Higher CHADS2 Research Articles

CHADS2 and CHA2DS2-VASc scores as predictors of platelet reactivity in acute coronary syndrome

BackgroundPlatelet function testing (PFT) in patients treated with P2Y12 inhibitors has been widely evaluated for the prediction of stent thrombosis, myocardial infarction, and bleeding events following percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). Thus, PFT-guided treatment could positively affect patient outcomes. Data regarding clinical parameters for predicting platelet reactivity in ACS patients are limited. Therefore, our study aims to evaluate CHADS2 and CHA2DS2-VASc scores as predictors for platelet reactivity in ACS patients. MethodsTwo hundred and ninety-one consecutive patients who underwent PCI and were treated with aspirin and clopidogrel due to ACS were tested for their CHADS2, CHA2DS2-VASc scores and platelet reactivity using adenosine diphosphate (ADP)-induced aggregation (conventional aggregometry). Patients were classified into groups according to their CHADS2 and CHA2DS2-VASc scores. Low-risk group (0–1 score) for CHADS2 and CHA2DS2-VASc scores and high-risk group (2–6, 2–9) for CHADS2 and CHA2DS2-VASc scores, respectively. Furthermore, platelet reactivity in each group were compared (low CHADS2 group vs high CHADS2 group, and low CHA2DS2-VASc vs high CHA2DS2-VASc). Platelet reactivity was defined as low platelet reactivity (<19 U), optimal platelet reactivity [(OPR); 19–46 U], and high on-treatment platelet reactivity [(HPR); >46 U]. Thereafter receiver operating characteristic curve analysis was conducted to verify whether CHADS2 and CHA2DS2-VASc scores could predict platelet reactivity. ResultsLow CHADS2 and CHA2DS2-VASc scores were significantly correlated with lower mean platelet ADP-induced aggregation as compared with high CHADS2 and CHA2DS2-VASc scores [45.5 U (± 16) vs. 54.8 U (±15) and 44.2 U (±16) vs. 51.0 U (±17), respectively, p = 0.01 for both]. ConclusionIn ACS patients treated with clopidogrel following PCI, high CHADS2 and CHA2DS2-VASc scores correlated with HPR and lower scores correlated with OPR. Further studies are needed to evaluate our findings’ clinical implications.

Dose of Direct Oral Anticoagulants and Adverse Outcomes in Asia

The present study aimed to assess the associations between dosing of DOACs and outcomes in patients with non-valvular atrial fibrillation (NVAF). Direct oral anticoagulants (DOACs) require dose adjustment according to patient or clinical factors for patients with NVAF. We conducted a single-center prospective registry of NVAF patients with DOACs: DIRECT registry (UMIN000033283). In the present analysis, we categorized the patients (n = 2,216) into 5 groups: appropriate standard-dose (n = 907, 40.9%), appropriate low-dose (n = 833, 37.6%), overdose (n = 117, 5.3%), underdose (n = 338, 15.3%), and contraindication (n = 21, 0.9%). The efficacy endpoints were major adverse cardiovascular event (MACE: a composite of all-cause death, myocardial infarction, and stroke/systemic embolism) and its individual components. The safety end points were adverse bleeding events including clinically significant bleeding, major bleeding, and gastro-intestinal bleeding. All NVAF patients treated with DOACs in our institution from 2011 to 2017 were enrolled (71.6 ± 10.8 years, 36.4% female, follow-up duration: 407.2 ± 388.3 days). Appropriate low-dose group were older, more likely female, had a higher CHADS2 and ORBIT scores than the other groups. MACE (7.4%) and clinically significant bleeding (26.2%) occurred most frequently in the appropriate low-dose group. However, after adjustment for various confounders, appropriate dose reduction of DOAC showed 35.4% risk reduction of clinically significant bleeding (adjusted hazard ratio 0.646, 95% CI [0.469 to 0.890], p = 0.007) with no impairment of efficacy end points. In the real-world Asian clinical practice, four fifths of the NVAF patients received appropriate dose of DOACs. Appropriate dose reduction was associated with decrease in clinically significant bleeding and no significant impairment in efficacy end points.

Sex-based differences in procedural complications associated with atrial fibrillation catheter ablation: A systematic review and meta-analysis.

