Purpose
Antiplatelet therapy (APT) is challenging in patients taking oral anticoagulants (OACs) for nonvalvular atrial fibrillation (NVAF) with concomitant atherosclerotic diseases. We scrutinized ...the generalizability of recent randomized clinical trials showing OAC use alone was superior to OAC plus antiplatelet use in patients with NVAF and coronary artery diseases (CAD).
Methods
We conducted a historical multicenter registry at 71 centers in Japan. The inclusion criterion was taking OACs for NVAF. The exclusion criteria were mechanical heart valves or history of pulmonary thrombosis or deep vein thrombosis. Consecutive patients (N = 7826) were registered in February 2013 and were followed until February 2017. The co‐primary endpoints were ischemic events and major bleedings. Secondary endpoints were ischemic stroke, hemorrhagic stroke, and all‐cause mortality.
Results
The mean patient age was 73 years; 67% were men. Antiplatelets were administered in 25% of patients and 27% had history of CAD. Cumulative incidences of ischemic events and major bleedings at 4 years were 5.9% and 9.6% in the APT group and 5.3% and 7.0% in the No‐APT group, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals CIs) of the APT group for ischemic events and major bleedings were 1.12 (0.84–1.49) and 1.26 (1.01–1.57), respectively. The adjusted HRs (95% CIs) for ischemic stroke, hemorrhagic stroke, and all‐cause mortality were 1.16 (0.86–1.57), and 1.31 (0.70–2.48), and 1.02 (0.82–1.26), respectively.
Conclusions
APT in patients taking OACs for NVAF did not prevent ischemic events but significantly increased major bleedings in the real‐world setting.
Outside of clinical trials, the prophylactic effect of dihydropyridine calcium channel blockers (CCBs) on ischemic events in patients with nonvalvular atrial fibrillation (NVAF) has not been ...confirmed. We compared the effect of dihydropyridine CCBs on ischemic events in anticoagulated NVAF patients. We conducted a multicenter historical cohort study at 71 centers in Japan. The inclusion criterion was taking vitamin K antagonists for NVAF. The exclusion criteria were mechanical heart valves and a history of pulmonary thrombosis or deep vein thrombosis. Consecutive patients (N = 7826) were registered in February 2013 and were followed until February 2017. The primary outcomes were ischemic events and ischemic strokes; the secondary outcomes were all-cause mortality, major bleeding, and hemorrhagic strokes. The mean patient age was 73 years old, and 67% of the patients were male. Seventy-eight percent of the patients had hypertension, and dihydropyridine CCBs were used by 2693 (34%) patients (CCB group). The cumulative incidences of ischemic events and ischemic strokes at 4 years in the CCB and No-CCB groups were 5.9% vs. 5.2% and 5.6% vs. 4.8%, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals CIs) of the CCB group for ischemic events and ischemic strokes were 1.22 (0.95-1.57) and 1.32 (1.02-1.71), respectively; the adjusted HRs (95% CIs) of the CCB group for all-cause mortality, major bleeding, and hemorrhagic strokes were 0.85 (0.69-1.04), 1.12 (0.92-1.35), and 1.08 (0.62-1.88), respectively. Dihydropyridine CCB use by anticoagulated NVAF patients significantly increased ischemic strokes in a real-world setting.
In conjunction with recent advancements in machine learning (ML), such technologies have been applied in various fields owing to their high predictive performance. We tried to develop prehospital ...stroke scale with ML. We conducted multi-center retrospective and prospective cohort study. The training cohort had eight centers in Japan from June 2015 to March 2018, and the test cohort had 13 centers from April 2019 to March 2020. We use the three different ML algorithms (logistic regression, random forests, XGBoost) to develop models. Main outcomes were large vessel occlusion (LVO), intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral infarction (CI) other than LVO. The predictive abilities were validated in the test cohort with accuracy, positive predictive value, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and
F
score. The training cohort included 3178 patients with 337 LVO, 487 ICH, 131 SAH, and 676 CI cases, and the test cohort included 3127 patients with 183 LVO, 372 ICH, 90 SAH, and 577 CI cases. The overall accuracies were 0.65, and the positive predictive values, sensitivities, specificities, AUCs, and
F
scores were stable in the test cohort. The classification abilities were also fair for all ML models. The AUCs for LVO of logistic regression, random forests, and XGBoost were 0.89, 0.89, and 0.88, respectively, in the test cohort, and these values were higher than the previously reported prediction models for LVO. The ML models developed to predict the probability and types of stroke at the prehospital stage had superior predictive abilities.
Background and aims
The association between body mass index (BMI) and clinical outcomes of patients with non-valvular atrial fibrillation (NVAF) taking oral anticoagulants (OACs) are controversial, ...and we thus analyzed the large registry data to elucidate them.
