scholarly journals A Systematic Review and a Meta-Analysis Comparing Prophylactic and Therapeutic Low Molecular Weight Heparins for Mortality Reduction in 32,688 COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Riccardo Giossi ◽  
Danilo Menichelli ◽  
Arianna Pani ◽  
Elena Tratta ◽  
Alessandra Romandini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Low Molecular Weight ◽  
Full Dose ◽  
Prophylactic Dose ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Therapeutic Doses

Background: Antithrombotic treatment, including low molecular weight heparin (LMWH) or unfractionated heparin (UFH), has been proposed as a potential therapy for coronavirus disease 2019 (COVID-19) to lower diffuse intravascular clotting activation. However, it is unclear whether prophylactic or therapeutic doses have similar efficacy in reducing mortality.Methods: We performed a systematic review (PROSPERO registration CRD42020179955) and meta-analysis including observational cohort studies and randomized controlled trials (RCT) evaluating the effectiveness of heparins (either LMWH, UFH, or fondaparinux) in COVID-19 patients. Heparin treatment was compared to no anticoagulation. A subgroup analysis on prophylactic or therapeutic doses compared to no anticoagulation was performed. Prophylactic dose was also compared to full dose anticoagulation. Primary endpoint was all-cause mortality. Secondary endpoints were major bleeding and length of hospital stay (LOS).Results: 33 studies (31 observational, 2 RCT) were included for a total overall population of 32,688 patients. Of these, 21,723 (66.5%) were on heparins. 31 studies reported data on all-cause mortality, showing that both prophylactic and full dose reduced mortality (pooled Hazard Ratio [HR] 0.63, 95% confidence interval [CI] 0.57-0.69 and HR 0.56, 95% CI 0.47-0.66, respectively). However, the full dose was associated with a higher risk of major bleeding (Odds Ratio [OR] 2.01, 95% CI 1.14–3.53) compared to prophylactic dose. Finally, LOS was evaluated in 3 studies; no difference was observed between patients with and without heparins (0.98, −3.87, 5.83 days).Conclusion: Heparin at both full and prophylactic dose is effective in reducing mortality in hospitalized COVID-19 patients, compared to no treatment. However, full dose was associated with an increased risk of bleeding.Systematic Review Registration: https://clinicaltrials.gov/, identifier CRD42020179955

scholarly journals Low Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis

2019 ◽  
Vol 8 (12) ◽  
pp. 2039 ◽  
Author(s):  
Ruben J. Eck ◽  
Wouter Bult ◽  
Jørn Wetterslev ◽  
Reinold O. B. Gans ◽  
Karina Meijer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Sequential Analysis ◽  
Low Dose ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
Thrombosis Prophylaxis ◽  
Low Molecular Weight ◽  
All Cause Mortality

International guidelines recommend low-molecular-weight heparin (LMWH) as first-line pharmacological option for the prevention of venous thromboembolism (VTE) in many patient categories. Guidance on the optimal prophylactic dose is lacking. We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials to assess benefits and harms of low-dose LMWH versus placebo or no treatment for thrombosis prophylaxis in patients at risk of VTE. PubMed, Cochrane Library, Web of Science, and Embase were searched up to June 2019. Results were presented as relative risk (RR) with conventional and TSA-adjusted confidence intervals (CI). Forty-four trials with a total of 22,579 participants were included. Six (14%) had overall low risk of bias. Low-dose LMWH was not statistically significantly associated with all-cause mortality (RR 0.99; 95%CI 0.85–1.14; TSA-adjusted CI 0.89–1.16) but did reduce symptomatic VTE (RR 0.62; 95%CI 0.48–0.81; TSA-adjusted CI 0.44–0.89) and any VTE (RR 0.61; 95%CI 0.50–0.75; TSA-adjusted CI 0.49–0.82). Analyses on major bleeding (RR 1.07; 95%CI 0.72–1.59), as well as serious adverse events (SAE) and clinically relevant non-major bleeding were inconclusive. There was very low to moderate-quality evidence that low-dose LMWH for thrombosis prophylaxis did not decrease all-cause mortality but reduced the incidence of symptomatic and asymptomatic VTE, while the analysis of the effects on bleeding and adverse events remained inconclusive.

