Publications

TCTR20180711003.

Intracerebral haemorrhage (ICH) is a life-threatening emergency, the incidence of which has increased in part due to an increase in the use of oral anticoagulants. A blood-fluid level within the haematoma, as revealed by computed tomography (CT), has been suggested as a marker for oral anticoagulant-associated ICH (OAC-ICH), but the diagnostic specificity and prognostic value of this finding remains unclear. In 855 patients with CT-confirmed acute ICH scanned within 48 h of symptom onset, we investigated the sensitivity and specificity of the presence of a CT-defined blood-fluid level (rated blinded to anticoagulant status) for identifying concomitant anticoagulant use. We also investigated the association of the presence of a blood-fluid level with six-month case fatality. Eighteen patients (2.1%) had a blood-fluid level identified on CT; of those with a blood-fluid level, 15 (83.3%) were taking anticoagulants. The specificity of blood-fluid level for OAC-ICH was 99.4%; the sensitivity was 4.2%. We could not detect an association between the presence of a blood-fluid level and an increased risk of death at six months (OR = 1.21, 95% CI 0.28-3.88, p = 0.769). The presence of a blood-fluid level should alert clinicians to the possibility of OAC-ICH, but absence of a blood-fluid level is not useful in excluding OAC-ICH.

Female sex has been suggested as a risk modifier for stroke in patients with atrial fibrillation (AF) with comorbid prevalent stroke risk factors. Management has evolved over time towards a holistic approach that may have diminished any sex difference in AF-related stroke. In a nationwide cohort of AF patients free from oral anticoagulant treatment, we examine the time trends in stroke risk overall and in relation to risk differences between male and female patients. Here we show that among 158,982 patients with AF (median age 78 years (IQR: 71 to 85); 52% female) the 1-year thromboembolic risk was highest between 1997-2000 with a risk of 5.6% and lowest between 2013-2016 with a risk of 3.8%, declining over the last two decades. The excess stroke risk for female vs male patients has also been declining, with risk-score adjusted relative risk estimates suggesting limited sex-difference in recent years.

CAs identified four statistically driven groups of CRT recipients, with specific clinical phenotypes and associated with different risks for all-cause death.

The trajectory changes of ApoAI levels significantly influences MACE risk during long-term follow-up, particularly in the low-stable and J-shaped trajectories. Dynamic monitoring of ApoAI may serve as a valuable tool for early risk stratification in high-risk populations, facilitating more individualised interventions.

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

Background: The worldwide prevalence of atrial fibrillation (AF) continues to grow with approximately 60 million cases each year. Aim: To understand demographic and clinical attributes of patients receiving adequate DOAC (direct oral anticoagulant) treatment, DOAC undertreatments, or no OAC (oral anticoagulant) treatments, thus providing valuable perspectives into the current landscape of stroke prevention in AF within the UK. Methods: We used the Clinical Practice Research Datalink (CPRD) Aurum database from January 2020 to March 2021 for this retrospective observational study. Patients’ characteristics from various cohorts (standard dose [SD], low dose [LD] per label, LD inconsistent per label prescribing, and untreated) were evaluated based on OAC treatment. Duration of index OAC treatment, time to discontinuation and incidence rates across OAC treated cohorts were assessed. A machine learning method (Elastic Net) identified factors associated with being undertreated or untreated. Results: The final sample included 13,341 patients (mean age 78.5 and female 47%). Within a 180-day timeframe post-diagnosis, 76% of patients received OAC treatment, while 24% did not receive any OAC therapy. Among those treated with DOAC (n=9947), 74% were administered SD (n=7238), 18% received LD per labels (n=1756) and 10% were inappropriately prescribed LD of DOACs (n=953). Both LD cohorts tended to have shorter duration of OAC therapy (figure) and higher discontinuation rates (per 100 person-years; LD per label: 42.97; LD not per label: 39.11) compared to the SD cohort (SD: 31.67). Patients who were untreated were associated with elevated bleeding risk factors such as renal disease and prior bleeding history; patients who received inappropriate LD were associated with age above 75, renal disease, GI conditions with PPI (proton pump inhibitor) concomitant treatments when compared to SD cohort. Conclusions: In our study, a considerable proportion of AF patients remained untreated/undertreated and were associated with bleeding risk factors, highlighting the unmet needs within this population. Exploring potential alternative treatment options with enhanced safety profiles could offer substantial benefits to patients in need.

Results of this study suggest that FXa inhibitors were associated with lung injury among patients with NVAF who were treated with OACs. Physicians should be vigilant in monitoring for any potential adverse lung outcomes associated with the use of these drugs.

Background and Purpose- Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods- In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score-matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results- The median follow-up period was 5.0 months (interquartile range, 2-7 months). The mean age was 68 years, and 63% were men in HDER group, and the mean age was 73 years, and 52% were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95% CI, 0.31-0.64; LDER: aHR, 0.57; 95% CI, 0.42-0.78), major bleeding (HDER: aHR, 0.40; 95% CI, 0.26-0.61; LDER: aHR, 0.61; 95% CI, 0.43-0.85), and mortality (HDER: aHR, 0.34; 95% CI, 0.22-0.53; LDER: aHR, 0.55; 95% CI, 0.41-0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels ( P for interaction=0.023). Conclusions- In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).