Women undergoing atrial fibrillation catheter ablation (AFCA) have higher rates of vascular complications and major bleeding. However, most studies have been underpowered to detect differences in rarer complications such as stroke/transient ischemic attack (TIA) and procedural mortality. We performed a systematic review of databases (PubMed, World of Science,and Embase) to identify studies published since 2010 reporting AFCA complications by sex. Six complications of interest were(1) vascular/groin complications; (2) pericardial effusion/tamponade; (3) stroke/TIA; (4) permanent phrenic nerve injury; (5) major bleeding; and(6) procedural mortality. For meta-analysis, random effects models were used when heterogeneity between studies was ≥50% (vascular complications andmajor bleeding) and fixed effects models for other endpoints. Of 5716 citations, 19 studies met inclusion criteria, comprising 244,353 patients undergoing AFCA, of whom 33% were women. Women were older (65.3 ± 11.2 vs. 60.4 ± 13.2 years), more likely hypertensive (60.6% vs. 55.5%) and diabetic (18.3% vs. 16.5%), and had higher CHA2 DS2 -VASc scores (3.0 ± 1.8 vs. 1.4 ± 1.4) (p < .0001 for all comparisons). The rates of all six complications were significantly higher in women. However, despite statistically significant differences, the overall incidences of major complications were very low in both sexes: stroke/TIA (women 0.51% vs. men 0.39%) and procedural mortality (women 0.25% vs. men 0.19%). Women experience significantly higher rates of AFCA complications. However, the incidence of major procedural complications is very low in both sexes. The higher rate of complications in women may be partially attributable to older age and a higher prevalence of comorbidities at the time of ablation. More detailed studies are needed to better define the mechanisms of increased risk in women and to identify strategies for closing the sex gap.

Predictors for reduced flow velocity in left atrial appendage during sinus rhythm in patients with atrial fibrillation

Discontinuation of anticoagulation therapy after catheter ablation (CA) for atrial fibrillation (AF) remains controversial. While decreased left atrial appendage flow velocity (LAAFV) during AF leads to left atrial appendage thrombus and embolic events, some AF patients show decreased LAAFV even during sinus rhythm (SR). We studied 392 patients (256 males, 68 ± 10years) who exhibited SR during transesophageal echocardiography (TEE) before CA for AF. Clinical factors, transthoracic echocardiography, and blood samples were obtained before TEE. Reduced LAAFV was defined as < 35cm/s of LAAFV. Reduced LAAFV was observed in 72/392 patients (18%). Reduced LAAFV was significantly associated with high prevalence of non-paroxysmal AF, elevated brain natriuretic peptide (BNP), prior heart failure, high CHADS2 score, high CHA2DS2-VASc score, no beta blocker administration, increased left atrial volume index (LAVI), elevated E/e' ratio, reduced left ventricular ejection fraction and high prevalence of left ventricular hypertrophy. On multivariate analysis, BNP (P = 0.0005, OR 1.045 for each 10pg/ml increase in BNP, 95% CI 1.018-1.073) and LAVI (P = 0.0045, OR 1.044 for each 1 increase in LAVI, 95% CI 1.013-1.077) were associated with decreased LAAFV. The elevated BNP levels and large LAVI predict decreased LAAFV during SR in patients with AF.

Complex Aortic Arch Atherosclerosis in Acute Ischemic Stroke Patients with Non-Valvular Atrial Fibrillation.

Aim: Aortic arch atherosclerosis, particularly complex aortic arch plaques (CAPs), is an important source of cerebral emboli. CAPs and atrial fibrillation (AF) often co-exist; however, the prevalence and risk of CAPs in acute ischemic stroke patients with AF is unclear. Methods: In patients with acute ischemic stroke with non-valvular AF admitted to Jichi Medical University Hospital during April 2016 to September 2019, we retrospectively evaluated the presence of CAPs on transesophageal echocardiography (TEE). Results: CAPs were observed in 41 (38.7 %) of 106 patients with non-valvular AF. Older age, diabetes mellitus, chronic kidney disease, low high-density lipoprotein cholesterol (HDL-C) levels, higher levels of glycohemoglobin A1c (HbA1c), higher CHADS 2 and CHA 2 DS 2 -VASc scores, and intracranial or carotid artery stenosis were more frequently observed in CAPs-positive than in CAPs-negative patients. In multivariable analyses, older age (odds ratio [OR]: 1.2 per year increase; 95% confidence interval [CI]: 1.07–1.24; P ＜0.0001), diabetes mellitus (OR: 4.7; 95%CI: 1.27-17.35; P ＜0.05), and low HDL-C (OR: 0.95 per 1 mg/dl increase; 95%CI: 0.92-0.99; P ＜0.01) were independent risk factors for CAPs. The prevalence of CAPs was age-dependent, and there was a significantly higher risk in patients aged either 75–84 years or ＞84 years than in those aged ＜65 (OR: 7.6; 95%CI: 1.50-38.62, and OR: 32.1; 95%CI: 5.14-200.11, respectively). Conclusions: Even in patients with ischemic stroke with non-valvular AF, concomitant CAPs should be considered in older individuals and those who have diabetes or low HDL-C.

