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1.
J Cardiovasc Pharmacol Ther ; 27: 10742484221128124, 2022.
Статья в английский | MEDLINE | ID: covidwho-2053690

Реферат

BACKGROUND: Because of logistic challenges associated with the COVID-19 pandemic, direct oral anticoagulants (DOAC) were favored over warfarin in patients presenting postoperative atrial fibrillation (AF) after cardiac surgery in our institution. Considering the limited evidence supporting the use of DOAC in this context, we sought to evaluate the safety and efficacy of this practice change. METHODS: A retrospective study was performed with patients from the Quebec City metropolitan area who were hospitalized at the Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval following cardiac surgery and who required oral anticoagulant (OAC) for postoperative AF. The primary objective was to compare the pre- and peri-COVID-19 period for OAC prescribing patterns and the incidence of thrombotic and bleeding events at 3 months post-surgery. The secondary objective was to compare DOAC to warfarin in terms of thrombotic events and bleeding events. RESULTS: A total of 233 patients were included, 142 from the pre-COVID-19 and 91 from the peri-COVID-19 period, respectively. Both groups had equivalent proportions of preoperative AF (48%) and new-onset postoperative AF (52%). The proportion of patients treated with a DOAC increased from 13% pre-COVID-19 to 82% peri-COVID-19. This change in practice was not associated with a significant difference in the incidence of thrombotic or bleeding events 3 months postoperatively. However, compared to DOAC, warfarin was associated with a higher incidence of major bleeding. Only 1 thrombotic event was reported with warfarin, and none were reported with DOAC. CONCLUSION: This study suggests that DOAC are an effective and safe alternative to warfarin to treat postoperative AF after cardiac surgery and that this practice can be safely maintained.


Тема - темы
Atrial Fibrillation , COVID-19 , Cardiac Surgical Procedures , Stroke , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Cardiac Surgical Procedures/adverse effects , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Pandemics , Retrospective Studies , Stroke/epidemiology , Warfarin/adverse effects
2.
Indian J Med Res ; 155(5&6): 526-537, 2022.
Статья в английский | MEDLINE | ID: covidwho-2040110

Реферат

Background & objectives: The high mortality associated with the thrombotic events in hospitalized COVID-19 patients resulted in the usage of anticoagulants in varying doses. Whether high-dose anticoagulants have led to better outcomes or higher incidence of clinically significant bleeding events is debatable. Thus, this study was conducted to find the incidence of clinically significant bleeding events in moderate-to-severe COVID-19 ARDS (acute respiratory distress syndrome) patients on therapeutic anticoagulation and their outcomes. Methods: In this retrospective, single-centre study of 155 critically ill COVID-19 patients, the incidence of clinically significant bleeding was observed. Multivariate regression models were used to evaluate the association between anticoagulant regimen, coagulation and inflammatory markers with the incidence of bleeding and thrombotic events. Results: The incidence of clinically relevant non-major bleeding was 33.54 per cent (26.17-41.46%) and major bleeding was 9.03 per cent (5.02-14.69%). The anticoagulation intensity at baseline had a high odds of major bleeding when enoxaparin and dual antiplatelet therapy were used together [adjusted odds ratio OR of 434.09 (3.81-49502.95), P<0.05]. At admission, bleeders had a poorer PaO2/FiO2 ratio with more patients on invasive ventilation. At the time of bleeding, the bleeders had a higher D-dimer, ferritin, C-reactive protein and procalcitonin compared to non-bleeders. The subhazard ratio for death in bleeders was 3.35 (95% confidence interval, 1.97-5.65; P<0.001). Interpretation & conclusions: The incidence of bleeding in critically ill COVID-19 patients on therapeutic anticoagulation may increase with the severity of the disease as well as with concurrent use of dual antiplatelets. Major bleeding may also contribute to higher mortality.


Тема - темы
COVID-19 , Respiratory Distress Syndrome , Thrombosis , Humans , Anticoagulants , COVID-19/complications , COVID-19/drug therapy , Retrospective Studies , Critical Illness , Incidence , Hemorrhage/chemically induced , Hemorrhage/epidemiology
3.
Circulation ; 146(18): 1344-1356, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2020592

Реферат

BACKGROUND: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain. METHODS: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2×2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit-level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (≈50% planned recruitment) because of waning intensive care unit-level COVID-19 rates. RESULTS: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08-3.55]; P=0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32-0.99]; P=0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose (P=0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P=0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56-1.48]; P=0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy. CONCLUSIONS: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04409834.