Methods and results
We conducted a historical cohort study at 71 centers in Japan and included outpatients with NVAF taking vitamin K antagonists (VKAs). Physicians in charge could change VKAs to direct OACs based on their judgement during follow-up period. We categorized patients into four BMI groups (kg/m
2
): underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30), and obese (30 ≤ BMI). The effects of each BMI group relative to the normal weight group on clinical outcomes consisting of all-cause death, ischemic events, and bleeding events were estimated using Cox proportional hazard models adjusting for potential confounders. We also constructed restricted cubic spline regression model adjusted by multivariable Cox proportional hazard models. We included 6927 patients consisting of an underweight (
n
= 386), normal weight (
n
= 3785), overweight (
n
= 2174), and obese (
n
= 582) groups. The median follow-up period was 3.9 years. In the underweight group, the adjusted hazard ratios (HRs) for all-cause death and ischemic events were 1.75 (1.30–2.34) and 1.61 (1.04–2.50). The HR for all-cause death was 0.63 (0.49–0.82) in the overweight group. Restricted cubic spline regression models confirmed that lower BMI showed significantly higher risks for all-cause death and ischemic events.
Conclusion
Among NVAF patients taking OACs, underweight patients had higher risks of all-cause death and ischemic events than other patients. Overweight patients had lower risk of all-cause death.
Prehospital prediction models to estimate the likelihood of several types of stroke (large vessel occlusion LVO, intracranial hemorrhage ICH, and subarachnoid hemorrhage SAH, and other types of ...stroke) should be useful to transfer those with suspected stroke to appropriate facilities. We recently reported Japan Urgent Stroke Triage (JUST) score with 21 items had excellent predictive abilities, and we further tried to simplify the score with parsimonious items and comparable predictive abilities.
We conducted historical and prospective multicenter cohort studies at 8 centers from June 2015 to March 2018. We developed the prediction rules with select variables from JUST score for LVO, ICH, SAH and other types of stroke in 2236 patients with suspected stroke in historical derivation cohort. We validated the developed prediction rules in 964 patients in prospective validation cohort.
There were 1150 stroke, including 235 LVO, 352 ICH, 107 SAH and 456 other types of stroke in the derivation cohort. We developed the scores with 7 items (high blood pressure, arrhythmia, conjugate deviation, headache, dysarthria, disturbance of consciousness, paralysis of upper limbs) and the developed scores had area under the receiver-operating curve (AUC) of 0.84 for any type of stroke, 0.89 for LVO, 0.79 for ICH, and 0.90 for SAH in the derivation cohort. There were 490 stroke, including 102 LVO, 138 ICH, 28 SAH and 222 other types of stroke in the validation cohort. The scores well discriminated these strokes in the validation cohort (AUC of 0.76 for any type of stroke; 0.81 for LVO, 0.73 for ICH, and 0.85 for SAH).
The simplified 7-item JUST (JUST-7) score had good predictive ability and can help healthcare providers to estimate the likelihood of different types of stroke and decide the referral hospital.
The effects of statins in patients with non-valvular atrial fibrillation (NVAF) taking oral anticoagulants (OACs) are not well-studied. This study was a historical multicenter registry of patients ...with NVAF taking OACs in Japan.
We excluded those patients with mechanical heart valves or a history of pulmonary or deep vein thrombosis. Overall, 7826 patients were registered on 26 February 2013 and followed until 25 February 2017. We compared those with versus without statin treatment (statin vs. no-statin groups) for the primary outcome of major bleeding and secondary outcomes of all-cause mortality, ischemic events, hemorrhagic stroke, and ischemic stroke.
Statins were administered in 2599 (33%) patients. The statin group was more likely to have paroxysmal AF (37% vs. 33%; p = 0.0003), hypertension (84% vs. 76%; p < 0.0001), diabetes mellitus (41% vs. 27%; p < 0.0001), and dyslipidemia (91% vs. 30%; p < 0.0001) than the no-statin group. The cumulative incidence of major bleeding was 6.9% and 8.1% (p = 0.06). The adjusted hazard ratio HR (95% confidence interval CI) of the statin group for major bleeding was 0.77 (0.63-0.94) compared with the no-statin group. The adjusted HR (95% CI) for all-cause mortality, ischemic events, hemorrhagic stroke, and ischemic stroke were 0.58 (0.47-0.71), 0.77 (0.59-0.999), 0.85 (0.48-1.50), and 0.79 (0.60-1.05), respectively.
Statins significantly reduced the risk of major bleeding, all-cause mortality, and ischemic events in patients with NVAF taking OACs. Their additive benefits should be considered in routine practice and thus be further researched.
An 88-year-old woman was transported to our hospital two days prior because of unconsciousness and headache. She showed mild unconsciousness (Japan Coma Scale: 3) and hypertension (261/127 172 mmHg), ...and head MRI revealed high-intensity area at the brain stem and bilateral posterior white matter. She was diagnosed with posterior reversible encephalopathy syndrome (PRES) and administered anti-hypertension therapy, which cured her unconsciousness on day 4. For treating renal failure, a diuretic drug was administered. On day 8, head MRI showed improvement of PRES; however, new cerebral infarction was also found at the bilateral hemisphere watershed area. We decreased the diuretic drug to increase the cerebral blood flow, and no new neurological deficits emerged. In cases of PRES induced by hypertension, the lowering of blood pressure is crucial, but the risk of hemodynamic infarction caused by too rapid lowering of blood pressure must be considered. We should explain the possibility of developing hemodynamic infarction to the elderly in advance.