Inappropriate dose of nonvitamin-K antagonist oral anticoagulants: prevalence and impact on clinical outcome in patients with nonvalvular atrial fibrillation.

Limited real-world data are available regarding the outcome of patients treated with inappropriate dose of nonvitamin-K antagonist oral anticoagulants (NOACs). To assess the prevalence and factors associated with inappropriate dose prescription of NOACs and to evaluate adverse events that come from this inappropriate prescription. Single-center multidisciplinary registry including nonvalvular atrial fibrillation patients treated with NOACs. Based on guidelines criteria for dose reduction, two subcohorts were defined as treated with appropriate or inappropriate NOACs dose. Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. A total of 760 nonvalvular atrial fibrillation patients were included; 32% patients were treated with dabigatran, 34% with apixaban, 24% with rivaroxaban and 10% with edoxaban. An inappropriate dose was prescribed in 96 patients (12.6%), and in most cases (68%) it was too low. Rivaroxaban (15%) and apixaban (18.5%) were the most frequently prescribed with an inappropriate dose. Patients treated with an inappropriate dose were elderly people, with low-creatinine clearance value, who had experienced previous bleeding and with a high CHADS2 VASc score. In 2 years, a trend for higher numbers of thromboembolic events (5.2 vs. 3.3%, P = 0.348) and less major bleeding (2.1 vs. 4.2%, P = 0.316) has been observed in patients with inappropriate NOACs prescriptions. Nearly 13% of patients were treated with an inappropriate dose of NOACs, in this single-center study. A trend for higher numbers of thromboembolic events was observed in these patients. The results should be considered as hypothesis generating.

Nine-year trend of oral anticoagulant use in patients with embolic stroke due to nonvalvular atrial fibrillation.

BackgroundDirect oral anticoagulants (DOACs) are increasingly used as an alternative to warfarin in patients with nonvalvular atrial fibrillation (NVAF). However, whether there is sufficient prescription of oral anticoagulants (OACs) to decrease the incidence of embolic stroke remains unclear.Methods and ResultsWe conducted a retrospective observational study of patients hospitalized with ischemic stroke between January 1, 2010 and December 31, 2018. During the 8 years, the annual incidence ratio of embolic stroke to all ischemic strokes did not decrease over time (21‐33%) except for that in 2018. The proportion of OAC users did not also change over time (from 23% to 45% [overall 31%], P = .78). Among the OAC users, 19% patients were warfarin users, and 12% patients were DOAC users. In 73% of warfarin users, prothrombin time was subtherapeutic, whereas in 60% of DOAC users, the dose was adequately prescribed. OACs were prescribed more often in patients with high CHADS2 score than in those with low score (P = .01). The number of patients who had no medical history of a doctor visit before admission increased significantly in the recent period of 2015‐2018 (22% vs 8% in the previous period of 2010‐2014) (P = .01).ConclusionsThe incidence of embolic stroke patients without OACs did not decrease over time, and OACs in patients with NVAF have not been sufficient, even in DOAC era. In recent years, the incidence of undiagnosed AF has increased. To prevent embolic stroke, a correct AF diagnosis beforehand is important.

Demographic and clinical profile of cardioembolic stroke patients in Western Sydney.

Cardioembolism (CE) contributes to a large proportion of ischaemic stroke. To evaluate the demographic and clinical profile of CE stroke in Western Sydney. A retrospective analysis of ischaemic stroke patients presenting to Westmead Hospital (January-October 2016) was performed. Strokes were classified by TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria into different categories. Clinical and demographic data were collected on all stroke patients, and differences between CE and other stroke causes were identified. Two hundred and twenty-eight consecutive patients (70.9 years; 53% male) were identified. By TOAST criteria, 21 (9%) had large-artery atherosclerosis, 94 (41%) CE, 10 (5%) small-vessel disease, 2 (1%) other aetiology and 101 (44%) undetermined aetiology. A significant proportion of CE stroke patients had cardiovascular risk factors including hypertension (66%), hypercholesterolaemia (50%), diabetes (26%) and ischaemic heart disease (28%). The majority (81%) of patients with CE had atrial flutter/flutter. CE stroke, compared with other types of stroke, was more common in females (56 vs 41%, P = 0.022) and patients with CE stroke were more likely to have previous cerebral ischaemia (34 vs 21%, P = 0.026), suggesting increased recurrence in this group. Of the patients with atrial flutter/flutter (n = 56), the majority (87%) had a high CHA2 DS2 -VASC score (≥2); however, a significant proportion (55.4%) were not on anticoagulation. Cardioembolic stroke remains a significant burden in Western Sydney, and it is likely that a significant proportion may be preventable, as evidenced by the substantial presence of modifiable cardiovascular risk factors, and inadequate anticoagulation of patients with atrial arrhythmias.