Тема - темы
COVID-19 , Thrombosis , Venous Thrombosis , Humans , Critical Illness , Thrombosis/drug therapy , Clopidogrel/therapeutic use , Hemorrhage/chemically induced , Anticoagulants/adverse effects , Venous Thrombosis/drug therapy , Venous Thrombosis/epidemiology , Venous Thrombosis/prevention & control , Platelet Aggregation Inhibitors/adverse effects , Treatment Outcome
4.
Thromb Res ; 219: 40-48, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2008145

Реферат

BACKGROUND: Thromboembolic events are common complications of COVID-19. Clinical study results on safety and efficacy of anticoagulation in COVID-19 are controversial. MATERIAL AND METHODS: This report updates our systematic review and random-effects meta-analysis on randomized controlled trials (RCTs) comparing standard prophylactic anticoagulation and intermediate or therapeutic anticoagulation in COVID-19 patients. We searched eligible studies for the update up to 4 February 2022 by weekly monitoring of RCTs in the Cochrane COVID-19 Study Register. Certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: For this update we included five new trials; a total of 13 RCTs with 7364 patients. Certainty of evidence was very low to low. We are uncertain whether low-dose prophylactic anticoagulation is favoured over placebo or no anticoagulation in the outpatient- or post-discharge-setting. In hospitalized patients with moderate and severe COVID-19, intermediate-dose anticoagulation may have little or no effect on thrombotic events or death (RR 1.03, 95 % CI 0.86-1.24), but may increase severe bleeding non-significantly (RR 1.48, 95 % CI 0.53-4.15). Therapeutic-dose anticoagulation may decrease thrombotic events or deaths in hospitalized patients with moderate COVID-19 (RR 0.64, 95 % CI 0.38-1.07; fixed-effect model RR 0.72, 95 % CI 0.57-0.91), but may have little or no effect in patients with severe disease (RR 0.98, 95 % CI 0.86-1.12). With therapeutic-dose anticoagulation, the risk of major bleeding may increase regardless of COVID-19 severity (RR 1.78, 95 % CI 1.15-2.74). CONCLUSIONS: Hospitalized, moderately ill COVID-19 patients may benefit from therapeutic-dose anticoagulation, while critically ill patients may not. Risk of major bleeding must be considered.


Тема - темы
COVID-19 , Thromboembolism , Thrombosis , Anticoagulants/adverse effects , Blood Coagulation , COVID-19/complications , COVID-19/drug therapy , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Humans , Thromboembolism/drug therapy , Thromboembolism/etiology , Thromboembolism/prevention & control , Thrombosis/chemically induced , Thrombosis/etiology
5.
Curr Med Res Opin ; 38(11): 1891-1896, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-1996945

Реферат

INTRODUCTION: This study evaluated the risk of hospitalization among nonvalvular atrial fibrillation (NVAF) patients with an outpatient COVID-19 diagnosis who discontinued vs continued apixaban treatment. METHODS: Adult patients with NVAF with an apixaban prescription prior to an outpatient COVID-19 diagnosis were identified from Optum Clinformatics claims database (1 April 2020-31 March 2021). Continuers were those who continued apixaban as of the index date (date of initial outpatient COVID-19 diagnosis) and discontinuers were those who had the last day of apixaban supply on or before index. Patients were followed from COVID-19 diagnosis to change of continuation/discontinuation status, switch, death, end of continuous coverage or study end, whichever occurred first. Inverse probability treatment weighting (IPTW) was performed to balance cohorts. Cox proportional hazard models were used to compare the risk of all-cause hospitalization and hospitalization for ischemic stroke (IS), venous thromboembolism (VTE), myocardial infarction (MI), bleeding and mortality. RESULTS: A total of 7869 apixaban patients with COVID-19 were included: 6676 continuers (84.8%) and 1193 discontinuers (15.2%). Compared with continuers, discontinuers had a higher risk of all-cause hospitalization (hazard ratio [HR]: 1.23; 95% confidence interval [CI]: 1.08-1.40), IS (HR: 2.00; 95% CI: 1.03-3.87), VTE (HR: 2.37; 95% CI: 1.06-5.27) and mortality (HR: 2.28; 95% CI: 1.85-2.80). There were no significant differences in the risk of MI (HR: 1.01; 95% CI: 0.54-1.90) or bleeding-related hospitalization (HR: 1.13; 95% CI: 0.73-1.76). CONCLUSION: NVAF patients with COVID-19 who discontinued apixaban had a higher risk of hospitalization and thrombotic events vs those who continued apixaban, with no significant difference in bleeding-related hospitalization.


