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.

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 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

“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 and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
N Hussain ◽  
S Adeel Hassan ◽  
S Mandava ◽  
F Yasmin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Efficacy And Safety ◽  
Dichotomous Data ◽  
Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and  DOACs in the management of malignancy induced  VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November  28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05.  Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs  (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p > 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

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.

Intermediate doses of low-molecular-weight heparin for the long-term treatment of pregnancy thromboembolism. A systematic review

2014 ◽  
Vol 111 (03) ◽  
pp. 559-561 ◽  
Author(s):  
Esteban Gándara ◽  
Marc Carrier ◽  
Marc Rodger
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Term Treatment ◽  
Low Molecular Weight ◽  
Contact Information ◽  
Long Term Treatment ◽  
E Mail

Note: The contact information for Drs. Gandara and Carrier is the same as for Dr. Rodger. Their e-mail addresses are [email protected] and [email protected], respectively.

scholarly journals Efficacy, Safety, and Timing of Anticoagulant Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients With Acute Spinal Cord Injury: A Systematic Review

2017 ◽  
Vol 7 (3_suppl) ◽  
pp. 138S-150S ◽  
Author(s):  
Paul M. Arnold ◽  
James S. Harrop ◽  
Geno Merli ◽  
Lindsay G. Tetreault ◽  
Brian K. Kwon ◽  
...  
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Lower Risk ◽  
Low Molecular Weight Heparin ◽  
Inferior Vena Cava Filter ◽  
Inferior Vena ◽  
Vena Cava ◽  
Low Molecular Weight ◽  
Mechanical Prophylaxis ◽  
Cord Injury

Study Design: Systematic review. Objectives: The objective of this study was to answer 5 key questions: What is the comparative effectiveness and safety of (1a) anticoagulant thromboprophylaxis compared to no prophylaxis, placebo, or another anticoagulant strategy for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) after acute spinal cord injury (SCI)? (1b) Mechanical prophylaxis strategies alone or in combination with other strategies for preventing DVT and PE after acute SCI? (1c) Prophylactic inferior vena cava filter insertion alone or in combination with other strategies for preventing DVT and PE after acute SCI? (2) What is the optimal timing to initiate and/or discontinue anticoagulant, mechanical, and/or prophylactic inferior vena cava filter following acute SCI? (3) What is the cost-effectiveness of these treatment options? Methods: A systematic literature search was conducted to identify studies published through February 28, 2015. We sought randomized controlled trials evaluating efficacy and safety of antithrombotic strategies. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: Nine studies satisfied inclusion criteria. We found a trend toward lower risk of DVT in patients treated with enoxaparin. There were no significant differences in rates of DVT, PE, bleeding, and mortality between patients treated with different types of low-molecular-weight heparin or between low-molecular-weight heparin and unfractionated heparin. Combined anticoagulant and mechanical prophylaxis initiated within 72 hours of SCI resulted in lower risk of DVT than treatment commenced after 72 hours of injury. Conclusion: Prophylactic treatments can be used to lower the risk of venous thromboembolic events in patients with acute SCI, without significant increase in risk of bleeding and mortality and should be initiated within 72 hours.

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