Ischemic stroke and dose adjustment of oral Factor Xa inhibitors in patients with atrial fibrillation

BackgroundOral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation require dose adjustment based on certain clinical criteria, but the off-label use of the reduced doses is common.MethodsData from an observational registry including patients admitted with acute cerebral ischemia while taking oral Factor Xa inhibitors for atrial fibrillation between April 2016 and December 2018 were investigated. The dose regimen of the Xa inhibitor was classified as “appropriate”, “underdosed” and “overdosed” in conformity with the European Medicines Agency labelling. The effect of underdosing on the functional factor Xa plasma level on admission, the clinical stroke severity and the functional outcome after 3 months were investigated.Results254 patients with cerebral ischemia while on Factor Xa inhibitors were included. The dose regimen of the Factor Xa inhibitor was appropriate in 166 patients (65%), underdosed in 67 patients (26%) and overdosed in 21 patients (8%). Underdosing was associated with female sex, diabetes mellitus and higher CHA2DS2–Vasc scores. Underdosing independently predicted lower anti-Xa plasma levels on admission [median 69.4 ng/ml (IQR 0.0–121.6) vs. 129.2 ng/ml (65.5–207.2); p < 0.001], was associated with higher NIHSS scores on admission [median 5 (IQR 1–10) vs. 3 (1–7); p = 0.041] and worse functional outcome after 3 months (favorable outcome 26.9% vs. 46.9%; p = 0.025).ConclusionOne in three patients with ischemic stroke during treatment with oral Xa inhibitors used inappropriate dose regimens. Underdosing was associated with lower functional plasma levels, higher clinical stroke severity and worse functional outcome.

Impact of the Fibrosis-4 Index on Risk Stratification of Cardiovascular Events and Mortality in Patients with Atrial Fibrillation: Findings from a Japanese Multicenter Registry.

Background: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. Methods: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index < 1.75, n = 1022), second tertile (1.75 ≤ FIB4 index < 2.51, n = 1022), and third tertile (FIB4 index ≥ 2.51, n = 1023). Results: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p < 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p < 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31–2.25) and all-cause mortality (HR 1.43; 95% CI 1.06–1.95). Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p < 0.05), net reclassification improvement (all p < 0.001), and integrated discrimination improvement (all p < 0.001). A FIB4 index ≥ 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p < 0.001). Conclusions: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients.

Oral Anticoagulant Prescription Trends, Profile Use, and Determinants of Adherence in Patients with Atrial Fibrillation.

Data on oral anticoagulant (OAC) uptake and pattern of use are limited. Real-life data in patients with atrial fibrillation (AF) are important for understanding patient exposure. A cohort study of new OAC users was built to assess trends of drug use from 2011 to 2017, persistence rate, switching rate, adherence level, and predictors of adherence. We built a cohort using the Régie d'Assurance Maladie du Québec (RAMQ) and Med-Echo administrative databases of new adult OAC users within 1year following hospitalization with a diagnosis of AF. New users of OAC were defined as having no OAC claims in the year before cohort entry. We assessed trends of OAC use; persistence rate, defined as a gap between refills of no longer than two times the duration of the previous prescriptions; and adherence level, defined as the proportion of days covered (PDC) over a 1-year period following initiation. Predictors of nonadherence (PDC less than 80%) were analyzed using logistic regression models. The cohort consisted of 33,311 incident OAC users. Of total OAC claims, the proportions of warfarin claims decreased from 77.9% in 2011 to 12.7% in 2017, with direct oral anticoagulants (DOACs) accounting for 87.3% of claims, of which apixaban and rivaroxaban accounted for 60.1% and 23.4%, respectively, by the end of 2017. One year after OAC initiation, persistence rates ranged from 53% with warfarin to 77% with a high dose of apixaban. Approximately 75% of incident OAC users were considered "adherent" (PDC 80% or more), with a mean PDC of 95.6-98.1%, compared with "nonadherent," with a mean PDC varying between 43.1% and 50.7%. Older age, female sex, higher CHA2 DS2 -VASc score (to predict thromboembolic risk in AF), prior stroke, and treatment with chronic cardiovascular disease drugs were associated with high adherence levels. The clinical uptake of DOACs increased over time, accounting for 87.3% of prescriptions in 2017. In our study, 25% of new OAC users presented a low adherence level. Adherence to OACs remains a significant challenge in patients with AF.