Background
Anemia is encountered in patients with nonvalvular atrial fibrillation (NVAF) on oral anticoagulants (OACs) but the prognostic impact was not well scrutinized in real‐world settings.
...Methods
We conducted a historical multicenter registry of patients with NVAF taking OACs at 71 centers in Japan. Those with mechanical heart valves or a history of pulmonary thrombosis or deep venous thrombosis were excluded. Anemic patients were divided into three groups of hemoglobin (Hb) level: moderate/severe (Hb < 11.0 g/dL), mild (men: Hb of 11.0–12.9 g/dL; women: Hb of 11.0–11.9 g/dL), and no anemia. The endpoints included major bleeding, hemorrhagic stroke, ischemic events, ischemic stroke, and all‐cause mortality.
Results
Among 7558 consecutive patients (mean age, 73 years; men 67%) registered in February 2013 and followed until February 2017, 2100 (28%) patients had anemia. The anemic patients were older (moderate/severe: 79 years; mild: 77 years; no anemia: 71 years, p < .001), and HAS‐BLED score was significantly higher in the anemic patients (p < .001). The cumulative incidences at 4 years of major bleeding in moderate/severe, mild, and no anemia group, were 14.9%, 10.7%, and 6.4%, respectively. The adjusted hazard ratios (HRs) (95% confidential intervals (CIs)) of major bleeding of moderate/severe and mild anemia group were 1.96 (1.49–2.58) and 1.48 (1.17–1.87) compared to no anemia group. The adjusted HRs (95% CIs) for ischemic events were 0.63 (0.39–0.99) and 1.03 (0.76–1.39).
Conclusions
The severity of anemia in the patients with NVAF on OACs was associated with major bleeding.
Anemia was frequently encountered in patients with NVAF on OACs in daily clinical practice and significantly associated with the incidence of major bleeding and all‐cause mortality, but not with the incidence of ischemic events or strokes. Anemic status should be carefully monitored for such patients.
ObjectivesTo explore the awareness and practice of clinical research integrity among Japanese physicians.DesignA nationwide cross-sectional study conducted in March 2020.SettingAll hospitals in ...Japan.ParticipantsPhysicians aged <65 years who work at hospitals participated in clinical research over the past 5 years. The sample was stratified according to geographical location and subspecialty, and 1100 physicians were proportionally selected.Primary and secondary outcome measuresKnowledge and awareness of research integrity.ResultsAmong the 1100 participants, 587 (53%) had the experience of being the first author, 299 (27%) had been co-authors only and 214 (19%) had no authorship. A total of 1021 (93%) had experienced learning research integrity, and 555 (54%) became aware of research integrity. The experience of learning about research integrity was highest among those with first authorship (95%) and lowest among those without authorship (89%) (p=0.003). The majority of participants learnt about research integrity for passive reasons such as it being ‘required by the institution’ (57%) or it being ‘required to obtain approval of institutional review board (IRB)’ (30%). Potentially inappropriate research behaviours were observed in participants, with 11% indulging in copying and pasting for writing the paper, 11% for gifted authorship and 5.8% for the omission of IRB approval. Factors significantly associated with copying and pasting were being below 40 years old (OR: 1.84; 95% CI: 1.05 to 3.26), being the first presenter (OR: 1.64; 95% CI: 1.05 to 2.57) or having passive reasons for learning research integrity (OR: 2.96; 95% CI: 1.57 to 5.59). Furthermore, gifted authorship was significantly associated with being a co-author only (OR: 1.84; 95% CI: 1.18 to 2.87) and having passive reasons for learning about research integrity (OR: 1.79; 95% CI: 1.03 to 3.12).ConclusionsMost physicians conducting clinical research have learnt about research integrity, but potentially inappropriate research behaviours are associated with passive reasons for learning.
We investigated the association between current smoking and clinical outcomes in patients with atrial fibrillation (AF) prescribed vitamin K antagonist (VKA).
We conducted a retrospective study at 71 ...centers in Japan. The inclusion criterion was taking a VKA for AF. Exclusion criteria were mechanical heart valves or history of pulmonary thrombosis or deep vein thrombosis. Consecutive patients were registered in February 2013 and followed until February 2017. The primary outcomes included ischemic events and major bleedings. The secondary outcomes were ischemic stroke, hemorrhagic stroke, and all-cause mortality.
A total of 7826 patients were included, with a mean age of 73 years; 5274 (67%) were men. The adjusted hazard ratios (HRs; 95% confidence intervals CIs) of current smokers relative to non–current smokers for ischemic events and major bleedings were 1.64 (1.05–2.57) and 1.09 (0.72–1.65), respectively. The adjusted HRs (95% CIs) of current smokers relative to non–current smokers for ischemic stroke, hemorrhagic stroke, and all-cause mortality were 1.65 (1.03–2.64), 0.52 (0.12–2.15), and 1.26 (0.83–1.92), respectively.
There were significant associations between current smoking and ischemic events or ischemic stroke in patients with AF on VKA.
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