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1.
MT in anticoagulated patients: Direct oral anticoagulants versus vitamin K antagonists.
L'Allinec, V, Sibon, I, Mazighi, M, Labreuche, J, Kyheng, M, Boissier, E, Roy, M, Gory, B, Dargazanli, C, Desal, H, et al
Neurology. 2020;(8):e842-e850
Abstract
Mechanical thrombectomy (MT) is one of the main treatments for acute ischemic stroke (AIS) in patients on effective anticoagulation. The use of direct oral anticoagulants (DOA) has increased, given their efficacy and safety profile compared to vitamin K antagonists (VKA). We compared procedural and clinical outcomes of MT in patients on DOA and VKA treatment before stroke onset. We analyzed 2 groups from the Endovascular Treatment in Ischemic Stroke prospective registry: patients on DOA and patients on VKA treated by MT without thrombolysis. Generalized linear mixed models including center as random effect were used to compare angiographic (rates of reperfusion at end of procedure, number of passes >2, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to anticoagulation subgroups. Comparisons were adjusted for prespecified confounders (age, admission NIH Stroke Scale score) as well as for meaningful baseline between-group differences. Among 221 patients included, more DOA-treated patients (n = 115, 52%) achieved successful (modified Thrombolysis in Cerebral Infarction score [mTICI] 2b/3) or near complete (mTICI 2c/3) reperfusion at the procedure end than did VKA-treated patients, with an adjusted odds ratio (OR) for DOA vs VKA of 3.27 (95% confidence interval [CI], 1.40-7.65) and 2.00 (95% CI, 1.08-3.73), respectively. DOA-treated patients had a lower 90-day mortality risk with an adjusted OR of 0.47 (95% CI, 0.24-0.89) and a better excellent outcome OR of 2.40 (1.10-5.27). There was no significant between-group difference in hemorrhagic or procedural complications. The study highlights the benefits of DOA compared to VKA. Regarding mortality, excellent outcomes, and recanalization rate, DOA appears to provide a favorable setting for MT treatment in AIS.
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2.
Direct oral anticoagulants for extended treatment of venous thromboembolism: insights from the EINSTEIN CHOICE study.
Imberti, D, Pomero, F, Mastroiacovo, D
Blood transfusion = Trasfusione del sangue. 2020;(1):49-57
Abstract
The risk of recurrence of venous thromboembolism (VTE) persists after interruption of the initial anticoagulation therapy. New evidence shows that direct oral anticoagulants are effective for extended treatment of VTE and may reduce the risk of all-cause mortality. The optimal duration of anticoagulation after VTE is, however, controversial and complicated by the need for individualised assessment and balance between thrombosis and bleeding risks. Three direct oral anticoagulants (rivaroxaban, apixaban and dabigatran) have been studied for extended treatment of VTE. Dabigatran was shown to be safer than vitamin K antagonists and similarly effective for the prevention of recurrent VTE. Dabigatran, apixaban and rivaroxaban resulted in significant decreases in the rate of recurrent symptomatic VTE when compared to placebo, without a statistically significant difference in the risk of major bleeding. The latest guidelines of the American College of Chest Physicians suggest the use of low-dose aspirin to prevent VTE recurrence in patients who want to stop anticoagulation. In the randomised, double-blind, phase 3 EINSTEIN CHOICE trial, once-daily rivaroxaban at doses of 20 mg or 10 mg and 100 mg of aspirin were compared in VTE patients for whom there was clinical equipoise for extended anticoagulation. Either a treatment dose (20 mg) or a prophylactic dose (10 mg) of rivaroxaban significantly reduced the risk of VTE recurrence without a significant increase in bleeding risk compared with aspirin. The EINSTEIN CHOICE trial included patients with provoked or unprovoked VTE. Patients with VTE provoked by minor persistent or minor transient risk factors enrolled in this trial had not-negligible VTE recurrence rates. These new findings on extended therapy suggest the possibility of anticoagulation regimens at intensities tailored to the patients' risk profiles and VTE characteristics, with a shift of the risk-benefit balance in favour of extended treatment.
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3.
Bleeding in anticoagulated patients with atrial fibrillation: practical considerations.
