scholarly journals High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (23) ◽  
pp. 5549
Author(s):  
Anastasios Kollias ◽  
Konstantinos G. Kyriakoulis ◽  
Ioannis P. Trontzas ◽  
Vassiliki Rapti ◽  
Ioannis G. Kyriakoulis ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Therapeutic Dose ◽  
Survival Benefit ◽  
Meta Analysis ◽  
Hospitalized Patients ◽  
Bleeding Events ◽  
Prophylactic Dose ◽  
Major Bleeding Events

Thromboprophylaxis in hospitalized patients with COVID-19 has been associated with a survival benefit and is strongly recommended. However, the optimal dose of thromboprophylaxis remains unclear. A systematic review and meta-analysis (PubMed/EMBASE) of studies comparing high (intermediate or therapeutic dose) versus standard (prophylactic dose) intensity of thrombo-prophylaxis with regard to outcome of hospitalized patients with COVID-19 was performed. Randomized and non-randomized studies that provided adjusted effect size estimates were included. Meta-analysis of 7 studies comparing intermediate versus prophylactic dose of thromboprophylaxis (2 randomized and 5 observational, n = 2009, weighted age 61 years, males 61%, ICU 53%) revealed a pooled adjusted relative risk (RR) for death at 0.56 (95% confidence intervals (CI) 0.34, 0.92) in favor of the intermediate dose. For the same comparison arms, the pooled RR for venous thromboembolism was 0.84 (95% CI 0.54, 1.31), and for major bleeding events was 1.63 (95% CI 0.79, 3.37). Meta-analysis of 17 studies comparing therapeutic versus prophylactic dose of thromboprophylaxis (2 randomized and 15 observational, n = 7776, weighted age 64 years, males 54%, ICU 21%) revealed a pooled adjusted RR for death at 0.73 (95% CI 0.47, 1.14) for the therapeutic dose. An opposite trend was observed in the unadjusted analysis of 15 observational studies (RR 1.24 (95% CI 0.88, 1.74)). For the same comparison arms, the pooled RR for venous thromboembolism was 1.13 (95% CI 0.52, 2.48), and for major bleeding events 3.32 (95% CI 2.51, 4.40). In conclusion, intermediate compared with standard prophylactic dose of thromboprophylaxis appears to be rather safe and is associated with additional survival benefit, although most data are derived from observational retrospective analyses. Randomized studies are needed to define the optimal thromboprophylaxis in hospitalized patients with COVID-19.

scholarly journals Risk of major bleeding during extended oral anticoagulation in patients with first unprovoked venous thromboembolism: a systematic review and meta-analysis protocol

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Faizan Khan ◽  
Miriam Kimpton ◽  
Tobias Tritschler ◽  
Grégoire Le Gal ◽  
Brian Hutton ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Bleeding Events ◽  
Major Bleeding Events

Abstract Background The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE. Methods Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis. Discussion The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE. Systematic review registration PROSPERO CRD42019128597.

Primary Venous Thromboembolism Prophylaxis in Patients with Solid Tumors Receiving Chemotherapy: A Meta-Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1157-1157
Author(s):  
Minh Phan ◽  
Sonia John ◽  
Ana Isabel Casanegra ◽  
Alfonso Tafur
Keyword(s):  
Venous Thromboembolism ◽  
Solid Tumors ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Mortality Data ◽  
Significant Heterogeneity ◽  
Bleeding Events ◽  
Vte Prophylaxis ◽  
Major Bleeding Events ◽  
Pharmacological Thromboprophylaxis

Abstract Abstract 1157 Background: Venous thromboembolism [VTE] is the second highest cause of mortality among patients with cancer. However, pharmacological thromboprophylaxis for patients with solid tumor is only recommended during hospitalization. Primary outpatient thromboprophylaxis is not a widely accepted practice. Objective: Determine safety and efficacy of outpatient primary VTE prophylaxis in patients with solid tumors. Data sources: A systematic review was conducted using MEDLINE and EMBASE up to June 2012. Key search words included venous thromboembolism, malignancy, anticoagulants, and chemotherapy. Studies were considered for our meta-analysis if they included outpatient primary pharmacological thromboprophylaxis in adult patients with active solid cancer. All the information was independently reviewed by 2 of the authors [MP, SJ] and a third reviewer resolved discrepancies. The measure of association was calculated with R (R: A Language and Environment for Statistical, R Development Core Team, www.R-project.org), R META package (Version 0.8–2, Author: Guido Schwarzer). The Q statistic was calculated and a formal test of homogeneity was conducted. Random-effects model was preferred in case of heterogeneity. Results: A total of 1371 abstracts were reviewed and 29 manuscripts were fully abstracted. Eight randomized controlled trials including 6706 patients were analyzed. There were less VTE events with outpatient prophylaxis: odds ratio [OR] of 0.53 (95% CI, 0.40–0.70). Six studies used low or ultra-low molecular weight heparin and two studies used warfarin. In the subgroup analysis of heparin based primary prophylaxis, there was a significant reduction in VTE events [OR 0.47, 95% CI, 0.34–0.64], no significant heterogeneity [FIG 1]. In addition, there was no difference in major bleeding events between groups [OR 1.48, 95% CI, 0.89–2.46]. Five studies reported mortality data; there was significant heterogeneity between studies. Conclusions: Heparin based outpatient VTE prophylaxis in patients with solid tumors reduced by half the risk of VTE with no significant differences in major bleeding events. The current publications do not allow a meaningful grouped analysis of survival data, improved patient selection is necessary in order to adequately target VTE prevention strategies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Rivaroxaban for cancer-associated venous thromboembolism

