Gastrointestinal bleeding in elderly patients with atrial fibrillation: prespecified All Nippon Atrial Fibrillation in the Elderly (ANAFIE) Registry subgroup analysis.

Gastrointestinal (GI) bleeding control is critical in elderly patients with atrial fibrillation (AF) receiving oral anticoagulants (OAC). This subgroup analysis aimed to clarify the actual state and significance of GI bleeding in elderly non-valvular AF (NVAF) patients. We evaluated the incidence and risk factors of GI bleeding during the 2-year follow-up and examined the GI bleeding impact on mortality. Of the 32,275 patients in the ANAFIE Registry, 1139 patients (3.5%) experienced GI bleeding (incidence rate, 1.92 events per 100 person-years; mean follow-up, 1.88 years); 339 upper and 760 lower GI bleeding events occurred. GI bleeding risk factors included age ≥ 85 years, body mass index ≥ 25.0 kg/m2, prior major bleeding, hyperuricaemia, heart failure, P-glycoprotein inhibitor use, GI disease, and polypharmacy (≥ 5 drugs). No significant differences in GI bleeding risk were found between direct OAC (DOAC) vs warfarin users (adjusted hazard ratios [95% confidence interval], 1.01 [0.88-1.15]). The 1-year post-GI bleeding mortality rate was numerically higher in patients with upper (19.6%) than lower GI bleeding (8.9%). In elderly Japanese NVAF patients, this large-scale study found no significant difference in GI bleeding risk between DOAC vs. warfarin users or 1-year mortality after upper or lower GI bleeding.

Coronary events in elderly patients with non-valvular atrial fibrillation: a prespecified sub-analysis of the ANAFIE registry.

Real-world data on coronary events (CE) in elderly patients with atrial fibrillation (AF) are lacking in the direct oral anticoagulant era. This prespecified sub-analysis of the ANAFIE Registry, a prospective observational study in > 30,000 Japanese patients aged ≥ 75 years with non-valvular AF (NVAF), investigated CE incidence and risk factors. The incidence and risk factors for new-onset CE (a composite of myocardial infarction [MI] and cardiac intervention for coronary heart diseases other than MI), MI, and cardiac intervention for coronary heart diseases other than MI during the 2-year follow-up were assessed. Bleeding events in CE patients were also examined. Among 32,275 patients, the incidence rate per 100 patient-years was 0.48 (95% confidence interval (CI): 0.42-0.53) for CE during the 2-year follow-up, 0.20 (0.16-0.23) for MI, and 0.29 (0.25-0.33) for cardiac intervention for coronary heart diseases other than MI; that of stroke/systemic embolism was 1.62 (1.52-1.73). Patients with CE (n = 287) likely had lower creatinine clearance (CrCL) and higher CHADS2 and HAS-BLED scores than patients without CE (n = 31,988). Significant risk factors associated with new-onset CE were male sex, systolic blood pressure of ≥ 130 mmHg, diabetes mellitus (glycated hemoglobin ≥ 6.0%), CE history, antiplatelet agent use, and CrCL < 50 mL/min. Major bleeding incidence was significantly higher in patients with new-onset CE vs without CE (odds ratio [95% CI], 3.35 [2.06-5.43]). In elderly patients with NVAF, CE incidence was lower than stroke/systemic embolism incidence. New-onset CE (vs no CE) was associated with a higher incidence of major bleeding.Trial registration: UMIN000024006.

Idarucizumab for Emergency Reversal of the Anticoagulant Effects of Dabigatran: Final Results of a Japanese Postmarketing Surveillance Study.

