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Region Hovedstaden - en del af Københavns Universitetshospital
E-pub ahead of print

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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  • Ruben J Eck
  • Wouter Bult
  • Jørn Wetterslev
  • Reinold O B Gans
  • Karina Meijer
  • Frederik Keus
  • Iwan C C van der Horst
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftSeminars in Thrombosis and Hemostasis
ISSN0094-6176
DOI
StatusE-pub ahead of print - 17 okt. 2019

Bibliografisk note

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

ID: 58187201