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Predictors of post-traumatic complication of mild brain injury in anticoagulated patients: DOACs are safer than VKAs.
Cipriano, A, Park, N, Pecori, A, Bionda, A, Bardini, M, Frassi, F, Lami, V, Leoli, F, Manca, ML, Del Prato, S, et al
Internal and emergency medicine. 2021;(4):1061-1070
Abstract
Although mild traumatic brain injury (MTBI) in people on oral anticoagulant treatment (OAT) is a frequent challenge for Emergency Department (ED), strong guidelines recommendations are lacking. In the attempt to assess the safety profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs), we have recruited 473 patients with a MTBI on OAT (43.6% males; age 81.8 ± 8.7 years), admitted to the Pisa's University Hospital ED (Jan 2016-Oct 2018). All patients underwent a head CT scan with those with no sign of acute bleedings remaining under clinical observation for the ensuing 24 h. Fifty patients (10.6%, 95% CI: 8.1-13.7%) had immediate intracranial hemorrhage (ICH), with a prevalence of patient-important outcomes due to immediate ICH of 1.1% (95% CI 0.4-2.4%); 3 patients died (0.6%, 95% CI 0.2-1.8) and 2 required neurosurgical intervention. Immediate ICHs were more frequent in VKA-treated than in DOAC-treated patients (15.9 vs. 6.4%. RR 2.5. 95%CI 1.4-4.4. p < 0.05). Multivariate analysis identified that post-traumatic amnesia, evidence of trauma above clavicles, high blood glucose, high blood pressure (BP) at arrival, and low prothrombin activity were predictors of immediate ICH. The prevalence of delayed ICH was 1.0% (95%CI 0.4-2.5%) without differences between DOACs and VKAs. Despite ICH being a frequent complication of MTBI in patients on OAT, immediate and delayed patient-important outcomes are rare. DOACs have a better safety profile than VKAs. Simple clinical parameters such as blood pressure at arrival or blood glucose might provide useful predictors of immediate ICH.Trial registration number: 11924_CIPRIANO. Local ethics committee approval number 33096.
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Regional citrate anti-coagulation dose titration: impact on dose of continuous renal replacement therapy.
Ng, CJH, Poh, CB, Koduri, S, Roy, DM, Siau, C, Lim, NL, Chionh, CY
Clinical and experimental nephrology. 2021;(9):963-969
Abstract
BACKGROUND Regional citrate anti-coagulation (RCA) is the recommended anti-coagulation for continuous renal replacement therapy (CRRT). Citrated replacement fluids provide convenience but may compromise effluent delivery when adjusted to maintain circuit ionised calcium levels (circuit-iCa). This study aims to evaluate the effect of RCA titration on the delivered CRRT effluent dose. METHODS This prospective observational study evaluated patients on RCA-CRRT in continuous veno-venous hemodiafiltration mode. Citrated replacement fluid was titrated to target circuit-iCa 0.26-0.40 mmol/L. Patients were then stratified into 'reduced-dose' who required citrate down-titration and 'stable-dose' who did not. RESULTS Data from 200 RCA-CRRT sessions were collected. The reduced-dose RCA group (n = 114) had higher median initial citrate dose (3.00 vs 2.50; P < 0.001) but lower time-averaged dose (2.49 vs 2.60; P < 0.001). In addition, median prescribed effluent dose was 33.3 mL/kg/h (28.6-39.2) but median delivered effluent dose was significantly lower at 29.9 mL/kg/h (25.4-36.9; P < 0.001). Mortality was higher in the reduced-dose RCA group (39.5% vs 25.6%; P = 0.022) and in patients with delivered-to-prescribed effluent dose ratio of < 0.9 vs ≥ 0.9 (51.3% vs 29.2%; P = 0.014). CONCLUSION RCA titration can significantly impact delivered CRRT effluent dose. Measures should be taken to address the CRRT dose deficit and prevent poor outcomes due to inadequate dialysis.
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3.
Bleeding risks associated with anticoagulant therapies after percutaneous coronary intervention in Japanese patients with ischemic heart disease complicated by atrial fibrillation: A comparative study.
