularly in patients with prior stroke (HR 0.891, 95% CI 0.820–0.968) and in patients aged 65–74 years (HR 0.815, 95% CI 0.709–0.936). Conclusion In this large Asian population with AF, NOAC showed a comparable result with warfarin on the risk of dementia. Edoxaban was associated with a lower risk of dementia. NOAC appeared more beneficial especially in those with AF who had a history of prior stroke and aged 65–74 years. Funding Acknowledgement Type of funding source: None

<p> </p> <p><strong>Objective: </strong>Patients with type 2 diabetes are at higher fracture risk owing to the attenuated bone turnover and impaired bone microarchitecture. The comparative effect of warfarin over non-vitamin K antagonist oral anticoagulants (NOACs) on incident fractures among patients with type 2 diabetes comorbid with atrial fibrillation (AF) remains to be elucidated.</p> <p><strong>Research Design and Methods: </strong>This was a retrospective propensity-score weighted population-based cohort study of adults with type 2 diabetes and AF who were started on warfarin or NOAC between 2005 and 2019, identified from the electronic database of the Hong Kong Hospital Authority. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, proximal humerus and wrist). Hazard ratios (HR) were calculated using Cox proportional hazard regression models.</p> <p><strong>Results: </strong>15,770 type 2 diabetes patients comorbid with AF were included (9,288 on NOAC and 6,482 on warfarin). During a median follow-up of 20 months, 551 patients (3.5%) sustained major osteoporotic fractures (201 in NOAC group [2.2%]; 350 in warfarin group [5.4%]). The adjusted cumulative incidence was lower among NOAC users than warfarin users (HR 0.80, 95% CI 0.64-0.99, p=0.044). Subgroup analyses showed consistent protective effects against major osteoporotic fractures among NOAC users across sex, age, HbA1c, duration of diabetes and history of severe hypoglycemia, compared with warfarin users. </p> <p><strong>Conclusions: </strong>NOAC use was associated with a lower risk of major osteoporotic fractures than warfarin use, among type 2 diabetes patients comorbid with AF. NOAC may be the preferred anticoagulant from the perspective of bone health.</p>

<p> </p> <p><strong>Objective: </strong>Patients with type 2 diabetes are at higher fracture risk owing to the attenuated bone turnover and impaired bone microarchitecture. The comparative effect of warfarin over non-vitamin K antagonist oral anticoagulants (NOACs) on incident fractures among patients with type 2 diabetes comorbid with atrial fibrillation (AF) remains to be elucidated.</p> <p><strong>Research Design and Methods: </strong>This was a retrospective propensity-score weighted population-based cohort study of adults with type 2 diabetes and AF who were started on warfarin or NOAC between 2005 and 2019, identified from the electronic database of the Hong Kong Hospital Authority. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, proximal humerus and wrist). Hazard ratios (HR) were calculated using Cox proportional hazard regression models.</p> <p><strong>Results: </strong>15,770 type 2 diabetes patients comorbid with AF were included (9,288 on NOAC and 6,482 on warfarin). During a median follow-up of 20 months, 551 patients (3.5%) sustained major osteoporotic fractures (201 in NOAC group [2.2%]; 350 in warfarin group [5.4%]). The adjusted cumulative incidence was lower among NOAC users than warfarin users (HR 0.80, 95% CI 0.64-0.99, p=0.044). Subgroup analyses showed consistent protective effects against major osteoporotic fractures among NOAC users across sex, age, HbA1c, duration of diabetes and history of severe hypoglycemia, compared with warfarin users. </p> <p><strong>Conclusions: </strong>NOAC use was associated with a lower risk of major osteoporotic fractures than warfarin use, among type 2 diabetes patients comorbid with AF. NOAC may be the preferred anticoagulant from the perspective of bone health.</p>

Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs) are equivalent to warfarin in preventing thromboembolism in patients with atrial fibrillation (AF). Recently, Total Thrombus-formation Analysis System (T-TAS) was developed as an easy-to-use system for quantitative analysis of thrombus formation using microchips with thrombogenic surfaces (collagen, PL chip; collagen plus tissue factor, AR chip). Hypothesis: We evaluated the efficacy and safety of NOACs using the T-TAS in AF patients undergoing radiofrequency catheter ablation (RFCA). Methods: After exclusion of 19 from 121 consecutive patients undergoing RFCA for AF, the remaining 102 patients were divided into two groups; AF patients treated with warfarin (n=28), and NOACs (n=74). Blood samples obtained on the day (anticoagulant-free point), 3 days and 1 month after RFCA were used in T-TAS to compute the thrombus formation area under the curve (AUC) (PL24-AUC10, AUC for PL chip; AR10-AUC30, for AR chip). Results and Conclusion: The AR10-AUC30 and PL24-AUC10 levels were identical between the warfarin and NOACs groups on the day of RFCA (1708.5±162.1 vs 1757.5±138.0 in AR10-AUC30, p=0.13 and 389.1±95.5 vs 391.7±76.0 in PL24-AUC10, p=0.94, respectively). AR10-AUC30, but not PL24-AUC10 levels, was significantly lower in warfarin and NOACs groups at 3 days and 1 month after RFCA. Multiple logistic regression analysis identified AR10-AUC30 levels on the day of RFCA as a significant predictor of bleeding events in the period of three months after RFCA [odds ratio (OR) 20.6; 95% confidence interval (95%CI): 2.46 to 172.6; p=0.005]. Receiver-operating characteristic analysis showed that AR10-AUC30 levels on the day of RFCA significantly predicted bleeding events [AUC 0.849 (95%CI: 0.719-0.979; p<0.001)]. The cut-off levels of AR10-AUC30 were 1647.6 for identification of bleeding events within three months after RFCA. These results suggested that AR10-AUC30 level determined by T-TAS is a potentially useful marker for assessment of the efficacy and safety of anti-coagulant therapy including warfarin and NOACs, in AF patients undergoing RFCA.

To evaluate the fracture risk among patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. We conducted a real-world nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. All adult patients in Taiwan newly diagnosed with AF between 2012 and 2016 who received NOACs or warfarin were enrolled and followed up until 2017. Patients treated with NOACs were sub-grouped according to the NOAC used (dabigatran, rivaroxaban, and apixaban). Propensity score matching was performed for each head-to-head comparison. Cox regression analysis, with a shared frailty model, was used to calculate the adjusted hazard ratios (aHRs) for hip, vertebral, and humerus/forearm/wrist fractures. After matching, 19414 patients were included (9707 in each NOAC and warfarin groups). The median follow-up time was 2.4 years. Compared with warfarin, NOACs were associated with a reduced fracture risk [aHR = 0.84, 95% confidence interval (CI) = 0.77-0.93; P < 0.001]. Sub-analyses revealed that each NOAC, namely dabigatran (aHR = 0.88, 95% CI = 0.78-0.99; P = 0.027), rivaroxaban (aHR = 0.81, 95% CI = 0.72-0.90; P < 0.001), and apixaban (aHR = 0.67, 95% CI = 0.52-0.87; P = 0.003), had a reduced fracture risk. Analyses including all eligible patients, without propensity score matching, generated similar results. Compared with warfarin, NOAC was associated with a reduced fracture risk among AF patients. Therefore, if oral anticoagulants are indicated, NOACs rather than warfarin should be considered to lower the risk of fractures. However, further studies are needed to investigate the underlying mechanisms and elucidate causality.

Catheter ablation has been established as a rhythm control strategy in selected patients with atrial fibrillation (AF) who have failed or wish to avoid anti-arrhythmic drugs. Uninterrupted oral anticoagulation with vitamin K antagonists (VKAs) peri-ablation is associated with a lower risk of thromboembolic and bleeding complications as compared to interrupted oral anticoagulation and bridging heparin. However, a substantial portion of patients with AF are treated with non-vitamin K antagonist oral anticoagulants (NOACs). Herein, we perform an in-depth review and comparison of three recent randomized trials of uninterrupted oral anticoagulation with NOACs vs VKAs in patients undergoing AF catheter ablation. Furthermore, we report pooled results of these randomized trials. The pooled incidence of major bleeding was significantly lower with NOACs as compared to VKAs (2% vs 4.9%, respectively; odds ratio [OR] 0.40; 95% confidence intervals [CI] 0.16-0.99). Similarly, cardiac tamponade was also reduced in the NOAC group (0.4% vs 1.5%; OR 0.27; 95% CI 0.07-0.97). Thromboembolic complications were not significantly different between groups. Overall, these findings support the 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement's class I recommendation for uninterrupted NOAC use in patients undergoing AF catheter ablation.

Non-vitamin K antagonist oral anticoagulants (NOACs) were introduced to prevent systemic embolism in patients with non-valvular atrial fibrillation (AF), and the use of NOACs for secondary prevention of cardioembolic stroke in patients with AF has gradually increased. Recently, NOACs were also approved for the prevention for deep venous thrombosis. Therefore, ischemic stroke patients with paradoxical emboli who have right-to-left shunt (such as patent foramen ovale or pulmonary arteriovenous fistula) and deep venous thrombosis may be treated with NOACs. In addition, a new clinical concept, termed “Embolic Stroke of Undetermined Source” (ESUS), has recently been suggested. ESUS has been proposed as an indication for anticoagulation, because paroxysmal AF is a potential mechanism of stroke in ESUS patients. Some large randomized clinical trials have been initiated to determine whether NOACs are superior to antiplatelets for the prevention of recurrent stroke in patients with ESUS. In this review, we discuss the potential use of NOACs for secondary stroke prevention among ischemic stroke patients without AF, especially in patients with cryptogenic stroke.