Undas, A, Drabik, L, Potpara, T
Polish archives of internal medicine. 2020;(1):47-58
Abstract
Major bleeding (especially intracranial hemorrhage) is the most feared adverse event observed in patients with atrial fibrillation (AF) receiving oral anticoagulation. Clinical risk factor-based scores have modest ability to predict major or clinically relevant bleeds, and blood biomarkers are increasingly implemented to improve bleeding prognostication in patients with AF on life‑long anticoagulation. To improve the safety of anticoagulation in the era of non-vitamin K antagonist oral anticoagulants (NOACs, or direct oral anticoagulants [DOACs], including dabigatran, rivaroxaban, apixaban, and edoxaban), specific demographic, clinical, and laboratory variables should be considered. The current review summarizes practical challenges in the management of oral anticoagulation with emphasis on the risk assessment tools, elderly or underweight patients, cancer patients, impact of chronic kidney disease, liver cirrhosis, and thrombocytopenia in the context of bleeding risk in patients with AF.
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4.
Current practice of anticoagulant in the treatment of splanchnic vein thrombosis secondary to acute pancreatitis.
Norton, W, Lazaraviciute, G, Ramsay, G, Kreis, I, Ahmed, I, Bekheit, M
Hepatobiliary & pancreatic diseases international : HBPD INT. 2020;(2):116-121
Abstract
BACKGROUND Severe acute pancreatitis is a common diagnosis in emergency general surgery and can be a cause of significant morbidity and mortality. A consequence of severe acute pancreatitis is thrombus in the splanchnic veins. These thrombi can potentially lead to bowel ischemia or hepatic failure. However, another complication of severe acute pancreatitis is retroperitoneal bleeding. At this time, it is unclear if treating patients for splanchnic vein thrombosis in the context of severe acute pancreatitis is associated with any outcome benefit. A systematic review might clarify this question. DATA SOURCES A two-fold search strategy (one broad and one precise) looked at all published literature. The review was registered on PROSPERO (ID: CRD42018102705). MEDLINE, EMBASE, PubMed, Cochrane and Web of Science databases were searched and potentially relevant papers were reviewed independently by two researchers. Any disagreement was reviewed by a third independent researcher. Primary outcome was reestablishment of flow in the thrombosed vein versus bleeding complications. RESULTS Of 1462 papers assessed, a total of 16 papers were eligible for inclusion. There were no randomized controlled trials, 2 were case series, 5 retrospective single-center studies and 9 case reports. There were a total of 198 patients in these studies of whom 92 (46.5%) received anticoagulation therapy. The rates of recanalization of veins in the treated and non-treated groups was 14% and 11% and bleeding complications were 16% and 5%, respectively. However, the included studies were too heterogeneous to undertake a meta-analysis. CONCLUSIONS The systematic review highlights the lack evidence addressing this clinical question. Therefore a randomized controlled trial would be appropriate to undertake.
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5.
Severe Hemorrhage Associated With Oral Anticoagulants.
Lindhoff-Last, E, Herrmann, E, Lindau, S, Konstantinides, S, Grottke, O, Nowak-Goettl, U, Lucks, J, Zydek, B, Heymann, CV, Birschmann, I, et al
Deutsches Arzteblatt international. 2020;(18):312-319
Abstract
BACKGROUND Few data have been published to date on outcomes after the common clinical experience of severe hemorrhage in orally anticoagulated patients. METHODS A prospective, multicenter observational study was carried out to investigate outcomes and management in a series of consecutive patients who sustained a severe hemorrhage under treatment with vitamin K antagonists (VKA) or direct oral anticoagulant drugs (DOAC). The primary endpoint was in-hospital death up to and including day 30 after hospital admission. The secondary endpoints were the duration of bleeding, in-hospital death due to hemorrhage (as defined by the study physician examining the patient's records), the use of antagonists, the extent of supportive measures used to stop the hemorrhage, and an assessment of causality. Consecutive patients were recruited until a predefined number of patients was reached in both groups. RESULTS Among 193 patients with severe hemorrhage, 97 had been taking a VKA, and 96 had been taking a DOAC. 13.0 % (95% confidence interval [8.6; 18.5]; 25/193) of the overall group patients died in the first 30 days after hospital admission, including 17.5% ([10.6; 26.6]; 17/97) in the VKA group and 8.3% ([3.7; 15.8]; 8/96) in the DOAC group (p = 0.085). The median duration of bleeding was 19.8 hours in the VKA group and 27.8 hours in the DOAC group (p = 0.632). The in-hospital mortality due to hemorrhage was higher in the VKA group than in the DOAC group (15.5% [15/97] versus 4.2% [4/97]; p = 0.014). Only the use of prothrombin complex concentrates (PCCs) lowered the median duration of hemorrhage in the two patient groups. In 35% (68/193) of the patients, the hemorrhage was caused by an external influence, most commonly a fall. CONCLUSION The in-hospital mortality was higher among patients treated with VKA than among patients treated with DOAC, although the difference failed to reach statistical significance.