Nakamura, M, Yamashita, T, Hayakawa, A, Matsumoto, T, Takita, A, Hasegawa, C, Uchino, K, Sekine, T, Iizuka, T, Tanabe, H, et al
Journal of cardiology. 2021;(2):186-194
Abstract
BACKGROUND Current guidelines recommend early termination of triple therapy and the use of direct oral anticoagulants (DOAC) for non-valvular atrial fibrillation (NVAF) patients who undergo percutaneous coronary intervention (PCI), due to safety concerns. However, to date, real-world medication usage and safety outcomes (specifically bleeding) in NVAF patients with stent implantation have not been well assessed. METHODS This was a retrospective, observational, medical database cohort study in Japanese ischemic heart disease (IHD) patients with NVAF who underwent PCI between 2012 and 2017. The primary outcome was clinically relevant bleeding; secondary outcomes included individual bleeding events. A multivariate analysis was conducted to identify risk factors affecting the occurrence of clinically relevant bleeding events. RESULTS The analysis population comprised 5695 patients [3530 received DOACs and 2165 received vitamin K antagonists (VKAs)]. The incidence of primary outcome events (clinically relevant bleeding/100 patient-years) was 6.05 in the DOAC group and 8.42 in the VKA group, resulting in a nonsignificant 21% lower risk in the DOAC group. The DOAC group also had a nonsignificant 24%, 24%, and 34% lower risk of bleeding requiring transfusion, intracranial bleeding, and lower gastrointestinal bleeding, respectively, compared with the VKA group. A multivariate analysis of the primary outcome showed a significantly higher risk of bleeding among older patients and those with lower body weight and abnormal renal function. CONCLUSIONS In this retrospective real-world evaluation of IHD patients with NVAF and PCI, DOAC-treated patients had a lower risk of developing clinically relevant bleeding compared with the VKA group.
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Characteristics of patients receiving extended treatment after incident venous thromboembolism.
Albertsen, IE, Jensen, M, Abdelgawwad, K, Søgaard, M, Larsen, TB, Nielsen, PB
Basic & clinical pharmacology & toxicology. 2021;(4):332-342
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Abstract
Given high recurrence risk after venous thromboembolism (VTE), guidelines recommend extended dose rivaroxaban (10 mg OD) or apixaban (2.5 mg BID) to be considered after 6 months of initial treatment. This study aimed to provide insight into clinical practice regarding the use of extended preventive treatment and to describe duration of the initial treatment. Linkage of nationwide health registers identified all in- and outpatients with VTE from April 2017 through 2018. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated adjusting for other VTE-related factors. The study included 6030 patients with VTE. Among rivaroxaban users, 2.2% (n = 113) received the extended 10-mg dose after mean 9.4 (SD 3.1) months of standard treatment. For apixaban, 4.7% (n = 40) received extended 2.5-mg dose after mean 8.0 months (SD 3.9). After adjustments, incident pulmonary embolism (HR 1.81 95% CI 1.12;2.91) and trauma/fracture (HR 1.42 95% CI 0.46;4.43) were associated with switching to extended dose, whereas patients with unprovoked VTE were less likely to receive the extended dose (HR 0.68 95% CI 0.30;1.55). Less than 3% of patients with incident VTE received extended treatment after initial standard treatment. Even though international guidelines suggest that the risk-benefit balance is in favour of extended VTE treatment, this was yet to be translated into clinical practice as of 2018. Studies using contemporary data are warranted to investigate routine clinical practice of extended treatment for VTE recurrence.
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Demographic, clinical, and functional determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation.
Mostaza, JM, Suarez, C, Cepeda, JM, Manzano, L, Sánchez, D, ,
BMC cardiovascular disorders. 2021;(1):384
Abstract
BACKGROUND This study assessed the sociodemographic, functional, and clinical determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation (NVAF) attended in the internal medicine setting. METHODS A multicenter, cross-sectional study was conducted in NVAF patients who attended internal medicine departments for either a routine visit (outpatients) or hospitalization (inpatients). RESULTS A total of 961 patients were evaluated. Their antithrombotic management included: no treatment (4.7%), vitamin K antagonists (VKAs) (59.6%), direct oral anticoagulants (DOACs) (21.6%), antiplatelets (6.6%), and antiplatelets plus anticoagulants (7.5%). Permanent NVAF and congestive heart failure were associated with preferential use of oral anticoagulation over antiplatelets, while intermediate-to high-mortality risk according to the PROFUND index was associated with a higher likelihood of using antiplatelet therapy instead of oral anticoagulation. Longer disease duration and institutionalization were identified as determinants of VKA use over DOACs. Female gender, higher education, and having suffered a stroke determined a preferential use of DOACs. CONCLUSIONS This real-world study showed that most elderly NVAF patients received oral anticoagulation, mainly VKAs, while DOACs remained underused. Antiplatelets were still offered to a proportion of patients. Longer duration of NVAF and institutionalization were identified as determinants of VKA use over DOACs. A poor prognosis according to the PROFUND index was identified as a factor preventing the use of oral anticoagulation.