Introduction: Non-vitamin K antagonist oral anticoagulant (NOAC) has been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation since 2014. In previous studies, the stroke risk while taking warfarin was known to be 2 per 100 patient-years and 1.5% per year while taking NOACs. We hypothesized that even if ischemic stroke occurred during anticoagulation therapy with NOACs, the prognosis was likely to be better than that of warfarin. Methods: We obtained data from the nationwide claim database from 2009 to 2019. Patients with atrial fibrillation were identified using the International Classification of Disease Codes. After the diagnosis of atrial fibrillation, patients who developed ischemic stroke during anticoagulation were extracted. The severity of ischemic stroke in the patients was evaluated by the stroke severity index (SSI) calculated by the combination of claim codes. Patients who died within 3-months and within 1-year after ischemic stroke were identified. The patients were divided according to the drug of anticoagulation (warfarin, dabigatran, apixaban, rivaroxaban, edoxaban). Results: A total of 206,848 patients who were newly diagnosed with atrial fibrillation and started anticoagulation therapy were analyzed. Among them, 10,658 patients developed ischemic stroke during follow-up. The anticoagulants administered to these patients were warfarin in 4,423, dabigatran in 965, apixaban in 2,320, rivaroxaban in 1,702, and edoxaban in 1,248. The SSI was highest in the warfarin group (11.43±3.85), and lower in the edoxaban group (8.93±4.03). The order of mortality at 3-months after ischemic stroke was warfarin (17.88%), rivaroxaban (12.34%), dabigatran (9.53%), apixaban (8.28%), and edoxaban group (8.25%). The 1-year mortality rate also showed the same trend. Among NOACs, apixaban had the lowest hazard ratio (HR), HR for 3-months mortality was 0.431 (95% CI 0.367-0.505, p&lt;0.0001), and HR for 1-year mortality was 0.455 (95% CI 0.407-0.510, p&lt;0.0001). Conclusions: In our study, we confirmed that NOAC could lower the risk of death from ischemic stroke than warfarin in patients with atrial fibrillation. Except for rivaroxaban, there was no difference in mortality in the other three NOAC groups.

Objective We aimed to further investigate the efficacy and safety of low-dose NOACs by performing a meta-analysis of cohort studies. Background Meta-analyses of randomized controlled trials (RCTs) have demonstrated that low-dose non-vitamin K antagonist oral anticoagulants (NOACs) showed inferior efficacy compared with standard-dose NOACs, although they are still frequently prescribed for patients with atrial fibrillation (AF) in the clinical practice. Methods Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE were systematically searched from the inception to September 9, 2021, for cohort studies that compared the efficacy and/or safety of low-dose NOACs in patients with AF. The primary outcomes were ischemic stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage (ICH), and gastrointestinal hemorrhage (GH). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the random-effect model. Results Twenty-five publications involving 487856 patients with AF were included. Compared with standard-dose NOACs, low-dose NOACs had comparable risks of ischemic stroke (HR = 1.03, 95% CI 0.96 to 1.11), major bleeding (HR = 1.12, 95% CI 0.97 to 1.28), ICH (HR = 1.09, 95% CI 0.88 to 1.36), and GH (HR = 1.11, 95% CI 0.92 to 1.33), except for a higher risk of mortality (HR = 1.41, 95% CI 1.21 to 1.65). Compared with warfarin, low-dose NOACs were associated with lower risks of ischemic stroke (HR = 0.72, 95% CI .67 to 0.78), mortality (HR = 0.67, 95% CI 0.59 to 0.77), major bleeding (HR = 0.64, 95% CI 0.53 to 0.79), ICH (HR = 0.57, 95% CI 0.42 to 0.77), and GH (HR = 0.78, 95% CI 0.64 to 0.95). Conclusions Low-dose NOACs were comparable to standard-dose NOACs considering risks of ischemic stroke, major bleeding, ICH, and GH, and they were superior to warfarin. Low-dose NOACs might be prescribed effectively and safely for patients with AF. Considering limitations, further well-designed prospective studies are foreseen.

Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study

Effect of Obesity on Patients Admitted for Supraventricular Tachycardia. An Analysis of the Nationwide Inpatient Sample