Тема - темы
Atrial Fibrillation , COVID-19 , Stroke , Venous Thromboembolism , Adult , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Anticoagulants , COVID-19 Testing , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , Retrospective Studies , Pyridones/adverse effects , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Hemorrhage/complications , Hospitalization
6.
Ann Cardiol Angeiol (Paris) ; 71(5): 245-251, 2022 Nov.
Статья в французский | MEDLINE | ID: covidwho-1982546

Реферат

AIM: Outpatient treatment (OT) of patients with low-risk pulmonary embolisms (PE) is recommended. A multidisciplinary OT program including the general practitioner (GP) has been implemented at Versailles hospital in 2019. The objectives of the study were to assess the feasibility, safety and acceptability of the program. MATERIAL AND METHODS: The feasibility of, and the inclusion criteria for OT were defined from a retrospective cohort study of PE patients carried out in 2018. In the prospective study, consecutive patients consulting in the emergency department between 2019 and 2021 with confirmed PE were eligible for OT if they had sPESI and HESTIA scores equal to 0, normal troponin and NT-pro-BNP levels, and no right ventricular dilation on imaging. PEs associated with COVID were excluded. The OT program included 4 appointments within 3 months, including 2 with the GP. Events (death, recurrence of PE or venous thromboembolism, bleeding, rehospitalisation) were collected at 3-month follow-up. RESULTS: In the retrospective study, 19% of the 138 PE patients seen in the emergency department were eligible for OT. No complication occurred at Day 90. In the prospective study, 313 consecutive patients with confirmed PE in the emergency department were included, 66 (21%) were eligible for OT. Overall, 43 patients (14%) received OT (39 eligible) and 27 patients eligible for OT were hospitalised (92% because of pulmonary infarction). At 3-month follow-up, there were no death, no recurrence of thromboembolism, and one patient has been early hospitalised for COVID; 3 female patients treated with rivaroxaban had minor bleeding (heavy menstrual bleeding). The satisfaction rate of general practitioner was 95%. CONCLUSIONS: This study confirms the feasibility and safety of our OT program for low-risk EP patients, centered on the general practitioner. It reduces the time spent in the emergency department, reduces hospitalisations and strengthens the city-hospital link for care.


Тема - темы
COVID-19 , General Practitioners , Pulmonary Embolism , Humans , Female , Retrospective Studies , Prospective Studies , Outpatients , Pulmonary Embolism/therapy , Hemorrhage/chemically induced , Anticoagulants/adverse effects
8.
PLoS One ; 17(8): e0270195, 2022.
Статья в английский | MEDLINE | ID: covidwho-1974308

Реферат

INTRODUCTION: There are no clear data about the incidence and the prophylactic strategies of arterial and venous thromboembolic events (TE) in COVID-19 ambulatory patients. Thus, we conducted this study to analyze thromboembolic complications in this setting and to assess thromboprophylaxis management and outcomes in the real life. PATIENTS AND METHODS: This is an observational study including Covid-19 ambulatory patients. We assessed incidence of venous and arterial TE events as well as thromboprophylaxis outcomes and hemorrhagic complications. We defined high risk thrombo-embolic factor according to the Belgian guidelines which are the only guidelines that described thromboprophylaxis in COVID-19 ambulatory patients. RESULTS: We included 2089 patients with a mean age of 43±16 years. The incidence of 30 days venous and arterial TE complications in our cohort was 1%. Venous thromboembolic complications occurred in 0.8% and arterial thromboembolic complications occurred in 0.3%.We noted at least one high-risk TE factor in 18.5% of patients but thromboprophylaxis was prescribed in 22.5% of the cases, LMWH in 18.1%, and Rivaroxaban in 3.7%. Hemorrhagic events occurred in eight patients (0.3%): five patients showed minor hemorrhagic events and three patients showed major ones (0.14%). CONCLUSIONS: Our study showed that the incidence of thromboembolic complications is very low in COVID-19 ambulatory patients. Paradoxically, there is an over prescription of thrombo-prophylaxis in this population.