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Long-Term Risk of Major Adverse Cardiac Events in Atrial Fibrillation Patients on Direct Oral Anticoagulants.
Pastori, D, Menichelli, D, Del Sole, F, Pignatelli, P, Violi, F, ,
Mayo Clinic proceedings. 2021;(3):658-665
Abstract
OBJECTIVE To determine the association between direct oral anticoagulant (DOAC) use and risk of major adverse cardiac events (MACEs) in patients with atrial fibrillation (AF). PATIENTS AND METHODS This study is a single-center prospective observational cohort study including 2366 outpatients with non-valvular AF on treatment with DOACs or vitamin K antagonists (VKAs) from February 2008 for patients on VKA and September 2013 for patients on novel oral anticoagulants. The primary endpoint was the incidence of MACE including fatal and non-fatal myocardial infarction (MI), cardiac revascularization, and cardiovascular death. RESULTS The mean age was 75.1±9.0 years; 44.7% were women. During a mean follow-up of 33.3±21.9 months (6567 patients/years) 133 MACEs occurred (2.03%/year): 79 MI/cardiac revascularization and 54 cardiovascular deaths. Of these, 101 were on VKAs (2.42%/year) and 32 on DOACs (1.34%/year; log-rank test P=.040). This difference was evident also considering MI alone (1.53%/year and 0.63%/year in the VKA and DOAC group, respectively, log-rank test P=.009). At multivariable Cox proportional hazard regression analysis, use of DOACs was associated with a lower risk of MACE (hazard ratio, 0.636; 95% CI, 0.417 to 0.970; P=.036) and MI (hazard ratio, 0.497; 95% CI, 0.276 to 0.896; p=.020). Sensitivity analysis showed that this association was consistent in younger patients (<75 years), in patients with anemia, and in those without chronic obstructive pulmonary disease and heart failure. We also found that both dabigatran and apixaban/rivaroxaban were associated with a lower rate of MACE, with similar efficacy between full and low doses. CONCLUSION DOACs are associated with a lower risk of MACE in patients with AF independently from dosage.
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Comparison of Anticoagulation Quality between Acenocoumarol and Warfarin in Patients with Mechanical Prosthetic Heart Valves: Insights from the Nationwide PLECTRUM Study.
Menichelli, D, Poli, D, Antonucci, E, Cammisotto, V, Testa, S, Pignatelli, P, Palareti, G, Pastori, D, The Italian Federation Of Anticoagulation Clinics Fcsa,
Molecules (Basel, Switzerland). 2021;(5)
Abstract
Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones (p < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.
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[Mortality in patients with intracerebral haemorrhage associated with oral anticoagulation. Efficacy of a reversal protocol and clinical follow-up (ICH-OAC project)].
Amores-Valenciano, P, Ruiz Escribano-Taravilla, E, Romero-Sánchez, CM, Prado-Mira, A, García-Gil, E, Espejo-López, AB, Collado-Jiménez, RM, Molina-Nuevo, JD, Marín-Sánchez, A, Hernández-Fernández, F
Revista de neurologia. 2021;(5):165-173
Abstract
INTRODUCTION Spontaneous intracerebral haemorrhage associated with oral anticoagulants (ICH-OAC) has a high mortality rate. The emergence of new anticoagulant drugs and reversal protocols increases interest in this entity. OBJECTIVES The main objective is to determine the mortality rate in patients with ICH-OAC (early, in-hospital, global) in our health area and to analyse the main variables related to it. The secondary objective is to determine the efficacy of anticoagulation reversal therapies (ART) as reflected by radiological expansion of the haematoma and the functional prognosis. PATIENTS AND METHODS A prospective observational study that introduced a protocol aimed at the management of patients with ICH-OAC. It included general measures and neuromonitoring, individualised administration of ART, cranial tomography and a six-month follow-up. Data on the drugs prescribed in the area during this period, mortality and functional prognosis were collected. A bivariate and logistic regression study was designed to investigate mortality-related variables. RESULTS Forty-nine patients were included over three years; of these, 71.4% received ART. Mortality was 16.3% (first 24 hours), 53.1% (admission) and 61.2% (180 days). Lower survival was observed among patients with higher baseline scores on the National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001), creatinine value (p = 0.02), International Normalised Index (p = 0.048), bleeding volume (p = 0.008), hydrocephalus (p = 0.015) and acenocoumarol intake (p = 0.030). Patients who did not receive ART had a greater rate of early mortality (p = 0.003). The only variable independently related to overall mortality was the baseline NIHSS score (odds ratio = 1.282; 95% confidence interval: 1.023-1.608; p = 0.031). CONCLUSIONS ICH-OAC has a high mortality rate, related to the use of acenocoumarol and regardless of the initial clinical situation. A lower rate of early mortality was found among patients who received ART.