scholarly journals Intermediate Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis

2019 ◽  
Vol 45 (08) ◽  
pp. 810-824 ◽  
Author(s):  
Ruben J. Eck ◽  
Wouter Bult ◽  
Jørn Wetterslev ◽  
Reinold O.B. Gans ◽  
Karina Meijer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Risk Of Bias ◽  
Sensitivity Analyses ◽  
Thrombosis Prophylaxis ◽  
Low Molecular Weight ◽  
All Cause Mortality ◽  
Intermediate Dose

AbstractDifferent doses of low-molecular-weight heparin (LMWH) are registered and used for thrombosis prophylaxis. We assessed benefits and harms of thrombosis prophylaxis with a predefined intermediate-dose LMWH compared with placebo or no treatment in patients at risk of venous thromboembolism (VTE). We performed a systematic review with meta-analyses and trial sequential analyses (TSA) following The Cochrane Handbook for Systematic Reviews of Interventions. Medline, Cochrane CENTRAL, Web of Science, and Embase were searched up to December 2018. Trials were evaluated for risk of bias and quality of evidence was assessed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Seventy randomized trials with 34,046 patients were included. Eighteen (26%) had overall low risk of bias. There was a small statistically significant effect of LMWH on all-cause mortality (risk ratio [RR]: 0.96; TSA-adjusted confidence interval [TSA-adjusted CI]: 0.94–0.98) which disappeared in sensitivity analyses excluding ambulatory cancer patients (RR: 0.99; TSA-adjusted CI: 0.84–1.16). There was moderate-quality evidence for a statistically significant beneficial effect on symptomatic VTE (odds ratio [OR]: 0.59; TSA-adjusted CI: 0.53–0.67; number needed to treat [NNT]: 76; 95% CI: 60–106) and a statistically significant harmful effect on major bleeding (Peto OR: 1.66; TSA-adjusted CI: 1.31–2.10; number needed to harm [NNH]: 212; 95% CI: 142–393). There were no significant intervention effects on serious adverse events. The use of intermediate-dose LMWH for thrombosis prophylaxis compared with placebo or no treatment was associated with a small statistically significant reduction of all-cause mortality that disappeared in sensitivity analyses excluding trials that evaluated LMWH for anticancer treatment. Intermediate-dose LMWH provides benefits in terms of VTE prevention while it increases major bleeding.

Low molecular weight heparin (LMWH) for primary thrombophylaxis in patients with solid malignancies: Systematic review and meta-analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20595-e20595
Author(s):  
Irit Ben-Aharon ◽  
Salomon M. Stemmer ◽  
Ofer Shpilberg ◽  
Aaron Sulkes ◽  
Anat Gafter-Gvili
Keyword(s):  
Molecular Weight ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Primary Prophylaxis ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Low Molecular Weight ◽  
Solid Malignancies ◽  
Increased Risk

e20595 Background: Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism (VTE). The role of low molecular weight heparin (LMWH) as antithrombotic prophylaxis has been appraised in several studies, yielding conflicting results. We performed a meta-analysis of all randomized controlled trials (RCTs) which evaluated the addition of LMWH as primary prophylaxis in patients with solid malignancies while receiving chemotherapy. Methods: RCTs were identified by searching the Cochrane Library, MEDLINE databases and conference proceedings. Relative risks (RR) of thrombotic events, mortality as well as adverse events were estimated and pooled. Results: Nine trials met the inclusion criteria, and evaluated a total of 6691 patients. Primary prophylaxis with LMWH reduced both symptomatic VTEs: (RR 0.47, 95% CI(0.32 to 0.69)) and the rate of pulmonary embolism(PE): (RR 0.51, 95% CI(0.30 to 0.86)).Symptomatic DVT was reduced as well (RR 0.35, 95% CI(0.21 to 0.60). Meta-analysis of six trials which reported survival outcomes revealed no statistically significant benefit for LMWH in 1 year mortality rates (RR 0.93, 95% CI(0.83 to1.04)). There was no significant increase in major bleeding events. Conclusions: LMWH reduces the incidence of symptomatic VTE and PE in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. Nevertheless, LMWH had no significant effect on survival outcomes. Future studies should delineate whether specific populations may derive a survival benefit from LMWH primary prophylaxis.