Тема - темы
COVID-19 , Venous Thromboembolism , Adult , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Hemorrhage/chemically induced , Hemorrhage/complications , Hemorrhage/epidemiology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Incidence , Middle Aged , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
9.
Clin Appl Thromb Hemost ; 28: 10760296221116350, 2022.
Статья в английский | MEDLINE | ID: covidwho-1974064

Реферат

Objective: To compare Anti-Xa directed thromboprophylaxis using low molecular weight heparin (LMWH) (anti-Xa peak goal 0.2-0.5 IU/mL) to alternative anticoagulation strategies in critically ill COVID-19 patients. Methods: This was a retrospective, multicenter, single health-system study. Primary outcomes were thromboembolic events and clinically important bleeding events. Secondary outcomes included dosing comparisons between LMWH cohorts. Main Results: A total of 695 patients were included. No differences were found in the incidence of thrombotic events with any of the dosing strategies. The incidence of major bleeding was significantly higher in the standard dose thromboprophylaxis, intermediate dose subcutaneous heparin (SQH), and therapeutic anticoagulation cohorts. Forty-nine percent of patients within the anti-Xa directed group had their first anti-Xa peak at goal, while 43% were above goal. Patients who had levels above goal had dose modifications made, therefore anti-Xa directed LMWH resulted in significantly lower total daily doses compared to intermediate dose LMWH. Conclusions: Anti-Xa directed LMWH dosing provided comparable thromboprophylaxis with lower total daily doses of LMWH in critically ill COVID-19 patients. Further randomized controlled trials are needed to confirm our findings.


Тема - темы
COVID-19 , Venous Thromboembolism , Anticoagulants , Critical Illness , Hemorrhage/chemically induced , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Retrospective Studies , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
10.
J Thromb Thrombolysis ; 54(3): 420-430, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-1971785

Реферат

Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality among patients. Although international guidelines agree on the need for anticoagulation, it is unclear whether full-dose heparin anticoagulation confers additional benefits over prophylactic-dose anticoagulation. This systematic review and meta-analysis aimed to investigate the efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients. We searched Pubmed/Medline, EMBASE, Clinicaltrials.gov, medRxiv.org and Cochrane Central Register of clinical trials dated up to April 2022. Randomized controlled trials (RCTs) comparing full-dose heparin anticoagulation to prophylactic-dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients were included in our pooled analysis. The primary endpoint was the rate of major thrombotic events and the co-primary endpoint was the rate of major bleeding events. We identified 4 studies, all of them multicenter, randomizing 2926 patients. Major thrombotic events were 23/1524 (1.5%) in full-dose heparin anticoagulation versus 57/1402 (4.0%) in prophylactic-dose [relative risk (RR) 0.39; 95% confidence interval (CI) 0.25-0.62; p˂0.01; I2 = 0%]. Clinical relevant bleeding events occurred in 1.7% (26/1524) among patients treated with heparin full anticoagulation dose compared to 1.1% (15/1403) in prophylactic-dose group (RR 1.60; 95% CI 0.85-3.03; p = 0.15; I2 = 20%). Mortality was 6.6% (101/1524) versus 8.6% (121/1402) (RR 0.63; 95% CI 0.33-1.19; p = 0.15). In this meta-analysis of high quality multicenter randomized trials, full-dose anticoagulation with heparin was associated with lower rate of major thrombotic events without differences in bleeding risk and mortality in hospitalized non critically ill COVID-19 patients.Study registration PROSPERO, review no. CRD42022301874.