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110121
Author(s):  
Bo Liang ◽  
Yi Liang ◽  
Li-Zhi Zhao ◽  
Yu-Xiu Zhao ◽  
Ning Gu
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Efficacy And Safety ◽  
China National Knowledge Infrastructure ◽  
Bleeding Events ◽  
Significant Difference ◽  
Major Bleeding Events

All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from cancer-associated VTE. However, there is still a debate about whether the new oral anticoagulant, rivaroxaban, can bring better efficacy and safety outcomes globally. Thus, this systematic review and meta-analysis was conducted to evaluate the efficacy and safety of rivaroxaban. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure for relevant published papers before 1 September 2019, with no language restrictions. The primary outcomes are defined as the recurrence of VTE. The secondary outcomes are defined as clinically relevant non-major bleeding, adverse major bleeding events, and all-cause of death. The data were analyzed by Stata with risk ratio (RR) and 95% confidence interval (CI). Four trials encompassing 1996 patients were included. Rivaroxaban reduced recurrent VTE with no significant difference (RR = 0.68, 95% CI = 0.43–1.07). Similarly, there were no significant differences in adverse major bleeding events (RR = 0.86, 95% CI = 0.37–2.00), clinically relevant non-major bleeding (RR = 1.24, 95% CI = 0.73–2.12) and all-cause mortality (RR = 0.76, 95% CI = 0.40–1.44). In a selected study population of cancer patients with VTE, rivaroxaban is as good as other anticoagulants. Further, carefully designed randomized controlled trials should be performed to confirm these results.

Major bleeding rates after prophylaxis against venous thromboembolism: Systematic review, meta-analysis, and cost implications

2004 ◽  
Vol 20 (4) ◽  
pp. 405-414 ◽  
Author(s):  
James Muntz ◽  
David A Scott ◽  
Adam Lloyd ◽  
Matthias Egger
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Bleeding Events ◽  
Relative Risks ◽  
Major Orthopedic Surgery ◽  
Anticoagulant Prophylaxis ◽  
Mean Cost

Objectives: The frequency and consequences of major bleeding associated with anticoagulant prophylaxis for prevention of venous thromboembolism is examined.Methods: We conducted a systematic review and meta-analysis of controlled trials that reported rates of major bleeding after pharmaceutical thromboprophylaxis in patients undergoing major orthopedic surgery. Thromboprophylactic agents were divided into four groups:warfarin/other coumarin derivatives (WARF), unfractionated heparin (UFH), low molecular weight heparin (LMWH), and pentasaccharide (PS). Meta-analysis was conducted comparing LMWH with each of WARF, UFH, and PS. The frequency of re-operation due to major bleeding was reviewed and combined with published costs to estimate the mean cost of managing major bleeding events in these patients.Results: Twenty-one studies including 20,523 patients met inclusion criteria for the meta-analysis. No evidence of significant between-trial heterogeneity in risk ratios was found. Combined (fixed effects) relative risks (RR) of major bleeding compared with LMWH were WARF – RR 0.59 (95 percent confidence interval [CI], 0.44–0.80); UFH – RR 1.52 (95 percent CI, 1.04–2.23); PS – RR 1.52 (95 percent CI, 1.11–2.09). Seventy-one studies including 32,433 patients were included in the review of consequences of major bleeding. We estimated that the average cost of major bleeding is $113 per patient receiving thromboprophylaxis.Conclusions: LMWH results in fewer major bleeding episodes than UFH and PS but more than WARF. These events are costly and clinically important.

scholarly journals Effect of Anticoagulant Administration on the Mortality of Hospitalized Patients With COVID-19: An Updated Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Luojia Jiang ◽  
Yupei Li ◽  
Heyue Du ◽  
Zheng Qin ◽  
Baihai Su
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Anticoagulation Therapy ◽  
Hospitalized Patients ◽  
Severe Bleeding ◽  
Bleeding Events ◽  
Assessment Development ◽  
Dichotomous Variables ◽  
Lower Mortality Risk