Low Molecular Weight Heparin and Bleeding in Patients with Severe Renal Failure: A Meta-Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 907-907
Author(s):  
Wendy Lim ◽  
Francesco Dentali ◽  
John Eikelboom ◽  
Mark A. Crowther
Keyword(s):  
Molecular Weight ◽  
Renal Function ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Low Molecular Weight ◽  
Severe Renal Failure ◽  
Increased Risk ◽  
Standard Weight

Abstract Background: Dose adjustment or monitoring of low molecular weight heparin (LMWH) is commonly recommended in patients with severe renal insufficiency (creatinine clearance [CrCl] ≤ 30 ml/min) but little evidence supports this recommendation. Purpose: To compare the risk of major bleeding in LMWH-treated patients with CrCl ≤ 30 ml/min versus > 30 ml/min using standard weight-adjusted therapeutic LMWH doses, empirically adjusted LMWH doses and prophylactic LMWH doses. Data sources: Electronic databases (MEDLINE, EMBASE, Cochrane Library), reference lists and contact with experts. Study selection: Observational or subgroups of randomized studies that included non-dialyzed patients with varying degrees of renal function who were treated with LMWH and which reported CrCl and major bleeding. Data extraction: Two reviewers independently selected studies and extracted data on patient characteristics, renal function, LMWH treatment and major bleeding. The pooled relative risk (RR) of major bleeding in patients with CrCl ≤ 30 versus > 30 ml/min was calculated by the Mantel-Haenszel method. Data synthesis: In 12 studies involving 4971 patients (10 studies of 4741 patients using enoxaparin; 2 studies of 230 patients using tinzaparin), LMWH significantly increased the risk of major bleeding in patients with CrCl ≤ 30 compared with > 30 ml/min (5.0% vs. 2.4%, RR 2.34, 95% confidence interval [CI]: 1.46 to 3.74; P = 0.0004; number needed to harm [NNH] = 38). When analyzed according to LMWH preparation, increased major bleeding was evident in studies of standard weight-adjusted therapeutic dose enoxaparin (8.3% vs. 2.4%, RR 2.96; 95% CI: 1.63 to 5.37, NNH = 17) but not in studies using empirically adjusted enoxaparin doses (0.9% vs. 1.9%, RR 1.06; 95% CI: 0.23 to 4.97), P for heterogeneity = 0.82. There were insufficient studies using tinzaparin and prophylactic doses of enoxaparin. Limitations: Only 2 LMWH preparations were evaluated and only 2 studies used tinzaparin. Data are observational and the potential for confounding cannot be excluded. Conclusions: Non-dialysis dependent patients with CrCl ≤ 30 ml/min who are treated with therapeutic doses of enoxaparin have an increased risk of major bleeding. Empiric dose reduction of enoxaparin may reduce the risk of bleeding and merits further evaluation. No conclusions can be drawn regarding other LMWHs.