Successful catheter ablation improves exercise tolerance in persistent atrial fibrillation patients, especially those with reduced ventricular contraction, preserved atrial function, or a high CHADS2 score

BackgroundIt has been reported that rhythm control for persistent atrial fibrillation (per-AF) patients by catheter ablation improves their exercise tolerance, subjective symptoms, and quality of life (QoL). However, clinical factors that can predict future improvement of exercise capacity after successful catheter ablation in per-AF patients are unclear. MethodsThis study consisted of 62 patients (mean age 65.6 ± 8.7 years, 77% males) with per-AF who underwent catheter ablation from June 2017 to May 2018. All patients were subjected to extended pulmonary vein isolation. Exercise tolerance was evaluated using a symptom-limited cardiopulmonary exercise test before and 3 months after catheter ablation. Primary endpoints were QoL measurements using an original questionnaire and functional assessments performed at 3 months. ResultsThe questionnaire revealed significant improvement in QoL after catheter ablation (minimal metabolic equivalents occurring symptoms: from 5.48 ± 1.14 to 5.64 ± 1.06; p = 0.01). Endurance exercise characteristics improved significantly after catheter ablation, demonstrated by a shift in anaerobic threshold (from 13.3 ± 3.0 to 15.2 ± 3.3 ml/kg/min; p < 0.001), peak oxygen uptake (from 19.1 ± 4.6 to 22.5 ± 5.0 ml/kg/min; p < 0.001), and minute ventilation vs carbon dioxide production slope (from 28.3 ± 6.1 to 25.7 ± 3.8; p < 0.001). Multivariate Cox regression analysis revealed that a decreased left ventricular ejection fraction, high left atrial appendage velocity, and high CHADS2 score were identified as independent predictors of anaerobic threshold and a peak value of oxygen uptake with more than 20% improvement. ConclusionsCatheter ablation for per-AF patients improves QoL and exercise tolerance. The effect was especially remarkable in patients with reduced ventricular function, those who had a preserved atrial function, or those at high risk of thromboembolism.

Current status of percutaneous coronary intervention in patients with atrial fibrillation: The Fushimi AF Registry

BackgroundAntithrombotic therapies that are optimal for atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI) have been studied but remain uncertain. We often encounter difficulties in choosing an appropriate antithrombotic therapy with antiplatelet agents after PCI in AF patients treated with oral anticoagulant due to a high CHADS2 score. Since there are no data on the incidences of PCI procedures in AF patients, we evaluated those incidences as well as the association between PCI and the CHADS2 score using data from the Fushimi AF Registry. MethodsThe Fushimi AF Registry is a community-based prospective cohort study of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 4325 patients, and the median follow-up was 3.6 (interquartile range: 1.9–5.9) years. ResultsThere were 143 PCI procedures performed in 122 patients during follow-up, and 28 (20%) were emergent ones. The crude incidence of PCI procedures was 9.36 per 1000 person-years. At 1 and 3 years, the cumulative incidences of PCI were 46 (1.1%) and 85 (2.4%), respectively. As for 4 age groups: <65 (n = 765), 65–75 (n = 1359), 75–85 (n = 1586), and 85≤ years (n = 615), the rates of PCI were 0.4%, 1.4%, 1.4%, and 0.6% at 1 year, and were 1.4%, 2.7%, 2.8%, and 1.6% at 3 years, respectively. The incidence of PCI procedures in patients with a CHADS2 score ≥2 (n = 2651, 61.3%) was higher than that in patients with a CHADS2 score ≤1 (n = 1674, 38.7%). Among the factors making up the CHADS2 score, only diabetes mellitus was associated with PCI procedures in patients with AF (hazard ratio, 1.95; 95% confidence interval, 1.34–2.83; p = 0.0005). ConclusionsAbout 1 in 100 AF patients underwent PCI annually, and patients with a CHADS2 score ≥2 were associated with higher incidences of PCI procedures.

Gastrointestinal bleeding in patients with atrial fibrillation treated with Apixaban or warfarin: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial

A history of gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) may impact decisions about anticoagulation treatment. We sought to determine whether prior GIB in patients with AF taking anticoagulants was associated with an increased risk of stroke or major hemorrhage. We analyzed key efficacy and safety outcomes in patients with prior GIB in ARISTOTLE. Centrally adjudicated outcomes according to GIB history were analyzed using Cox proportional hazards models adjusted for randomized treatment and established risk factors. A total of 784 (4.3%) patients had prior GIB events (321 [41%] lower, 463 [59%] upper); 215 (27%) occurred <1 year before study enrollment. Patients with prior GIB were older, had more comorbidities, and higher CHADS2 and HAS-BLED scores than those with no GIB. Major GIB occurred more frequently in those with prior GIB (lower: aHR 1.72, 95% CI 0.86-3.42; upper: aHR 3.13, 95% CI 1.97-4.96). This association with major GIB was more pronounced in patients with GIB <1 year before randomization versus no recent GIB (recent lower: aHR 2.58, 95% CI 0.95-7.01; recent upper: aHR 5.16, 95% CI 2.66-10.0). There was no association between prior GIB and risk of stroke/systemic embolism or all-cause death. In those with prior GIB, the apixaban versus warfarin relative risks for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding were consistent with the results of the overall trial. In patients with AF on oral anticoagulants, prior GIB was associated with an increased risk of subsequent major GIB but not stroke, intracranial bleeding, or all-cause mortality. For the key outcomes of stroke, hemorrhagic stroke, death, and major bleeding, we found no evidence that the treatment effect (apixaban vs. warfarin) was modified by a history of GIB.