Тема - темы
COVID-19 , Thrombosis , Anticoagulants/adverse effects , COVID-19/drug therapy , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Thrombosis/prevention & control
11.
ASAIO J ; 68(7): 920-924, 2022 07 01.
Статья в английский | MEDLINE | ID: covidwho-1967929

Реферат

Extracorporeal membrane oxygenation (ECMO) contributes to coagulopathy, necessitating systemic anticoagulation to prevent thrombosis. Traditionally, unfractionated heparin (UFH) has been the anticoagulant of choice, however, due to many inadequacies new evidence suggests benefit with the use of direct thrombin inhibitors. This retrospective cohort sought to evaluate the safety and efficacy of bivalirudin compared to UFH in ECMO patients. Primary endpoints included incidence of bleeding and thrombosis. Percent time in therapeutic range (TR), time to achieve TR and number of dose titrations required to maintain TR were calculated to assess efficacy of institutional protocols. Overall incidence of thrombosis was low, with one event in the bivalirudin group and no events in the UFH group. No difference was found in rates of bleeding between groups (6% vs . 10%, P = 0.44). Bivalirudin yielded higher percent time in TR (86% vs. 33%, P < 0.001), faster time to TR (2 vs . 18 hr, P < 0.001) and required fewer dose adjustments to maintain TR (2 vs . 11, P < 0.001) compared to UFH. These results suggest bivalirudin and UFH are associated with similar rates of bleeding and thrombosis in patients requiring ECMO support. Our results demonstrate the favorable pharmacokinetic profile of bivalirudin, and its ability to consistently maintain TR when compared to UFH.


Тема - темы
Extracorporeal Membrane Oxygenation , Thrombosis , Adult , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Antithrombins/therapeutic use , Extracorporeal Membrane Oxygenation/adverse effects , Fibrinolytic Agents/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/complications , Hemorrhage/prevention & control , Heparin/adverse effects , Heparin/therapeutic use , Hirudin Therapy , Hirudins/adverse effects , Humans , Peptide Fragments/adverse effects , Peptide Fragments/therapeutic use , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Retrospective Studies , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control , Treatment Outcome
12.
BMC Emerg Med ; 22(1): 107, 2022 06 14.
Статья в английский | MEDLINE | ID: covidwho-1951062

Реферат

BACKGROUND: The optimal prophylactic dose of heparin in patients with coronavirus-associated disease 2019 (COVID-19) in the emergency department (ED) is debated. This study aimed to analyze different thromboprophylaxis approaches in unvaccinated COVID-19 patients admitted to ED without initial venous thromboembolism. METHODS: Retrospectively, the effect of intermediate/high versus low dose heparin treatment was evaluated from December 2020 to July 2021 in a tertiary Academic Hospital in northeast Italy. The primary outcome comprised arterial or venous thromboembolism or all-cause death within 30 days. Secondary outcomes comprised each single primary outcome component or major hemorrhagic event. Cox regression was used to determine predictors of the primary outcome and propensity score weights to balance the effect of heparin treatment on all outcomes. RESULTS: Data of 144 consecutive patients (age 70 ± 13, 33% females) were included in the study. High-dose prophylactic heparin was used in 69%, intermediate in 15%, and low in 17% of patients. The primary outcome occurred in 48 patients. Independent predictors of the primary outcome were COVID-19 severity (hazards ratio (HR) 1.96, 95% confidence interval (CI) 1.05-3.65, p = 0.035) and D-dimer levels (HR each log ng/dl 1.38, 95% CI 1.04-1.84, p = 0.026). Intermediate/high dose heparin did not affect the risk of the primary outcome compared with the low dose (weighted HR 1.39, 95% CI 0.75-2.56, p = 0.292). Intermediate/high heparin increased the risk of major hemorrhagic events (weighted HR 5.92, 95% CI 1.09-32, p = 0.039). CONCLUSIONS: In unvaccinated COVID-19 patients admitted to ED, prophylaxis with heparin at the intermediate/high dose did not reduce primary outcome compared with the low dose but increased the risk of major hemorrhagic events.


Тема - темы
COVID-19 , Venous Thromboembolism , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Emergency Service, Hospital , Female , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Hemorrhage/epidemiology , Heparin/adverse effects , Humans , Male , Middle Aged , Retrospective Studies , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
13.
Saudi Med J ; 43(7): 715-722, 2022 Jul.
Статья в английский | MEDLINE | ID: covidwho-1955133