Background: Anticoagulation is generally used in hospitalized patients with coronavirus disease 2019 (COVID-19) as thromboprophylaxis. However, results from different studies comparing the effect of anticoagulation on the mortality of COVID-19 patients with non-anticoagulation are inconclusive.Methods: Our systematic review included observational trials if they studied anticoagulant therapy in hospitalized patients with COVID-19 for mortality or bleeding events. Dichotomous variables from individual studies were pooled by risk ratio (RR) and their 95% confidence interval (95% CI) using the random-effects model. Grading of Recommendations Assessment, Development and Evaluation was used to assess the quality of evidence.Results: A total of 11 observational studies enrolling 20,748 hospitalized COVID-19 patients overall were included. A pooled meta-analysis of these studies showed that anticoagulation therapy, compared with non-anticoagulation therapy, was associated with lower mortality risk (RR 0.70, 95% CI 0.52–0.93, p = 0.01). The evidence of benefit was stronger among critically ill COVID-19 patients in the intensive care units (RR 0.59, 95% CI 0.43–0.83, p = 0.002). Additionally, severe bleeding events were not associated with the administration of anticoagulants (RR 0.93, 95% CI 0.71–1.23, p = 0.63).Conclusion: Among patients with COVID-19 admitted to hospital, the administration of anticoagulants was associated with a decreased mortality without increasing the incidence of bleeding events.

Societal costs of venous thromboembolism and subsequent major bleeding events: a national register-based study

2019 ◽  
Vol 6 (2) ◽  
pp. 130-137
Author(s):  
Nina Gustafsson ◽  
Peter Bo Poulsen ◽  
Sandra Elkjær Stallknecht ◽  
Lars Dybro ◽  
Søren Paaske Johnsen
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Home Care Services ◽  
Care Hospital ◽  
Bleeding Events ◽  
Societal Costs ◽  
Vein Thrombosis ◽  
Primary Care Hospital ◽  
Major Bleeding Events ◽  
The Impact

Abstract Aims Detailed evidence on the societal costs of venous thromboembolism (VTE), i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE), and of subsequent major bleeding events, e.g. intracranial and gastrointestinal bleedings, is limited. The objective was to estimate the average 3-year societal event costs attributable to VTE and subsequent major bleedings in Denmark. Methods and results Based on nationwide Danish registers, each incident patient diagnosed with VTE in the period from 2004 to 2016 was identified and matched with four non-VTE patients by nearest-neighbour propensity score matching. For bleeding patients, the reference cohort was VTE patients without bleedings. Event costs in terms of VTE, DVT, PE, and major bleedings in VTE patients were measured by the ‘difference-in-actual-cost’ method within 3 years after the incidence. Societal costs included healthcare costs (primary care, hospital, and prescription medicine), municipality home care services, and production loss. The study population included 74 137 VTE incident patients (DVT: 43 099; PE: 31 038), and 4887 VTE patients with a major bleeding within 3 years from VTE diagnosis. The 3-year attributable societal VTE event costs were 40 024 EUR (DVT: 34 509 EUR; PE: 50 083 EUR) with 53% of these costs appearing in the first incident year. Similar results for major bleedings were 51 168 EUR with 46% of these costs appearing in the first incident year. Conclusion The societal costs of VTE and subsequent major bleedings are substantial and ought to be considered. Estimated costs of events may be informative in evaluating the impact of preventive interventions targeting VTE and subsequent major bleedings.

scholarly journals Prophylactic anticoagulant therapy decreases the incidence of deep vein thrombosis in patients with solid tumors: A systematic review and meta-analysis

2017 ◽  
Vol 7 (1) ◽  
pp. 35
Author(s):  
Yunjiao Zhou ◽  
Gong Yang ◽  
Chenglei Huang
Keyword(s):  
Systematic Review ◽  
Deep Vein Thrombosis ◽  
Solid Tumors ◽  
Risk Ratio ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Bleeding Events ◽  
Vein Thrombosis ◽  
And Control ◽  
Deep Vein

It is not well understood the efficacy and safety of primary deep vein thrombosis (DVT) prophylaxis of anticoagulants in patients with solid tumors. This systematic review and meta-analysis of randomized controlled trials (RCT) determines the relative ratio of primary DVT, survival rate and bleeding events among patients with solid tumors treated with anticoagulants or placebo. Comprehensive literature searches were conducted through the Pubmed, Ovid MEDLINE and EMBASE databases published from January 1st, 1993 to December 31st, 2015. Statistical analysis was performed by RevMan 5.0 software. For DVT events, therisk ratio in 16 trials between the prophylactic and control patients was statistically significant at 0.45 [0.36-0.58]; for major bleeding events, the risk ratio in 18 trials between the prophylactic and control patients was not statistically significant at 1.33 [0.99-1.79], while that in 15 trials with clinically relevant non-major bleeding was statistically significant at 1.83 [1.46-2.30]; the risk ratio for the mortality rate of patients with solid tumors in 16 trials was not statistically significant at 0.97 [0.93-1.02]. Inconclusion, the risk ratio in this meta-analysis showed a significantly reduced incidence of DVT with anticoagulant use. Treatment to patients who had solid tumors with prophylactic anticoagulants enhanced the incidence rate of non-major bleeding but has no significant impact on the incidence rate of major bleeding. No significant differences were found in the mortality outcomes between anticoagulant and non-anticoagulant groups.