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Patient characteristics and stroke and bleeding events in nonvalvular atrial fibrillation patients treated with apixaban and vitamin K antagonists: a Spanish real-world study.
Ramagopalan, SV, Sicras-Mainar, A, Polanco-Sanchez, C, Carroll, R, de Bobadilla, JF
Journal of comparative effectiveness research. 2019;(14):1201-1212
Abstract
Aim: To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial fibrillation. Methods: An observational, retrospective study was performed using medical records of patients who initiated apixaban or acenocoumarol between 2015 and 2017. Propensity score matching was used to match patients; stroke, systemic thromboembolism, major and minor bleeding events were compared between the matched patients. Results: Patients who were prescribed apixaban had a lower rate of systemic embolism/stroke (hazard ratio [HR] = 0.54; 95% CI: 0.38-0.78; p = 0.001), minor bleeding (HR = 0.64; 95% CI: 0.52-0.79; p < 0.001) and major bleeding (HR = 0.51; 95% CI: 0.37-0.72; p < 0.001). Conclusion: Patients prescribed apixaban for the treatment of nonvalvular atrial fibrillation had lower rates of thromboembolic events and minor/major bleeding than patients on acenocoumarol.
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7.
A rapid evidence assessment of bleed-related healthcare resource utilization in publications reporting the use of direct oral anticoagulants for non-valvular atrial fibrillation.
Shah, BR, Scholtus, E, Rolland, C, Batscheider, A, Katz, JN, Nilsson, KR
Current medical research and opinion. 2019;(1):127-139
Abstract
Objective: Non-valvular atrial fibrillation (NVAF), a common cardiac arrhythmia, is associated with high morbidity and carries a substantial economic burden. Historically, vitamin K antagonists (VKAs; e.g. warfarin) have been used for therapy of NVAF, but recently several direct oral anticoagulants (DOACs) have been approved for prevention of stroke in patients with NVAF. This review summarizes the real-world evidence (RWE) for healthcare resource utilization (HRU) in patients receiving oral anticoagulants (VKAs and/or DOACs) for therapy of NVAF.Methods: A PRISMA-compliant literature search assessed Medline® and Embase® databases from 1 January 2011 to 4 May 2017, and the National Health Service Economic Evaluation Database from 1 January 2011 to 31 December 2015. Publications were included if they reported observational data from real-world use of one or more anticoagulant therapies. Outcomes of interest included hospitalizations, length of stay (LOS), mortality and costs.Results: Twenty-eight publications were included. Apixaban and dabigatran were associated with fewer bleed-related hospitalizations than warfarin. Bleed-related LOS were generally longer for warfarin than for DOACs. Bleed-related treatment costs were lower for patients receiving apixaban or receiving dabigatran than patients receiving rivaroxaban or receiving warfarin. Bleed-related mortality in patients receiving oral anticoagulation for treatment of NVAF were low across all DOACs and warfarin.Conclusions: The limited available evidence for HRU burden among patients receiving oral anticoagulation for NVAF suggests that DOACs (particularly apixaban and dabigatran) offer some degree of benefit in terms of HRU outcomes, compared with warfarin. Further work is required to understand HRU outcomes in patients receiving DOACs.
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8.
Direct-Acting Oral Anticoagulants in Critically Ill Patients.
Rali, P, Gangemi, A, Moores, A, Mohrien, K, Moores, L
Chest. 2019;(3):604-618
Abstract
The direct-acting oral anticoagulants (DOACs) have been increasingly used over vitamin K antagonists in recent years because they do not require monitoring and have an immediate anticoagulation effect. In general, DOACs have exhibited a better safety profile and noninferiority for prophylaxis and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation compared with vitamin K antagonists in the non-ICU population; whether this finding holds true in patients who are critically ill remains unknown. The current review addresses the role of DOACs in special ICU populations, use of these agents for VTE prophylaxis, perioperative management of DOACs, drug monitoring, and potential drug interactions of DOACs in critically ill patients. Adverse events and available reversal agents for DOACs are also discussed.
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9.
Efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a meta-analysis of randomized controlled trials.
