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

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Eck, Ruben J ; Bult, Wouter ; Wetterslev, Jørn ; Gans, Reinold O B ; Meijer, Karina ; Keus, Frederik ; van der Horst, Iwan C C. / Intermediate Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis : Systematic Review with Meta-Analysis and Trial Sequential Analysis. In: Seminars in Thrombosis and Hemostasis. 2019 ; Vol. 45, No. 8. pp. 810-824.

Bibtex

@article{348a7175731341169573f3c2a8416654,
title = "Intermediate Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis",
abstract = "Different 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.",
keywords = "LMWH, low-molecular-weight heparin, meta-analysis, systematic review, thrombosis",
author = "Eck, {Ruben J} and Wouter Bult and J{\o}rn Wetterslev and Gans, {Reinold O B} and Karina Meijer and Frederik Keus and {van der Horst}, {Iwan C C}",
note = "Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.",
year = "2019",
doi = "10.1055/s-0039-1696965",
language = "English",
volume = "45",
pages = "810--824",
journal = "Seminars in Thrombosis and Hemostasis",
issn = "0094-6176",
publisher = "Thieme Medical Publishers",
number = "8",

}

RIS

TY - JOUR

T1 - Intermediate Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis

T2 - Systematic Review with Meta-Analysis and Trial Sequential Analysis

AU - Eck, Ruben J

AU - Bult, Wouter

AU - Wetterslev, Jørn

AU - Gans, Reinold O B

AU - Meijer, Karina

AU - Keus, Frederik

AU - van der Horst, Iwan C C

N1 - Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

PY - 2019

Y1 - 2019

N2 - Different 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.

AB - Different 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.

KW - LMWH

KW - low-molecular-weight heparin

KW - meta-analysis

KW - systematic review

KW - thrombosis

UR - http://www.scopus.com/inward/record.url?scp=85074445610&partnerID=8YFLogxK

U2 - 10.1055/s-0039-1696965

DO - 10.1055/s-0039-1696965

M3 - Journal article

C2 - 31622991

VL - 45

SP - 810

EP - 824

JO - Seminars in Thrombosis and Hemostasis

JF - Seminars in Thrombosis and Hemostasis

SN - 0094-6176

IS - 8

ER -

ID: 58187201