“direct Oral Anticoagulants Versus Low-molecular-weight Heparin for Acute Treatment of Venous Thromboembolism in Patients With Gastrointestinal Cancer: a Systematic Review and Meta-analysis”

2021 ◽  
Author(s):  
Tarinee Rungjirajittranon ◽  
Weerapat Owattanapanich ◽  
Yingyong Chinthammitr ◽  
Theera Ruchutrakool ◽  
Bundarika Suwanawiboon
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Gi Cancer ◽  
Cancer Associated Thrombosis

Abstract BackgroundThe association between gastrointestinal (GI) cancer and a high incidence of venous thromboembolism (VTE) is well known. Previous randomized controlled studies demonstrated that direct oral anticoagulants (DOACs) effectively treat cancer-associated VTE (CAT). However, some DOACs appeared to increase the risk of bleeding, particularly in patients with GI malignancies. Therefore, the current systematic review and meta-analysis was conducted to evaluate the safety and efficacy of DOACs in GI cancer-associated thrombosis.MethodsAll relevant studies that compared DOACs and low-molecular-weight heparin (LMWH) in GI cancer-associated thrombosis that were published before December 2020 were individually searched in two databases (MEDLINE and EMBASE) by two investigators. The effect estimates and 95% confidence intervals (CI) from each eligible study were combined using the Mantel-Haenszel method.ResultsA total of 1,418 patients were included in this meta-analysis. The rate of major bleeding was not significantly different between groups (relative risk [RR]: 1.57, 95% CI: 0.93-2.65, P=0.09, I2=34%). However, the rate of clinically relevant non-major bleeding (CRNMB) was significantly higher in the DOACs group (RR: 1.98, 95% CI: 1.34-2.91, P=0.0005, I2=0%). The risk of recurrent VTE was not significantly different between groups (RR: 0.72, 95% CI: 0.41-1.28, P=0.27, I2=0%).ConclusionsThe current data suggests that treatment of GI cancer-associated thrombosis with DOACs significantly increases the risk of CRNMB, and a trend towards major bleeding risk in DOACs group. The efficacy of DOACs for preventing recurrent VTE in GI cancer was comparable to that of LMWHs.Trial registration: INPLASY202180113

scholarly journals Safety of Dabigatran as an Anticoagulant: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ya Zhou ◽  
Zhihao Yao ◽  
Linjie Zhu ◽  
Yong Tang ◽  
Jie Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Intracranial Hemorrhage ◽  
Major Bleeding ◽  
Adverse Reactions ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Suitable Alternative ◽  
Increased Risk ◽  
All Cause Mortality

Background: Dabigatran is a univalent low-molecular-weight direct thrombin inhibitor which was developed as an alternative to vitamin K antagonists (VKAs). However, the safety of dabigatran remains controversial so far. In this study, we aimed to compare the risk of bleeding, fatal adverse events, and the all-cause mortality of dabigatran with those of the control group by a systematic review and meta-analysis of randomized controlled trials.Methods: We systematically searched PubMed, Web of Science, Cochrane Library, Medline, Embase, Wanfang database, Clinical trial, China National Knowledge Infrastructure Chinese Scientific Journal database (VIP), and Chinese Biological Medicine database (CBM), for clinical trials on conventional treatments compared with dabigatran, published between January 2014 and July 2020. The reported outcomes, including the endpoints of primary safety, were systematically investigated.Results: Seven RCTs (n = 10,743) were included in the present systematic review. Compared to the control groups, dabigatran was not associated with an increased risk of major bleeding (relative risk [RR] 0.86, 95% confidence interval [CI]: 0.61 to 1.21, p = 0.06), intracranial hemorrhage (RR 0.89, 95% CI: 0.58 to 1.36, p = 0.41), fatal adverse reactions (RR 0.87, 95% CI: 0.65 to 1.17, p = 0.66), all-cause mortality (RR 0.88, 95% CI: 0.70 to 1.11, p = 0.45, I2 = 0%), and significantly reduced risk of clinically relevant non-major bleeding (RR 0.96, 95% CI: 0.65 to 1.42, p = 0.0007). However, dabigatran is associated with an increased risk of gastrointestinal (GI) bleeding (RR 1.78, 95% CI: 1.02 to 3.13, p = 0.05).Conclusion: Dabigatran has a favorable safety profile in terms of major bleeding, intracranial hemorrhage, and life-threatening events, among other safety outcomes. The present study suggested that dabigatran may be a suitable alternative to VKAs as an oral anticoagulant. However, more data are necessary to clarify the incidence of other adverse events and serious adverse reactions.