INTRODUCTION: Idarucizumab, a monoclonal antibody fragment that rapidly reverses the anticoagulant effects of dabigatran, was approved in Japan in September 2016, at which time an all-case, postmarketing surveillance (PMS) study was initiated to collect data on idarucizumab in Japanese patients. Interim results were published previously, and the final results are reported herein. METHODS: This multicenter, open-label, uncontrolled, non-interventional PMS study was conducted in Japanese patients who received idarucizumab at the approved dose (2 × 2.5 g/50 ml) and had uncontrolled bleeding (group A) or required an emergency procedure (group B). The primary endpoint was the frequency of adverse drug reactions (ADRs). The secondary endpoint was the maximum extent of reversal of the anticoagulant effects of dabigatran, within 4 h of idarucizumab administration, based on activated partial thromboplastin time (aPTT). RESULTS: The final analysis included 804 patients. ADRs during the idarucizumab treatment and post-treatment periods were reported in 17 of 542 patients (3.1%) in group A and 12 of 240 patients (5.0%) in group B. Thrombotic events were reported in 22 patients (4.1%) in group A and 15 patients (6.3%) in group B, and hypersensitivity occurred in four (0.7%) and five patients (2.1%), respectively. Among 793 patients evaluated for effectiveness, 78 in group A and 26 in group B had aPTT data at baseline (immediately before idarucizumab administration) and within 4 h of idarucizumab administration; in these patients, median maximum percentage reversal within 4 h of idarucizumab administration was 100%. CONCLUSIONS: The final analysis from the PMS study confirms previous findings suggesting that idarucizumab can safely and effectively reverse the anticoagulant effects of dabigatran in Japanese patients in clinical practice. The results support the continued use of idarucizumab in Japan. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov (NCT02946931).

Atrial fibrillation is an irregular heart rhythm (arrhythmia), and the type of atrial fibrillation not caused by a heart valve problem is known as "non-valvular atrial fibrillation" or NVAF. People with NVAF have an increased risk of ischemic stroke, in which a blood clot (thrombus) blocks an artery in the brain. Drugs that inhibit blood clots, known as anticoagulants, are prescribed to people with NVAF to prevent ischemic stroke. Historically, warfarin has been one of the most prescribed anticoagulant drugs. However, a novel anticoagulant drug, known as dabigatran, has clinical advantages over warfarin and is approved in many countries for people with NVAF. People who take anticoagulants may experience life-threatening bleeding or need urgent surgery, and thus rapid and effective reversal of the anticoagulant effects is critical. The drug idarucizumab specifically binds to dabigatran to reverse its anticoagulant effects in people with uncontrolled bleeding or who require an urgent procedure. Idarucizumab was approved for use in Japan in September 2016. In Japan, drug companies are obligated to collect data after a new drug is launched as an approval condition, which is done through a postmarketing surveillance study. Here, we report the final results of a postmarketing surveillance study conducted between September 2016 and November 2020 to evaluate the safety and effectiveness of idarucizumab in Japanese patients receiving dabigatran. The results of our study show that idarucizumab can safely and effectively reverse the anticoagulant effects of dabigatran in Japanese patients, and support the continued use of idarucizumab in Japan in clinical practice.

The case of treatment for carotid web - Double-layer micromesh stent implantation in our hospital.

Background: A carotid web is a shelf-like structure on the posterior wall of the origin of the internal carotid artery, and it is believed to cause cerebral infarction due to thrombus formed by turbulent flow with stagnation of blood flow. Recently, it has been suggested that recurrent cerebral infarction cannot be prevented in patients with a symptomatic carotid web by conventional medical management alone. However, there is still no consensus on the treatment of carotid webs. Carotid artery stenting (CAS) with the CASPER stent (Microvention, Terumo, Tustin, CA, USA) was performed in six consecutive patients with symptomatic carotid webs, and the results are reported along with a review of the literature. Methods: Six consecutive patients with a diagnosis of internal carotid artery stenosis due to a carotid web on magnetic resonance imaging and digital subtraction angiography (DSA) were included in this study. All patients underwent dual antiplatelet therapy approximately 10 days before surgery and after 6 months, and then, a CASPER stent was implanted under general anesthesia. All patients were evaluated postoperatively by DSA 6 months after treatment. Results: In all patients, no in-stent stenosis was seen 6 months after the operation, and no symptomatic cerebral infarction occurred within 1 year after the procedure. Conclusions: CASPER stent implantation may be effective for treating carotid webs.

Strategy of cerebral endovascular treatment for cervical internal carotid artery stenosis with a persistent primitive hypoglossal artery.

Background: Persistent primitive hypoglossal artery (PPHA) is a rare residual arterial anastomosis. We placed a CASPER stent using Spider FX as an embolic protection device (EPD) in a patient with internal carotid artery (ICA) stenosis and PPHA. There are no reports of carotid artery stenting (CAS) using a CASPER stent for ICA stenosis with PPHA. We report the EPD strategy used in this case and the usefulness and precautions of CASPER stent insertion for cervical ICA stenosis in association with PPHA. Methods: A 9Fr sheath was placed in the right femoral artery and a 9Fr Branchor balloon guide catheter was guided to the common carotid artery. A Spider FX was placed proximal to the bifurcation of the ICA and the PPHA. A 10 mm × 20 mm CASPER stent was deployed at the site of the stricture with no postoperative ischemic complications. Results: There was no intra-stent occlusion, stenosis, or plaque protrusion immediately after surgery, and no postoperative ischemic complications were observed. Conclusion: CASPER stent deployment with the Spider FX in the ICA and PPHA bifurcation can be considered to be an effective treatment method for ICA stenosis associated with PPHA. However, care should be taken in selecting the appropriate EPDs and stents depending on the location of the stenosis and bifurcation of the PPHA.