Реферат

OBJECTIVES: To assess the effect of different thromboprophylaxis regimens on clinical outcomes and mortality of critical ill patients with coronavirus disease -19 (COVID-19). METHODS: We investigated the medical records of patients with positive COVID-19 (using polymerase chain reaction test) who were admitted to the intensive care unit (ICU) at Sakarya University Hospital, Sakarya, Turkey, from March 2020 to January 2021. We included patients under anticoagulant therapy in the clinical course. The patients were allocated to 3 groups: Group A - low-dose (prophylactic) low-molecular-weight-heparin (LMWH) therapy, Group B - high-dose (therapeutic) LMWH therapy, and patients that received aspirin additional to the high-dose (therapeutic) LMWH as Group C. Primary outcomes were overall mortality rates and length of stay (LOS) in ICU. Secondary outcomes were rates of major hemorrhagic and thrombotic events. RESULTS: Records of 475 patients were reviewed and 164 patients were included. No significant difference was detected in mortality rates between groups (p=0.135). Intensive care unit stay was 13 (9-24.5) days in Group A, 11 (8.75-23) days in Group B, and 13 (9-17) days in Group C without a significant difference (p=0.547). No significant difference was detected between groups in terms of thrombotic (p=0.565) and hemorrhagic events (p=0.615). CONCLUSION: A high-dose anticoagulation therapy and addition of aspirin to LMWH therapy did not decrease the mortality rates and LOS in ICU in critical ill COVID-19 patients. In addition, it did not increase the incidence of major hemorrhage and major thrombotic events.


Тема - темы
COVID-19 , Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Aspirin/therapeutic use , Critical Illness/therapy , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Retrospective Studies , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control
14.
BMJ ; 378: e070022, 2022 07 04.
Статья в английский | MEDLINE | ID: covidwho-1932663

Реферат

OBJECTIVE: To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital. MAIN OUTCOME MEASURES: Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework. RESULTS: 44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses. CONCLUSIONS: Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020173088.


Тема - темы
Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Bayes Theorem , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Hospitals , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic , Thrombosis/drug therapy , Venous Thromboembolism/drug therapy
15.
Intensive Care Med ; 48(8): 1039-1052, 2022 08.
Статья в английский | MEDLINE | ID: covidwho-1930382

Реферат

PURPOSE: To describe bleeding and thrombotic events and their risk factors in patients receiving extracorporeal membrane oxygenation (ECMO) for severe coronavirus disease 2019 (COVID-19) and to evaluate their impact on in-hospital mortality. METHODS: The ECMOSARS registry included COVID-19 patients supported by ECMO in France. We analyzed all patients included up to March 31, 2022 without missing data regarding bleeding and thrombotic events. The association of bleeding and thrombotic events with in-hospital mortality and pre-ECMO variables was assessed using multivariable logistic regression models. RESULTS: Among 620 patients supported by ECMO, 29% had only bleeding events, 16% only thrombotic events and 20% both bleeding and thrombosis. Cannulation site (18% of patients), ear nose and throat (12%), pulmonary bleeding (9%) and intracranial hemorrhage (8%) were the most frequent bleeding types. Device-related thrombosis and pulmonary embolism/thrombosis accounted for most of thrombotic events. In-hospital mortality was 55.7%. Bleeding events were associated with in-hospital mortality (adjusted odds ratio (adjOR) = 2.91[1.94-4.4]) but not thrombotic events (adjOR = 1.02[0.68-1.53]). Intracranial hemorrhage was strongly associated with in-hospital mortality (adjOR = 13.5[4.4-41.5]). Ventilation duration before ECMO ≥ 7 days and length of ECMO support were associated with bleeding. Thrombosis-associated factors were fibrinogen ≥ 6 g/L and length of ECMO support. CONCLUSIONS: In a nationwide cohort of COVID-19 patients supported by ECMO, bleeding incidence was high and associated with mortality. Intracranial hemorrhage incidence was higher than reported for non-COVID patients and carried the highest risk of death. Thrombotic events were less frequent and not associated with mortality. Length of ECMO support was associated with a higher risk of both bleeding and thrombosis, supporting the development of strategies to minimize ECMO duration.