scholarly journals Prediction of all-cause mortality with malnutrition assessed by controlling nutritional status score in patients with heart failure: a systematic review and meta-analysis

2021 ◽  
pp. 1-8
Author(s):  
Huiyang Li ◽  
Peng Zhou ◽  
Yikai Zhao ◽  
Huaichun Ni ◽  
Xinping Luo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Nutritional Status ◽  
Meta Analysis ◽  
Predictive Values ◽  
Increased Risk ◽  
Patients With Heart Failure ◽  
All Cause Mortality ◽  
Conut Score

Abstract Objective: The aim of this meta-analysis was to investigate the association between malnutrition assessed by the controlling nutritional status (CONUT) score and all-cause mortality in patients with heart failure. Design: Systematic review and meta-analysis. Settings: A comprehensively literature search of PubMed and Embase databases was performed until 30 November 2020. Studies reporting the utility of CONUT score in prediction of all-cause mortality among patients with heart failure were eligible. Patients with a CONUT score ≥2 are grouped as malnourished. Predictive values of the CONUT score were summarized by pooling the multivariable-adjusted risk ratios (RR) with 95 % CI for the malnourished v. normal nutritional status or per point CONUT score increase. Participants: Ten studies involving 5196 patients with heart failure. Results: Malnourished patients with heart failure conferred a higher risk of all-cause mortality (RR 1·92; 95 % CI 1·58, 2·34) compared with the normal nutritional status. Subgroup analysis showed the malnourished patients with heart failure had an increased risk of in-hospital mortality (RR 1·78; 95 % CI 1·29, 2·46) and follow-up mortality (RR 2·01; 95 % CI 1·58, 2·57). Moreover, per point increase in CONUT score significantly increased 16% risk of all-cause mortality during the follow-up. Conclusions: Malnutrition defined by the CONUT score is an independent predictor of all-cause mortality in patients with heart failure. Assessment of nutritional status using CONUT score would be helpful for improving risk stratification of heart failure.

scholarly journals Tinzaparin Safety in Patients With Cancer and Renal Impairment: A Systematic Review

2021 ◽  
Vol 27 ◽  
pp. 107602962097959
Author(s):  
I. A. Vathiotis ◽  
N. K. Syrigos ◽  
E. P. Dimakakos
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Severe Renal Impairment ◽  
Special Populations ◽  
Low Molecular Weight ◽  
Patients With Cancer

Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. Tinzaparin is the low-molecular-weight heparin with the highest average molecular weight. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin, prescribed either as a prophylactic or as a therapeutic regimen for venous thromboembolism in special populations, including cancer patients and patients with renal impairment. We identified prospective studies up to August 2020 reporting safety outcomes for cancer patients and patients with renal impairment on tinzaparin regimens. In patients with cancer major bleeding rates fluctuated between 0.8% and 7%. Patients on tinzaparin exhibited significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin was not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin did not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients with renal impairment on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 3.4% of cases; major bleeding rates were higher for cancer patients with renal impairment on therapeutic tinzaparin regimens (4.3 to 10%). Tinzaparin can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a safe choice for special populations at increased risk for thrombosis and bleeding.

scholarly journals Renin-angiotensin system blocker and outcomes of COVID-19: a systematic review and meta-analysis

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-215322
Author(s):  
Hyun Woo Lee ◽  
Chang-Hwan Yoon ◽  
Eun Jin Jang ◽  
Chang-Hoon Lee
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Severe Disease ◽  
Renin Angiotensin System ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Receptor Blockers

BackgroundThe association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19.MethodsWe searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease.ResultsACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I2=95%, low certainty of evidence).ConclusionsACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.

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