Renal Function and Clinical Outcomes Among Elderly Patients With Nonvalvular Atrial Fibrillation From ANAFIE.

Background: Advancing age, decreasing renal function, and atrial fibrillation are strongly associated. Real-world evidence of direct oral anticoagulant (DOAC) use among elderly patients ≥75 years of age with nonvalvular atrial fibrillation and renal dysfunction is limited. Objectives: This study sought to assess 2-year outcomes and anticoagulant treatment, stratified by renal function. Methods: Enrolled patients were divided into 4 subgroups by creatinine clearance (CrCl) to determine the impact of renal dysfunction on clinical outcomes. Results: Of 32,275 patients, 26,202 with CrCl data were analyzed (median follow-up 2.00 [IQR: 1.92-2.00] years); 1.3% of patients had CrCl <15 mL/min, 10.7% had CrCl 15 to <30 mL/min, 33.4% had CrCl 30 to <50 mL/min, 35.8% had CrCl ≥50 mL/min, and 18.9% had unknown CrCl. Cumulative incidences of stroke/systemic embolic events, major bleeding, major plus clinically relevant nonmajor bleeding, cardiovascular death, all-cause death, and net clinical outcomes increased with decreasing CrCl. In multivariable Cox regression analysis, lower CrCl emerged as an independent risk factor for these clinical outcomes, except for major bleeding, compared with CrCl ≥50 mL/min. The effectiveness and safety of DOACs over warfarin were similar or better across 3 CrCl subgroups with CrCl 15 mL/min or more. DOAC use was associated with a lower risk of stroke/systemic embolic events, major bleeding, cardiovascular death, all-cause death, and net clinical outcome compared with warfarin in patients with CrCl 30 to <50 mL/min. Conclusions: Incidences of major clinical outcomes increased with decreasing renal function in elderly nonvalvular atrial fibrillation patients. DOACs were effective and safe even in patients with renal dysfunction (CrCl 15-<50 mL/min). (Prospective Observational Study in Late-Stage Elderly Patients with Non-Valvular Atrial Fibrillation: All Nippon AF In Elderly Registry [ANAFIE Registry]; UMIN000024006).

Relationship Between Direct Oral Anticoagulant Doses and Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- ANAFIE Registry Sub-Analysis.

BACKGROUND: This sub-analysis of the ANAFIE Registry, a prospective, observational study of >30,000 Japanese non-valvular atrial fibrillation (NVAF) patients aged ≥75 years, assessed the prevalence of direct oral anticoagulant (DOAC) under-dose prevalence, identified the factors of under-dose prescriptions, and examined the relationship between DOAC dose and clinical outcomes.Methods and Results: Patients, divided into 5 groups by DOAC dose (standard, over-, reduced, under-, and off-label), were analyzed for background factors, cumulative incidences, and clinical outcome risk. Endpoints were stroke/systemic embolic events (SEE), major bleeding, and all-cause death during the 2-year follow-up. Of 18,497 patients taking DOACs, 20.7%, 3.8%, 51.6%, 19.6%, and 4.3%, were prescribed standard, over-, reduced, under-, and off-label doses. Factors associated with under-dose use were female sex, age ≥85 years, reduced creatinine clearance, history of major bleeding, polypharmacy, antiplatelet agents, heart failure, dementia, and no history of catheter ablation or cerebrovascular disease. After confounder adjustment, under-dose vs. standard dose was not associated with the incidence of stroke/SEE or major bleeding but was associated with a higher mortality rate. Patients receiving an off-label dose showed similar tendencies to those receiving an under-dose; that is, they showed the highest mortality rates for stroke/SEE, major bleeding, and all-cause death. CONCLUSIONS: Inappropriate low DOAC doses (under- or off-label dose) were not associated with stroke/SEE or major bleeding but were associated with all-cause death.

