D-dimer as a predictor of venous thromboembolism in acutely ill, hospitalized patients: a subanalysis of the randomized controlled MAGELLAN trial

J Thromb Haemost. 2014 Apr;12(4):479-87. doi: 10.1111/jth.12515.

Abstract

Background: D-dimer concentrations have not been evaluated extensively as a predictor of increased venous thromboembolism (VTE) risk in acutely ill, hospitalized medical patients.

Objectives: To analyze the relationships between D-dimer concentration, VTE and bleeding in the MAGELLAN trial (NCT00571649).

Patients/methods: This was a multicenter, randomized, controlled trial. Patients aged ≥ 40 years, hospitalized for acute medical illnesses with risk factors for VTE received subcutaneous enoxaparin 40 mg once daily for 10 ± 4 days then placebo up to day 35, or oral rivaroxaban 10 mg once daily for 35 ± 4 days. Patients (n = 7581) were grouped by baseline D-dimer ≤ 2 × or > 2 × the upper limit of normal. VTE and major plus non-major clinically relevant bleeding were recorded at day 10, day 35, and between days 11 and 35.

Results: The frequency of VTE was 3.5-fold greater in patients with high D-dimer concentrations. Multivariate analysis showed that D-dimer was an independent predictor of the risk of VTE (odds ratio 2.29 [95% confidence interval 1.75-2.98]), and had a similar association to established risk factors for VTE, for example cancer and advanced age. In the high D-dimer group, rivaroxaban was non-inferior to enoxaparin at day 10 and, unlike the low D-dimer group, superior to placebo at day 35 (P < 0.001) and days 11-35 (P < 0.001). In both groups, bleeding outcomes favored enoxaparin/placebo.

Conclusions: Elevated baseline D-dimer concentrations may identify acutely ill, hospitalized medical patients at high risk of VTE for whom extended anticoagulant prophylaxis may provide greater benefit than for those with low D-dimer concentrations.

Keywords: D-dimer; enoxaparin; hospitalization; rivaroxaban; venous thromboembolism.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Anticoagulants / therapeutic use
  • Enoxaparin / therapeutic use
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Hemorrhage
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Morpholines / therapeutic use*
  • Multivariate Analysis
  • Risk Factors
  • Rivaroxaban
  • Thiophenes / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism / blood*
  • Venous Thromboembolism / diagnosis*

Substances

  • Anticoagulants
  • Enoxaparin
  • Fibrin Fibrinogen Degradation Products
  • Morpholines
  • Thiophenes
  • fibrin fragment D
  • Rivaroxaban

Associated data

  • ClinicalTrials.gov/NCT00571649