Real-World Outcomes of Rivaroxaban Treatment in Patients with Both Nonvalvular Atrial Fibrillation and a History of Ischemic Stroke/Transient Ischemic Attack

Introduction: Prior stroke is a risk factor for stroke and bleeding during anticoagulation in patients with atrial fibrillation (AF). Although rivaroxaban is widely prescribed to reduce their risk of stroke in patients with nonvalvular AF (NVAF), the real-world evidence on rivaroxaban treatment is limited. We aimed to examine the outcomes of rivaroxaban treatment in NVAF patients with prior ischemic stroke/transient ischemic attack (TIA) by using the data of the Xarelto Post-Authorization Safety and Effectiveness Study in Japanese ­Patients with AF, a prospective, single-arm, observational study. Methods: The clinical outcomes of 9,578 patients who completed the 1-year follow-up were evaluated. Safety and effectiveness outcomes were compared between patients with and without prior ischemic stroke/TIA. Results: Among the patients, 2,153 (22.5%) had prior ischemic stroke/TIA. They were significantly older and had lower body weight, lower creatinine clearance, higher CHADS₂, CHA₂DS₂-VASc, and modified HAS-BLED scores as compared to those without prior ischemic stroke/TIA. Any bleeding (9.1 vs. 7.2 events per 100 patient-years), major bleeding (2.3 vs. 1.6 events per 100 patient-years), and stroke/non-central nervous system systemic embolism/myocardial infarction (3.4 vs. 1.3 events per 100 patient-years) were more frequent in patients with prior ischemic stroke/TIA. Stepwise regression analysis suggested that body weight of ≤50 kg and diabetes mellitus were predictive of major bleeding in patients with prior ischemic stroke/TIA. Conclusions: Safety and effectiveness event rates were higher in patients with prior ischemic stroke/TIA than those without. This might be explained by differences in several risk profiles including age, body weight, renal function, and risk scores such as CHADS₂ between the groups. Clinicaltrials.gov: NCT01582737.

P3755Left atrial enlargement as an independent risk factor for ischemic stroke in Japanese atrial fibrillation patients: pooled analysis of five major Japanese atrial fibrillation registries

Abstract Background Atrial fibrillation (AF) increases the risk of ischemic stroke. It remains unknown whether left atrial diameter determined by routine trans-thoracic echocardiography is a risk factor for ischemic stroke in non-valvular AF (NVAF) patients. Purpose The aim of this study is to investigate the impact of left atrial enlargement (LAE) on the incidence of ischemic stroke in a large-scale cohort of Japanese NVAF patients. Methods We combined the data of 5 major AF registries in Japan, J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku AF Registry. After excluding patients without echocardiographic data, 7,672 NVAF patients were analyzed in the present study (mean age, 69.3±12.3 years; mean CHADS2 score, 1.6±1.3). We compared clinical characteristics and the incidence of ischemic stroke between NVAF patients with LAE (left atrial diameter &gt;45 mm; LAE group) and those without (non-LAE group). Results The mean left atrial diameter was 43.1±8.6 mm, and the LAE group accounted for 40.0% (n=3,066) of the entire cohort. Compared with non-LAE group (60.0%, n=4,606), the LAE group was older (LAE vs. non-LAE; 70.3±12.0 vs. 68.0±12.5, p&lt;0.01), more often non-paroxysmal type (73.7% vs. 32.1%, p&lt;0.01), had higher CHADS2 (1.86±1.34 vs. 1.46±1.29, p&lt;0.01) and CHA2DS2-VASc (3.02±1.83 vs. 2.53±1.78, p&lt;0.01) scores, and more frequently received oral anticoagulant (72.9% vs. 55.0%, p&lt;0.01). During the median follow-up period of 774.5 days (interquartile range: 567–1466 days), ischemic stroke occurred in 241 patients (131 vs. 110 patients; 1.52 vs. 0.82 per 100 person-years). In Kaplan Meier analysis, LAE was associated with a higher incidence of ischemic stroke (unadjusted hazard ratio (HR): 1.83, 95% confidence interval (CI): 1.42–2.36; log rank p&lt;0.01) (Figure). LAE was independently associated with increased risk of ischemic stroke (adjusted HR: 1.63, 95% CI: 1.25–2.11; p&lt;0.01) after adjustment by the components of CHADS2 score and the use of oral anticoagulant, on multivariate Cox proportional hazard analysis. Conclusion In this large-scale cohort of Japanese patients with AF, LAE was an independent predictor of ischemic stroke, suggesting that this simple echocardiographic parameter could refine thromboembolic risk stratification of NVAF patients. Acknowledgement/Funding Japan Agency for Medical Research and Development, AMED