Causes of Death in Elderly Patients With Non-Valvular Atrial Fibrillation　- Results From the ANAFIE Registry.

BACKGROUND: Previous studies on mortality in atrial fibrillation (AF) included a limited number of elderly patients receiving direct oral anticoagulants (DOACs). This subanalysis of the ANAFIE Registry evaluated 2-year mortality according to causes of death of elderly non-valvular AF (NVAF) patients in the DOAC era.Methods and Results: The ANAFIE Registry was a multicenter prospective observational study. Mean patient age was 81.5 years and 57.3% of patients were male. Of the 32,275 patients completing the study, 2,242 died. The most frequent causes of death were cardiovascular (CV) death (32.4%), followed by infection (17.1%) and malignancy (16.1%). Incidence rates of CV-, malignancy-, and infection-related death were 1.20, 0.60, and 0.63 per 100 person-years, respectively. Patients aged ≥85 years showed increased proportions of non-CV and non-malignancy deaths and a decreased proportion of malignancy deaths compared with patients aged <85 years. The incidence of death due to congestive heart failure/cardiogenic shock, infection, and renal disease was higher in patients aged ≥85 than those aged <85 years. Compared with warfarin, DOACs were associated with a significantly lower risk of death by intracranial hemorrhage, ischemic stroke, and renal disease. CONCLUSIONS: This subanalysis described the mortality according to causes of death of Japanese elderly NVAF patients in the DOAC era. Our results imply that a more holistic approach to comorbid conditions and stroke prevention are required in these patients.

Oral Anticoagulants in Very Elderly Nonvalvular Atrial Fibrillation Patients With High Bleeding Risks: ANAFIE Registry.

Background: Data on the effectiveness and safety of oral anticoagulant (OAC) agents in very elderly nonvalvular atrial fibrillation patients with high bleeding risk are lacking. Objectives: This study examined 2-year outcomes and effects of OAC agents among these patients using the ANAFIE (All Nippon Atrial Fibrillation in the Elderly) registry (N = 32,275) data. Methods: Patients were classified into high-risk (age: ≥80 years; CHADS2 score: ≥2; and presence of ≥1 bleeding risk factor: creatinine clearance of 15-30 mL/minute, prior bleeding at critical sites, body weight of ≤45 kg, or continuous antiplatelet use) and reference groups. Results: In the high-risk (n = 7,104) and reference (n = 25,171) group patients, 89.0% and 93.4%, respectively, used OAC agents. Of these, respectively, 30.1% and 24.2% used warfarin, and 58.9% and 69.1% used direct-acting OAC (DOAC) agents. Compared with the reference group, the high-risk group had higher incidences of stroke/systemic embolism, major bleeding, intracranial hemorrhage, gastrointestinal bleeding, cardiovascular events, and all-cause death. In the high-risk group, DOAC agent use vs nonuse of OAC agents was associated with reduced incidences of stroke/systemic embolism (HR: 0.53; 95% CI: 0.36-0.79) and all-cause death (HR: 0.65; 95% CI: 0.52-0.81) but not with major bleeding (HR: 1.09; 95% CI: 0.63-1.89). DOAC agents were superior to warfarin in effectiveness and safety. For high-risk patients, history of major bleeding, severe liver dysfunction, and falls within 1 year were independent risk factors for major bleeding. Conclusions: High-risk elderly nonvalvular atrial fibrillation patients had higher event incidences. DOAC agents were associated with reduced risk of stroke/systemic embolism and all-cause death vs nonuse of OAC agents or warfarin. (Prospective Observational Study in Late-Stage Elderly Patients With Nonvalvular Atrial Fibrillation [ANAFIE registry]; UMIN000024006).

Effect of Polypharmacy on Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- A Sub-Analysis of the ANAFIE Registry.