Calculation of HAS-BLED Score Is Useful for Early Identification of Venous Thromboembolism Patients at High Risk for Major Bleeding Events: A Prospective Outpatients Cohort Study

2017 ◽  
Vol 44 (04) ◽  
pp. 348-352 ◽  
Author(s):  
Reinhard Raggam ◽  
Franz Hafner ◽  
Alexander Avian ◽  
Gerald Hackl ◽  
Gerhard Cvirn ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Odds Ratio ◽  
Bleeding Complications ◽  
Minor Bleeding ◽  
Prospective Evaluation ◽  
Bleeding Events ◽  
Increased Risk ◽  
Major Bleeding Events

AbstractThe aim of this study was prospective evaluation of the performance of the HAS-BLED score in predicting major bleeding complications in a real-world outpatient cohort, during long-term anticoagulation for venous thromboembolism (VTE), treated with a broad spectrum of anticoagulants. We analyzed 111 outpatients objectively diagnosed with VTE and treated long-term with various anticoagulants. Patients were grouped in three cohorts based on the anticoagulant regimen. Calculation of the HAS-BLED score and documentation of bleeding events were performed every 6 months for 1 year. Patients with a HAS-BLED score ≥ 3 had an increased risk for major bleeding events (odds ratio [OR]: 13.05, 95% confidence interval [CI]: 0.96–692.58, p = 0.028) and a trend to higher risk for minor bleeding events as well (OR: 2.25, 95% CI: 0.87–5.85, p = 0.091) when compared with patients with a HAS-BLED score < 3.This indicates that a HAS-BLED score ≥ 3 allows for identification of patients with VTE on long-term anticoagulation at an increased risk for major bleeding events, irrespective of the anticoagulant agent used.

Racial Differences in Ischaemia/Bleeding Risk Trade-Off during Anti-Platelet Therapy: Individual Patient Level Landmark Meta-Analysis from Seven RCTs

2018 ◽  
Vol 119 (01) ◽  
pp. 149-162 ◽  
Author(s):  
Jeehoon Kang ◽  
Kyung Park ◽  
Tullio Palmerini ◽  
Gregg Stone ◽  
Michael Lee ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Meta Analysis ◽  
Bleeding Risk ◽  
Bleeding Events ◽  
East Asians ◽  
Trade Off ◽  
Individual Patient Level ◽  
Patient Level ◽  
Anti Platelet Therapy ◽  
Major Bleeding Events

Background Prolonged dual anti-platelet therapy (DAPT) is intended to reduce ischaemic events, at the cost of an increased bleeding risk in patients undergoing percutaneous coronary intervention (PCI). In this study, we evaluated whether race influences the ischaemia/bleeding risk trade-off. Methods We searched for randomized clinical trials (RCTs) comparing DAPT duration after PCI. To compare the benefit or harm between DAPT duration by race, individual patient-level landmark meta-analysis was performed after discontinuation of the shorter duration DAPT group in each RCT. The primary ischaemic endpoint was major adverse cardiac events (MACEs), and the primary bleeding endpoint was major bleeding events (clinicaltrials.gov NCT03338335). Results Seven RCTs including 16,518 patients (8,605 East Asians, 7,913 non-East Asians) were pooled. MACE occurred more frequently in non-East Asians (0.8% vs. 1.8%, p < 0.001), while major bleeding events occurred more frequently in East Asians (0.6% vs. 0.3%, p = 0.001). In Cox proportional hazards model, prolonged DAPT significantly increased the risk of major bleeding in East Asians (hazard ratio [HR], 2.843, 95% confidence interval [CI], 1.474–5.152, p = 0.002), but not in non-East Asians (HR, 1.375, 95% CI, 0.523–3.616, p = 0.523). East Asians had a higher median probability risk ratio of bleeding to ischaemia (0.66 vs. 0.15), and the proportion of patients with higher probability of bleeding than ischaemia was significantly higher in East Asians (32.3% vs. 0.4%, p < 0.001). Conclusion We suggest that the ischaemia/bleeding trade-off may be different between East Asians and non-East Asians. In East Asians, prolonged DAPT may have no effect in reducing the ischaemic risk, while significantly increases the bleeding risk.

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