P3707CHA2DS2 VASC score as predictor of the incidence of stroke in patients with stable coronary artery disease and sinus rhythm in the long-term follow-up

Abstract Background Cerebral vascular disease and coronary artery disease (CAD) share risk factors. Our aim was to study CHA2DS2VASC score as predictor of stroke incidence in a sample of patients with sinus ryhtm and stable CAD (sCAD) during long term follow-up. Methods The CICCOR registry (“Chronic ischaemic heart disease in Cordoba”) is a prospective monocentric cohort study. Between February 2000 and January 2004 all patients with sCAD who attended two outpatient cardiology clinics in a city of the South of Spain were recruited. We analyzed the relationship between baseline CHA2DS2VASC score and the incidence of stroke in a sample of patients with sCAD without atrial fibrillation during long term follow-up. Patients without sinus rythm were excluded. Results 1268 patients with sCAD were recruited (median age 68±10 years, 73% male). 69 patients showed atrial fibrillation and were excluded. The median follow-up was 11.2 years (maximum follow-up of 17 years). During this period, only 2 patients were lost, and 136 patients (11.5% of the sample) suffered stroke. Baseline mean CHA2DS2 VASC score was 3.21. Most patients showed CHA2DS2 VASC score lower than 4 (81.4% of the sample). Higher CHA2DS2 VASC score at baseline was associated with higher risk of suffering stroke during follow-up (Hazard Ratio = 1.31 (1.16–1.48); p&lt;0.001). Mean results are shown in the table. Table 1 No stroke (n=1063) Stroke (n=136) Hazard ratio (CI 95%) p Sex male (%) 777 (88.8) 98 (11.2) High blood pressure (%) 561 (86.6) 86 (13.3) Diabetes mellitus (%) 317 (86.4) 50 (13.6) 75 years and older (%) 205 (83.7) 40 (16.3) Mean CHADS VASC score 3.17 3.55 1.31 (1.16–1.48) &lt;0.001 CHADS VASC score higher than 4 (%) 185 (84.1) 35 (15.9) 2.00 (1.33–3.01) 0.001 Stroke incidence according to CHADSVASC Conclusion Higher CHA2DS2 VASC score was significantly associated with higher stroke incidence during long term follow-up in this real-world sample of patients with sCAD in sinus rythm.

P3758Clinical characteristics and outcomes of atrial fibrillation patients with thrombocytopenia: the Fushimi AF Registry

Abstract Background Thrombocytopenia is sometimes found in routine blood tests and is reported as a risk factor of major bleeding events and incidence of all-cause death after percutaneous coronary intervention. However, the influence of thrombocytopenia on clinical outcomes in patients with atrial fibrillation (AF) remains unknown. Purpose We aimed to investigate relationship between baseline platelet count and clinical outcomes such as all-cause death, hospitalization for heart failure, and the major bleeding event in AF patients. Methods The Fushimi AF Registry was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. Follow-up data with baseline platelet counts were available in 4,179 patients from March 2011 to November 2018. We divided the entire cohort into 3 groups according to baseline platelet level: No thrombocytopenia (≥150,000/μL, n=3,323), Mild thrombocytopenia (100,000–149,999/μL, n=707), and Moderate/severe thrombocytopenia (≤99,999/μL, n=149). Results In the entire cohort, the mean age was 73 years, 40% were women, and the mean body weight and body mass index was 59 kg and 23.1 kg/m2, and the median platelet count were 192,000/μL (interquartile range 156,000 to 232,000/μL), respectively. Compared to No thrombocytopenia, patients with thrombocytopenia were older (No vs. Mild vs. Moderate/severe; 73.3 years vs. 76.5 years vs. 75.8 years, p&lt;0.0001), more likely to have heart failure (27.0% vs. 32.8% vs. 41.6%, p&lt;0.0001), more likely to have chronic renal disease (35.7% vs. 42.6% vs. 57.7%, p&lt;0.0001), and had higher CHADS2 score (2.05 vs. 2.17 vs. 2.34, p=0.0039) and CHA2DS2-VASc score (3.40 vs. 3.52 vs. 3.71, p=0.0416). Patients with thrombocytopenia had lower hemoglobin (13.0 vs. 12.8 vs. 11.6, p&lt;0.0001) than No thrombocytopenia. However, prevalence of previous major bleeding events was comparable between three groups (4.66% vs. 4.67% vs. 5.37%, p=0.92) On Kaplan-Meier analysis, the incidence of all-cause death was higher in Mild group (hazard ratio [HR] 1.51; 95% confidence interval [CI] 1.28–1.77) and Moderate/severe group (HR 2.97; 95% CI 2.28–3.80) than No group (Figure 1). The incidence of hospitalization for heart failure was higher in Mild group (HR 1.62; 95% CI 1.31–1.99) and Moderate/severe group (HR 2.64; 95% CI 1.76–3.81) than No group (Figure 2). The incidence of major bleeding event was higher in Mild group (HR 1.46; 95% CI 1.11–1.91) and Moderate/severe group (HR 2.45; 95% CI 1.41–3.91) than No group (Figure 3). Conclusion Thrombocytopenia in AF patients was associated with higher incidence of all-cause death, hospitalization for heart failure, and major bleeding event in the Fushimi AF Registry. Acknowledgement/Funding Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare,and Daiichi-Sankyo