BACKGROUND: This All Nippon AF in the Elderly (ANAFIE) Registry sub-analysis evaluated the impact of polypharmacy on 2-year outcomes in a large, elderly (aged ≥75 years) Japanese population with non-valvular atrial fibrillation (NVAF).Methods and Results: The ANAFIE Registry was a multicenter, prospective, observational study with a 24-month follow-up period. Of 32,275 enrolled NVAF patients, 31,419 were grouped by the number of prescribed concomitant medications (other than oral anticoagulants [OACs]): 0-4 [38.8%], 5-8 [43.3%], and ≥9 [17.9%]). Patients receiving more concomitant medications were older, had poor renal function, and suffered more comorbidities than those receiving fewer concomitant medications. Several patient background factors, including diabetes mellitus, myocardial infarction, and chronic kidney disease, were significantly correlated with an increased number of concomitant medications. With increasing medications, OAC prescription rates decreased, but the warfarin prescription rate increased, and the cumulative incidence rates of stroke/systemic embolic events (SEE), major bleeding, gastrointestinal bleeding, fracture/falls, cardiovascular events, cardiovascular death, and all-cause death significantly increased (each, P<0.05). In multivariate analysis, increasing medications was independently associated with increases in these events, except for stroke/SEE. There were no significant interactions between the number of medications and anticoagulant treatment with direct OAC or warfarin concerning the incidence of these events. CONCLUSIONS: Polypharmacy was frequent among elderly patients with NVAF who were older with more comorbidities, and was independently associated with a higher incidence of extracranial events.

Unilateral agenesis of internal carotid artery with interparaclinoid and contralateral carotid-anterior cerebral artery anastomoses diagnosed by magnetic resonance angiography: a case report.

PURPOSE: Unilateral agenesis of the internal carotid artery (ICA) is a rare anatomical variant. We identified a case of unilateral ICA agenesis with interparaclinoid and contralateral carotid-ACA anastomoses. METHODS: A 65-year-old female with a long history of depressive episodes underwent MR imaging including MR angiography at National Hospital Organization Kyushu Medical Center. MR imaging was performed using a 3.0-T MR scanner to rule out vascular Parkinsonism, although drug-induced Parkinsonism was suspected from her medical history. RESULTS: The proximal left ICA was not visible on MR angiography, and an anterior communicating artery (ACoA) aneurysm was identified. The left middle cerebral artery was supplied from the right ICA via an interparaclinoid anastomosis. This interparaclinoid anastomosis showed no communication with the basilar, posterior communicating, or posterior cerebral arteries. A communicating artery connecting the interparaclinoid anastomosis and anterior cerebral artery (ACA) branched off from the presumed transition point between the interparaclinoid anastomosis and left ICA. Both right and left ophthalmic arteries (OAs) originated from the clinoid segment of the ICA. The communicating artery connecting the interparaclinoid anastomosis and ACA arose proximal to the left OA, and the communicating artery was identified as the carotid-ACA anastomosis. CONCLUSION: Neuroradiologists, physicians, and neurosurgeons need to be aware of this extremely unusual anatomical variant to determine appropriate treatment strategies in cases of aneurysmal growth or anterior cranial base surgery.

Effect of Cancer on Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- Substudy of the ANAFIE Registry.

BACKGROUND: Data on outcomes for patients with atrial fibrillation (AF) and active cancer are scarce. The effect of active cancer on thrombosis and bleeding risks in elderly (≥75 years) patients with non-valvular AF (NVAF) enrolled in the All Nippon AF In the Elderly (ANAFIE) Registry were prospectively analyzed.Methods and Results:In this subanalysis of the ANAFIE Registry, a prospective, multicenter, observational study conducted in Japan, we compared the incidence rates of clinical outcomes between active cancer and non-cancer groups. Relationships between primary outcomes and anticoagulation status were evaluated. Of the 32,725 patients enrolled in the Registry, 3,569 had active cancer at baseline; 92.0% of active cancer patients received anticoagulants (23.7%, warfarin; 68.2%, direct oral anticoagulants [DOACs]). Two-year probabilities of stroke/systemic embolic events (SEE) were similar in the cancer (3.33%) and non-cancer (3.16%) groups. Patients with cancer had greater incidences of major bleeding (2.86% vs. 2.04%), all-cause death (10.95% vs. 6.77%), and net clinical outcomes (14.63% vs. 10.00%) than those without cancer. In patients without cancer, DOACs were associated with a decreased risk of stroke/SEE, major bleeding, all-cause death, and net clinical outcome compared with warfarin. No between-treatment differences were observed in patients with active cancer. CONCLUSIONS: Active cancer had no effect on stroke/SEE incidence in elderly NVAF patients, but those with cancer had higher incidences of major bleeding events and all-cause death than those without cancer.

Background characteristics and anticoagulant usage patterns of elderly non-valvular atrial fibrillation patients in the ANAFIE registry: a prospective, multicentre, observational cohort study in Japan.