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Body Mass Index and Clinical Outcomes in Asian Patients With Atrial Fibrillation Receiving Oral Anticoagulation.
Lee, SR, Choi, EK, Jung, JH, Park, SH, Han, KD, Oh, S, Lip, GYH
Stroke. 2021;(2):521-530
Abstract
BACKGROUND AND PURPOSE The influence of body mass index (BMI) on clinical outcomes in patients with atrial fibrillation remains controversial, especially among Asians. We aimed to evaluate the association between BMI and clinical outcomes in Asian patients with atrial fibrillation receiving oral anticoagulants. METHODS Using the Korean National Health Insurance database between January 2015 and December 2017, we identified oral anticoagulant new users among patients with nonvalvular atrial fibrillation who had BMI information. We analyzed ischemic stroke, intracranial hemorrhage, hospitalization for gastrointestinal bleeding, major bleeding, all-cause death, and the composite clinical outcome according to BMI categories. RESULTS A total of 43 173 patients were included across BMI categories (kg/m2): underweight (<18.5) in 3%, normal (18.5 to <23) in 28%, overweight (23 to <25) in 24%, obese I (25 to <30) in 39%, and obese II (≥30) in 6%. Higher BMI (per 5 kg/m2 increase) was significantly associated with lower risks of ischemic stroke (hazard ratio [HR], 0.891 [95% CI, 0.801-0.992]), hospitalization for gastrointestinal bleeding (HR, 0.785 [95% CI, 0.658-0.937]), major bleeding (HR, 0.794 [95% CI, 0.686-0.919]), all-cause death (HR, 0.658 [95% CI, 0.605-0.716]), and the composite clinical outcome (HR, 0.751 [95% CI, 0.706-0.799]), except for intracranial hemorrhage (HR, 0.815 [95% CI, 0.627-1.061]). The underweight group was associated with an increased risk of composite clinical outcome (HR, 1.398 [95% CI, 1.170-1.671]), mainly driven by an increased risk of all-cause death. The effects of non-vitamin K antagonist oral anticoagulant versus warfarin on clinical outcomes were similar across BMI groups. CONCLUSIONS Higher BMI was independently associated with a lower risk of ischemic stroke, major bleeding, and better survival. Underweight patients had a higher risk of all-cause death and composite clinical outcome. The optimal BMI for patients with atrial fibrillation should be defined and managed according to an integrated care pathway.
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Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Prior Gastrointestinal Bleeding.
Kwon, S, Lee, SR, Choi, EK, Lee, E, Jung, JH, Han, KD, Cha, MJ, Oh, S, Lip, GYH
Stroke. 2021;(2):511-520
Abstract
BACKGROUND AND PURPOSE Limited data support the benefits of non-vitamin K oral anticoagulants (NOACs) among atrial fibrillation patients with prior gastrointestinal bleeding (GIB). We aimed to evaluate the effectiveness and safety of NOACs compared with those of warfarin among atrial fibrillation patients with prior GIB. METHODS Oral anticoagulant-naive individuals with atrial fibrillation and prior GIB between January 2010 and April 2018 were identified from the Korean claims database. NOAC users were compared with warfarin users by balancing covariates using the inverse probability of treatment weighting method. The primary outcomes were ischemic stroke, major bleeding, and the composite outcome (combined ischemic stroke and major bleeding). Fatal events from each outcome were evaluated as secondary outcomes. RESULTS A total of 42 048 patients were included (24 781 in the NOAC group and 17 267 in the warfarin group). The mean time from prior GIB to the initiation of oral anticoagulant was 3.1±2.6 years. After inverse probability of treatment weighting, baseline characteristics were balanced between the two groups (mean age, 72 years; men, 56.8%; and mean CHA2DS2-VASc score, 3.7). Lower risks of ischemic stroke, major bleeding, and the composite outcome were associated with NOAC use than with warfarin use (weighted hazard ratio, 0.608 [95% CI, 0.543-0.680]; hazard ratio, 0.731 [95% CI, 0.642-0.832]; and hazard ratio, 0.661 [95% CI, 0.606-0.721], respectively). For all secondary outcomes, NOACs showed greater risk reductions compared with warfarin. CONCLUSIONS NOACs were associated with lower risks of ischemic stroke and major bleeding than warfarin among atrial fibrillation patients with prior GIB.