Wang, KL, Lopes, RD, Patel, MR, Büller, HR, Tan, DS, Chiang, CE, Giugliano, RP
European heart journal. 2019;(19):1492-1500
Abstract
AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) require dose reductions according to patient or clinical factors for patients with atrial fibrillation (AF). In this meta-analysis, we aimed to assess outcomes with reduced-dose NOACs when given as pre-specified in pivotal trials. METHODS AND RESULTS Aggregated data abstracted from Phase III trials comparing NOACs with warfarin in patients with AF were assessed by treatment using risk ratios (RRs) and 95% confidence intervals (CIs) stratified by patient eligibility for NOAC dose reduction. Irrespective of treatments, annualized rates of stroke or systemic embolism and major bleeding were higher in patients eligible for reduced-dose NOACs than in those eligible for full-dose NOACs (2.70% vs. 1.60% and 4.35% vs. 2.87%, respectively). Effects of reduced-dose NOACs compared with warfarin in patients eligible for reduced-dose NOACs on stroke or systemic embolism [RR 0.84 (95% CI 0.69-1.03)] and on major bleeding [RR 0.70 (95% CI 0.50-0.97)] were consistent with those of full-dose NOACs relative to warfarin in those eligible for full-dose NOACs [RR 0.86 (95% CI 0.77-0.96) for stroke or systemic embolism and RR 0.87 (95% CI 0.70-1.08) for major bleeding; interaction P, 0.89 and 0.26, respectively]. In addition, NOACs were associated with reduced risks of haemorrhagic stroke, intracranial haemorrhage, fatal bleeding, and death regardless of patient eligibility for NOAC dose reduction (interaction P > 0.05 for each). CONCLUSIONS Patients eligible for reduced-dose NOACs were at elevated risk of thromboembolic and haemorrhagic complications when treated with anticoagulants. NOACs, when appropriately dose-adjusted, had an improved benefit-harm profile compared with warfarin. Our findings highlight the importance of prescribing reduced-dose NOACs for indicated patient populations.
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10.
Performance of the ABC Scores for Assessing the Risk of Stroke or Systemic Embolism and Bleeding in Patients With Atrial Fibrillation in ENGAGE AF-TIMI 48.
Berg, DD, Ruff, CT, Jarolim, P, Giugliano, RP, Nordio, F, Lanz, HJ, Mercuri, MF, Antman, EM, Braunwald, E, Morrow, DA
Circulation. 2019;(6):760-771
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Abstract
BACKGROUND The ABC (age, biomarker, clinical history)-stroke and ABC-bleeding risk scores incorporate clinical variables and cardiovascular biomarkers to estimate risk of stroke or systemic embolic events and bleeding, respectively, in patients with atrial fibrillation. These scores have been proposed for routine clinical use, but their performance in external cohorts remains uncertain. METHODS ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a multinational randomized trial of the oral factor Xa inhibitor edoxaban in patients with atrial fibrillation and a CHADS2 score ≥2. We performed a nested prospective biomarker study in 8705 patients, analyzing baseline high-sensitivity troponin T (hsTnT), NT-proBNP (N-terminal B-type natriuretic peptide), and growth differentiation factor-15 (GDF-15), as well as in serial samples after 12 months. The ABC-stroke (age, prior stroke/transient ischemic attack, hsTnT, NT-proBNP) and ABC-bleeding (age, prior bleeding, hemoglobin, hsTnT, and GDF-15) scores were tested. Hazard ratios were adjusted for estimated glomerular filtration rate and the components of the CHA2DS2-VASc and HAS-BLED scores, respectively. Discrimination and reclassification were compared with these established scores. RESULTS Median baseline hsTnT, NT-proBNP, and GDF-15 levels were 13.7 ng/L (25th-75th percentiles, 9.6-20.4 ng/L), 811 pg/mL (386-1436 pg/mL), and 1661 pg/mL (1179-2427 pg/mL), respectively. Elevated hsTnT, NT-proBNP, and GDF-15 were independently associated with higher rates of stroke or systemic embolic events, and elevated hsTnT and GDF-15 were independently associated with higher rates of major bleeding ( P<0.001 for each). The ABC-stroke and ABC-bleeding scores were well calibrated and yielded higher c indexes than the CHA2DS2-VASc score for stroke or systemic embolic events (0.67 [95% CI, 0.65-0.70] versus 0.59 [95% CI, 0.57-0.62]; P<0.001) and HAS-BLED score for major bleeding (0.69 [95% CI, 0.66-0.71] versus 0.62 [95% CI, 0.60-0.64]; P<0.001), respectively. The ABC-stroke and ABC-bleeding scores stratified patients within CHA2DS2-VASc and HAS-BLED risk categories ( P<0.001 for both). Patients with ABC-bleeding scores predicting a high 1-year risk of bleeding (>2%) derived greater benefit from treatment with edoxaban compared with warfarin. CONCLUSIONS The ABC-stroke and ABC-bleeding scores evaluated in this anticoagulated clinical trial cohort were well calibrated and outperformed the CHA2DS2-VASc and HAS-BLED scores, respectively. These scores may help identify patients most likely to derive a benefit from treatment with non-vitamin K antagonist oral anticoagulants. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT00781391.