OBJECTIVE: To explore anticoagulant usage patterns stratified by stroke and bleeding risk in elderly patients with non-valvular atrial fibrillation (NVAF). DESIGN: Prospective, multicentre, observational cohort study. SETTING: The real-world All Nippon AF In the Elderly (ANAFIE) registry. PARTICIPANTS: Japanese patients aged ≥75 years with NVAF (n=32 726). OUTCOME MEASURES: The distribution of stroke and bleeding risk scores, and the selection of anticoagulant regimen for patients at high stroke and bleeding risk. RESULTS: Overall, 18 185 (55.6%) patients had a high risk of stroke (CHADS2 score ≥3). Of these, 12 561 (38.4% of the total ANAFIE population) had a low bleeding risk (HAS-BLED ≤2) and 5624 (17.2%) had a high bleeding risk (HAS-BLED ≥3). Significant differences were noted between the high versus low bleeding risk groups in sex, height, weight, systolic blood pressure and rates of abnormality of lipid metabolism, gastrointestinal disease, cerebrovascular disorders, chronic kidney disease, angina pectoris, respiratory disease, primary malignant tumour, dementia and fall history within the past year (all p<0.0001). Patients with high stroke and bleeding risks had a lower anticoagulant usage rate versus the low bleeding risk group, and 8.7% and 5.8%, respectively, were not receiving any anticoagulant (p<0.0001). Patients in the high bleeding risk group had a higher usage of warfarin versus the low bleeding risk group (p<0.0001); more patients (14.0%) in the high bleeding risk group receiving warfarin had time in the therapeutic range <40%, versus those in the low bleeding risk group (11.6%, p=0.0146). Direct-acting oral anticoagulants (DOACs) were used less in the high bleeding risk group, without notable differences in the DOAC dose distribution between the two groups. CONCLUSIONS: In elderly NVAF patients at high stroke risk, significant demographic and clinical differences were observed according to bleeding risk. Administration of low-dose DOACs was frequent, but the dose distribution was unaffected by bleeding risk. TRIAL REGISTRATION NUMBER: UMIN000024006 (http://www.umin.ac.jp/).

Carotid ultrasonography predicts collateral development following combined direct and indirect revascularization surgery in adult ischemic Moyamoya disease.

OBJECTIVE: The relationship between carotid ultrasonographic parameters and postoperative collateral development in adult ischemic moyamoya disease (MMD) patients who received combined direct and indirect revascularization surgery remains unclear. Herein, we investigated the postoperative changes in carotid ultrasonographic parameters in patients with adult ischemic MMD. METHODS: We studied 28 adult ischemic MMD patients (31 hemispheres) who underwent combined revascularization surgery. Patients underwent preoperative and postoperative (within 14 days and 3, 12, and 24 months after surgery) magnetic resonance imaging and carotid ultrasonography. We defined the hemisphere in which all signal intensities of the superficial temporal, middle meningeal, and deep temporal arteries were increased compared with that before surgery on magnetic resonance angiography as well-developed collateral establishment. RESULTS: Patients with good collateral establishment on MRA at 2-year after surgery had a lower external carotid artery (ECA) pulsatility index (PI) (P = 0.0413) and ECA/internal carotid artery (ICA) pulsatility index (PI) ratio (P = 0.0427) at 3-month post-operation. At 3-month post-operation, a cut-off ECA PI of 1.416 (sensitivity 40.0 %, specificity 92.3 %, area under the curve 0.7282, likelihood ratio 5.20, P = 0.0404) and ECA/ICA PI ratio of 0.8768 (sensitivity 50.0 %, specificity 92.31 %, area under the curve 0.7308, likelihood ratio 6.50, P = 0.0415) provided reliable values for good prediction of collateral development at 2 years after revascularization. CONCLUSION: ECA/ICA PI ratio and ECA PI at 3-month after surgery can be one of the indicators for predicting future well-developed neovascularization on MRA and better outcome in patients with adult ischemic MMD who received combined direct and indirect revascularization surgery.

Ischemic Stroke Caused by Carotid Stump at the Common Carotid Artery.

An 84-year-old man developed motor aphasia and right hemiparesis on postoperative day 1 after orchiectomy for suspected malignant lymphoma. He had a history of thoracic endovascular aortic repair for aortic aneurysm using a bypass graft from the right subclavian artery to the left common carotid artery (CCA); however, the graft had become occluded six months later. Brain magnetic resonance imaging revealed acute cerebral infarctions in the left frontal lobe. Carotid ultrasonography revealed a stump at the left CCA, just below the bifurcation, formed by the occluded graft with an oscillating thrombus. This case was rare in that a CCA stump was identified as the embolic source of ischemic stroke.