CHADS2-VASC Score as a Predictor for Contrast Induced Nephropathy in Patient with Acute Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention

AbstractBackground: Ischaemic heart disease is the single most common cause of death and its frequency is increasing. Acute ST-Elevation Myocardial Infarction (STEMI) results from the sudden obstruction of a coronary artry. Acute kidney injury is a frequent complication among patients who undergo Primary Percutaneous Intervention (PCI) shown to be associ-ated with adverse outcomes. CHADS2 and the more recent CHA2DS2-VASc are two validated scores for predicting embolic/stroke risk in patients with non-valvular Atrial Fibril-lation (AF). The CHADS2-VASC score has been reported as risk factors for CIN and adverse cardiac events.Aim of the Study: The aim of this work is to evaluate CHA2DS2-VASC score as a predictor for Contrast-Induced Nephropathy (CIN) in patient with acute myocardial infarction treated with primary Percutaneous Coronary Intervention (PCI).Patient and Methods: The study included 100 patients presenting to Cardiology Department, Tanta University Hos-pital, diagnosed with as first time STEMI and underwent primary PCI. CHADS2-VASC score (age, sex, diabetes, hypertension, heart failure on admission, previous ischemic event, vascular event) was calculated for all patients. Serum creatinin level and effective Glomerular Filtration Rate (eGFR) were estimated for all patient before and 48h after PPCI.They were divided into into two groups: Group I: Those who developed CIN 48h after primary PCI (36%) and Group II: Those who did not (64%).Results: Patient who developed CIN had higher CHADS2- VASC score than who did not, mean ± SD value was 3.53±1.11 vs. 0.72±0.83, p-value 3 was independently associated with CIN development in patients with acute STEMI who were treated by PPCI. The more CHADS2-VASC score, the more risk for developing CIN after PPCI.

Use of CHADS2 and CHA2DS2-VASc scores to predict prognosis after stroke

IntroductionStroke is one of the most devastating neurological disorders. Currently, we don’t have an ideal score that predicts the prognosis of stroke patients. The CHADS2 and CHA2DS2-VASc scores are well-validated tools for the estimation of stroke risk in patients with atrial fibrillation. The purpose of this study was to investigate if these scores can predict the outcomes of all the patients who suffered an ischemic stroke regardless of atrial fibrillation. MethodsConsecutive patients that were admitted with an acute ischemic stroke were classified into subgroups according to pre-stroke CHADS2 and CHA2DS2-VASc scores and after 2 years the functional outcome, stroke recurrence, major cardiovascular events and mortality were assessed. ResultsAmong the 973 patients that were included in analysis, the mean age was 56.7 (SD 15.7) and 46.6% were female. There were 226 (23.2%), 365 (37.5%) and 382 (39.3%) patients with low, intermediate and high CHADS2 score, respectively. For CHADS2-VASc score there were 81 (8.3%), 268 (27.6%), and 624 (64.1%) patients with low, intermediate and high, respectively. Both high-risk scores were associated with middle-term poor functional outcome, stroke recurrence, major cardiovascular events and all-cause mortality. CHADS2 and CHA2DS2-VASc scores presented a high sensitivity and a high negative predictive value. CHA2DS2-VASc was more sensitive than CHADS2 score. ConclusionCHADS2 and CHA2DS2-VASc scores were both associated with stroke outcomes regardless of atrial fibrillation. These scores can be useful tools for the prognosis stratification of a patient with an ischemic stroke.