Тема - темы
COVID-19 , Extracorporeal Membrane Oxygenation , Thrombosis , Anticoagulants/adverse effects , COVID-19/complications , COVID-19/therapy , Cohort Studies , Extracorporeal Membrane Oxygenation/adverse effects , Hemorrhage/chemically induced , Hemorrhage/etiology , Humans , Intracranial Hemorrhages/epidemiology , Intracranial Hemorrhages/etiology , Retrospective Studies , Thrombosis/epidemiology , Thrombosis/etiology
16.
Intern Emerg Med ; 17(6): 1817-1825, 2022 09.
Статья в английский | MEDLINE | ID: covidwho-1906506

Реферат

BACKGROUND: Hospitalized COVID-19 patients are at high risk of venous thromboembolism (VTE). Standard doses of anticoagulant prophylaxis may not be sufficiently effective for the prevention of VTE. The objective of this systematic-review and meta-analysis was to compare the efficacy and safety of high-dose versus low-dose thromboprophylaxis in hospitalized patients with COVID-19. MATERIAL AND METHODS: MEDLINE and EMBASE were searched up to October 2021 for randomized clinical trials (RCTs) comparing high-dose with low-dose thromboprophylaxis in hospitalized adult patients with COVID-19. The primary efficacy outcome was the occurrence of VTE and the primary safety outcome was major bleeding. RESULTS: A total of 5470 patients from 9 RCTs were included. Four trials included critically ill patients, four non-critically ill patients, and one included both. VTE occurred in 2.9% of patients on high-dose and in 5.7% of patients on low-dose thromboprophylaxis (relative risk [RR] 0.53; 95% confidence intervals [CIs], 0.41-0.69; I2 = 0%; number needed to treat for an additional beneficial outcome, 22). Major bleeding occurred in 2.5% and 1.4% of patients, respectively (RR 1.78; 95% CI, 1.20-2.66; I2 = 0%; number needed to treat for an additional harmful outcome, 100). All-cause mortality did not differ between groups (RR 0.97; 95% CI, 0.75-1.26; I2 = 47%). The risk of VTE was significantly reduced by high-dose thromboprophylaxis in non-critically ill (RR 0.54; 95% CI, 0.35-0.86; I2 = 0%), but not in critically ill patients (RR 0.69; 95% CI, 0.39-1.21; I2 = 36%). DISCUSSION: In hospitalized patients with COVID-19, high-dose thromboprophylaxis is more effective than low-dose for the prevention of VTE but increases the risk of major bleeding.


Тема - темы
COVID-19 , Venous Thromboembolism , Adult , Anticoagulants/therapeutic use , COVID-19/complications , Hemorrhage/chemically induced , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Venous Thromboembolism/epidemiology
17.
Eur J Clin Pharmacol ; 78(9): 1403-1420, 2022 Sep.
Статья в английский | MEDLINE | ID: covidwho-1899135

Реферат

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has shown unprecedented impact world-wide since the eruption in late 2019. Importantly, emerging reports suggest an increased risk of thromboembolism development in patients with COVID-19. Meanwhile, it is found that aspirin reduced mortality in critically ill patients with non-COVID-19 acute respiratory distress syndrome. Therefore, a meta-analysis was performed to investigate the effects of aspirin on COVID-19 mortality. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. Random effects models were used to calculate pooled relative risks (RRs) with 95% confidence intervals (Cis) to estimate the effect of aspirin on COVID-19 mortality. Relevant subgroup analyses and sensitivity analyses were also performed. RESULTS: The results showed that aspirin use was associated with a reduction in COVID-19 mortality (adjusted RR 0.69; 95% CI 0.50-0.95; P < 0.001). Subgroup analysis found that the low-dose group was associated with a reduced COVID-19 mortality (adjusted RR 0.64; 95% CI 0.48-0.85; P < 0.01). Aspirin use was associated with reduced COVID-19 mortality in Europe and America (crude RR 0.71; 95% CI 0.52-0.98; P = 0.04), and results from cohort studies suggested that aspirin use was a protective factor for COVID-19 mortality (adjusted RR 0.73; 95% CI 0.52-0.99; P = 0.04). Meanwhile, aspirin use was not associated with bleeding risk (crude RR 1.22; 95% CI 0.80-1.87; P = 0.96). CONCLUSIONS: This meta-analysis found that aspirin use was associated with a reduction in mortality in patients with COVID-19 and not with an increased risk of bleeding.