Incidence Rates of Bleeding and Emergency Surgery Due to Trauma or Fracture Among Japanese Patients with Non-valvular Atrial Fibrillation Receiving Oral Anticoagulation Therapy.

INTRODUCTION: In patients with nonvalvular atrial fibrillation (NVAF) receiving oral anticoagulants (OACs), reversal of coagulopathy can be achieved with specific reversal drugs such as idarucizumab, which is indicated for use in patients treated with dabigatran for cases of life-threatening or uncontrolled bleeding or during emergency procedures that may cause serious bleeding. This study examined the incidence rate (IR) of emergency surgeries and major bleeding episodes associated with fractures and trauma in Japanese patients with NVAF receiving OACs. METHODS: This retrospective, non-interventional analysis of health insurance claims was conducted using data from 62,888 OAC-naive adult patients with NVAF who initiated dabigatran, warfarin, apixaban, rivaroxaban, or edoxaban between March 2011 and June 2016. The primary endpoint was overall IR of emergency surgery or major bleeding due to fracture or trauma. RESULTS: Overall IR of emergency surgery or major bleeding due to fracture or trauma considering outcomes until OAC discontinuation was 0.489 per 100 patient-years (PY) (95% confidence interval [CI] 0.406-0.572). Considering first OAC exposure only, the IR was 0.483 per 100 PY (95% CI 0.394-0.573). Emergency surgery/major bleeding events due to fracture or trauma was highest in those aged ≥ 75 years (0.611 per 100 PY [95% CI 0.481-0.741]). CONCLUSIONS: Fewer than one in 200 patients per year with NVAF receiving OACs experience emergency surgeries and major bleeding episodes associated with fractures and trauma; however, the IR of these events is markedly higher in patients of advanced age. TRIAL REGISTRATION: ClinicalTrials.gov 207, NCT03254147.

Patients with an abnormal heart rhythm (nonvalvular atrial fibrillation [NVAF]) have a higher risk of blood clots and stroke (which is when the blood supply to part of the brain is blocked). To reduce these risks, patients can take anticoagulants that slow or prevent the formation of blood clots. However, if the patient needs major emergency surgery or has a severe injury, the anticoagulants can increase their risk of bleeding, which can sometimes be life-threatening. There are drugs (e.g., idarucizumab) that can be used to reverse the effects of anticoagulants in this type of emergency. What we don't know is how many NVAF patients in Japan who are on anticoagulants have emergency surgeries or major bleeding after an injury, and therefore may require a reversal drug. The authors looked at Japanese health insurance claim data from 62,888 adult patients with NVAF who started taking an anticoagulant. They found that, annually, approximately 0.5% of the patients had emergency surgery or a major bleed associated with a fracture or injury. In very elderly patients (aged at least 75 years), the annual percentage was approximately 0.6%, which was almost double the annual percentage in patients aged less than 65 years. The authors concluded that, even though the number of people requiring a reversal agent are quite small, it is important to have an effective reversal agent for patients on anticoagulants, particularly older patients.

Idarucizumab for Emergency Reversal of Anticoagulant Effects of Dabigatran: Interim Results of a Japanese Post-Marketing Surveillance Study.

INTRODUCTION: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran, and it was approved in Japan in September 2016. An all-case post-marketing surveillance is ongoing to collect data in Japanese patients treated with idarucizumab who had serious bleeding (Group A) or required an urgent procedure (Group B). METHODS: The primary endpoint was the incidence of adverse drug reactions (ADRs). The secondary endpoint was the maximum extent of reversal of the anticoagulant effect of dabigatran based on activated partial thromboplastin time (aPTT) within 4 h after idarucizumab administration. RESULTS: This interim analysis included 262 patients who received idarucizumab. Eighteen patients (6.9%) experienced ADRs within 4 weeks. The reversal effect of idarucizumab based on aPTT within 4 h after idarucizumab administration was assessed in 30 patients and the median maximum percentage reversal was 100%. In Group A, the median time to bleeding cessation in patients without intracranial bleeding was 3.3 h. In Group B, normal intraoperative hemostasis was reported in 63 patients (72.4%). CONCLUSIONS: The results of this interim analysis suggest that idarucizumab is safe and effective for the reversal of dabigatran in Japanese patients in a real-world setting, and support the continued use of idarucizumab. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02946931.