Тема - темы
Aspirin , COVID-19 , Aspirin/therapeutic use , COVID-19/drug therapy , Critical Illness , Hemorrhage/chemically induced , Humans , Pandemics
18.
J Bras Pneumol ; 48(4): e20220041, 2022.
Статья в английский, португальский | MEDLINE | ID: covidwho-1893706

Реферат

OBJECTIVE: To answer questions related to the use of anticoagulants in the treatment of COVID-19 patients. METHODS: This was a systematic review and meta-analysis of phase 3 randomized controlled trials comparing the use of anticoagulants in non-hospitalized and hospitalized COVID-19 patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to January 22, 2022. The risk of bias was assessed by the Cochrane risk-of-bias tool, and the quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: A total of 401 studies were initially selected. Of those, 9 met the inclusion criteria and were therefore analyzed (a total of 6,004 patients being analyzed). In non-hospitalized COVID-19 patients, no significant difference was found between post-discharge prophylactic anticoagulation and no intervention regarding venous thromboembolism or bleeding at 30 days. In hospitalized COVID-19 patients, full anticoagulation resulted in a slight reduction in thrombotic events at 30 days (risk difference, -0.03; 95% CI, -0.06 to -0.00; p = 0.04; I2 = 78%), the quality of evidence being moderate. However, no significant difference was found between full anticoagulation and no intervention regarding the risk of major bleeding, the quality of evidence being very low. No significant difference was found between intermediate- and standard-dose prophylactic anticoagulation (risk difference, -0.01; 95% CI, -0.07 to 0.06; p = 0.81; I2 = 0%), the quality of evidence being very low. CONCLUSIONS: Therapeutic anticoagulation appears to have no effect on mortality in COVID-19 patients, resulting in a slight reduction in venous thromboembolism in hospitalized patients.


Тема - темы
COVID-19 , Venous Thromboembolism , Aftercare , Anticoagulants/therapeutic use , COVID-19/drug therapy , Hemorrhage/chemically induced , Humans , Patient Discharge , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
19.
Int J Clin Pract ; 2022: 7325060, 2022.
Статья в английский | MEDLINE | ID: covidwho-1886811

Реферат

Background: Most evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19. Methods: Analysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses. Results: 7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM. Conclusion: Hospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399.


Тема - темы
Atrial Fibrillation , COVID-19 , Thromboembolism , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/drug therapy , COVID-19/drug therapy , Hemorrhage/chemically induced , Hospitalization , Hospitals , Humans , Prognosis , Registries , Thromboembolism/prevention & control
20.
J Thromb Thrombolysis ; 54(3): 431-437, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-1885483

Реферат

We observed multiple fatal intracranial hemorrhages shortly after initiating therapeutic anticoagulation for treatment of venous thromboembolism (VTE) in COVID-19 patients suggesting increased anticoagulation risk associated with COVID-19. The objective of this study is to quantify risk of major hemorrhage in hospitalized COVID-19 patients on therapeutic anticoagulation for deep venous thrombosis (DVT) or pulmonary embolism (PE). Hospitalized patients with COVID-19 receiving therapeutic anticoagulation for DVT, PE or both at four New York City hospitals were evaluated for hemorrhagic complications. These were categorized as major (including fatal) or clinically relevant non-major according to the criteria of the International Society of Thrombosis and Haemostasis. Hemorrhagic complications were correlated with clinical and laboratory data, ICD-10 code diagnoses and type of anticoagulation treatment. Minor hemorrhages were excluded. Major/clinically relevant hemorrhages occurred in 36 of 170 (21%) hospitalized COVID-19 patients being treated with therapeutic anticoagulation for VTE including 4 (2.4%) fatal hemorrhages. Hemorrhage was 3.4 times more likely with unfractionated heparin 27/76 (36%) compared to 8/81 (10%) with low molecular weight heparin (p = 0.002). Multivariate analysis showed that major hemorrhage was associated with intubation (p = 0.04) and elevated serum LDH (p < 0.001) and low fibrinogen (p = 0.05). Increased risk of hemorrhagic complications in treating VTE in hospitalized COVID-19 patients should be considered especially when using unfractionated heparin, in intubated patients, with low fibrinogen and/or elevated LDH. Checking serum fibrinogen and LDH before initiating therapeutic anticoagulation and monitoring coagulation parameters frequently may reduce bleeding complications.


Тема - темы
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Anticoagulants/adverse effects , COVID-19/complications , COVID-19/drug therapy , Fibrinogen/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pulmonary Embolism/drug therapy , Venous Thromboembolism/diagnosis
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