Management of Antithrombotic Agents During Surgery or Other Kinds of Medical Procedures With Bleeding: The MARK Study.

Background Optimal management of antithrombotic agents during surgery has yet to be established. We performed a prospective multicenter observational study to determine the current status of the management of antithrombotic agents during surgery or other medical procedures with bleeding (MARK [Management of Antithrombotic Agents During Surgery or Other Kinds of Medical Procedures With Bleeding] study) in Japan. Methods and Results The participants were 9700 patients who received oral antithrombotic agents and underwent scheduled medical procedures with bleeding at 59 National Hospital Organization institutions in Japan. Primary outcomes were thromboembolic events, bleeding events, and death within 2 weeks before and 4 weeks after the procedures. We investigated the relationships between each outcome and patient demographics, comorbidities, type of procedure, and management of antithrombotic therapy. With respect to the periprocedural management of antithrombotic agents, 3551 patients continued oral antithrombotic agents (36.6%, continuation group) and 6149 patients discontinued them (63.4%, discontinuation group). The incidence of any thromboembolic event (1.7% versus 0.6%, P<0.001), major bleeding (7.6% versus 0.4%, P<0.001), and death (0.8% versus 0.4%, P<0.001) was all greater in the discontinuation group than the continuation group. In multivariate analysis, even after adjusting for confounding factors, discontinuation of anticoagulant agents was significantly associated with higher risk for both thromboembolic events (odds ratio: 4.55; 95% CI, 1.67-12.4; P=0.003) and major bleeding (odds ratio: 11.1; 95% CI, 2.03-60.3; P=0.006) in procedures with low bleeding risk. In contrast, heparin bridging therapy was significantly associated with higher risk for both thromboembolic events (odds ratio: 2.03; 95% CI, 1.28-3.22; P=0.003) and major bleeding (odds ratio: 1.36; 95% CI, 1.10-1.68; P=0.005) in procedures with high bleeding risk. Conclusions Discontinuation of oral antithrombotic agents and addition of low-dose heparin bridging therapy appear to be significantly associated with adverse events in the periprocedural period.

[Case report: transient ischemic stroke caused by internal carotid artery occlusion due to compression by pituitary apoplexy and hemodynamic mechanism].

An 87-year-old blind man was admitted due to repeatedly disturbed consciousness and fever. Brain CT showed a pituitary tumor with a hematoma and an occlusive lesion of the right internal carotid artery. He experienced consciousness disturbance and left limb weakness with hypotension for a few minutes on the day of admission. We considered pituitary apoplexy caused adrenal failure with hypotension and transient ischemic attack (TIA) induced by a hemodynamic mechanism. An increased dose of hydrocortisone improved the fever and hypotension, and resolved consciousness disturbance. This is a unique example of TIA caused by the occlusive lesion of the internal carotid artery compressed as a result of pituitary apoplexy and a hemodynamic mechanism.

Association of CYP2C19 Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke.

BACKGROUND: CYP2C19variants are associated with the antiplatelet effects of clopidogrel against recurrent cardiovascular events. However, it remains unknown whether the elapsed time from stroke onset affects the relationship between the genetic variants and such events. To address this, we conducted a prospective cohort study to determine the effect ofCYP2C19variants on clinical outcomes in the chronic phase.Methods and Results:In total, 518 Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Patients were classified into 3 clopidogrel-metabolizing groups according toCYP2C19genotype: extensive metabolizer (EM:*1/*1), intermediate metabolizer (IM:*1/*2or*1/*3), and poor metabolizer (PM:*2/*2,*2/*3, or*3/*3). Antiplatelet effects of clopidogrel were assessed by adenosine diphosphate (ADP)-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. The endpoint was composite cerebrocardiovascular events (CVEs). In 501 successfully followed-up patients, the median time from index stroke to enrollment was 181 days. There were 28 cardiovascular and 2 major bleeding events. There were no significant differences in the rates of cardiovascular events among the groups. CONCLUSIONS: Despite associations betweenCYP2C19variants and on-clopidogrel platelet reactivity, there was no significant difference in rates of CVEs in the chronic stroke phase among the 3 clopidogrel-metabolizing groups ofCYP2C19variants.