SAN DIEGO – Obtaining a baseline D-dimer level can identify acutely ill patients at high risk of venous thromboembolism, results from a large analysis have shown.
In fact, the rate of venous thromboembolism (VTE) was 3.5- to 4-fold higher for patients with a baseline D-dimer level more than twice the upper limit of normal, compared with patients whose D-dimer was twice the upper limit of normal or less, Dr. Alexander T. Cohen reported at the annual meeting of the American Society of Hematology.
Dr. Alexander T. Cohen
The findings come from a subset analysis of patients in MAGELLAN, a trial of 8,101 acutely ill, hospitalized adults who were randomized to either oral rivaroxaban (Xarelto) prophylaxis 10 mg once daily for 35 days or to standard enoxaparin (Lovenox) 40 mg once daily for 10 days, followed by placebo. The patients were assessed with ultrasonography on day 10 and day 35. In the overall study population, rivaroxaban met both of its primary outcomes: noninferiority at day 10 vs. enoxaparin and superiority at day 35 vs. enoxaparin, followed by placebo. Rates of clinically relevant bleeding were low in general but were higher for rivaroxaban than for enoxaparin with placebo. MAGELLAN’s primary findings were presented at the 2011 annual meeting of the American College of Cardiology but have not yet been published.
For the current study, outcomes in MAGELLAN were analyzed to investigate the relationship between D-dimer levels and VTE risk, and the effect of rivaroxaban on this risk. Dr. Cohen of the department of surgery at King’s College Hospital, London, and his associates divided patients into two groups: those with D-dimer levels less than or equal to two times the upper limit of normal or less (group 1) and those with D-dimer levels greater than two times the upper limit of normal (group 2).
The primary efficacy outcome was a composite of asymptomatic proximal deep vein thrombosis (DVT), symptomatic DVT, symptomatic nonfatal pulmonary embolism, and VTE-related death. The principal safety outcomes were major and nonmajor clinically relevant bleeding recorded within 2 days after the last intake of study medication. Both outcomes were assessed on day 10 and day 35, and the prespecified net clinical benefit was defined as a composite of the primary efficacy and principal safety outcomes.
The mean age of the patients was 67 years in group 1 and 71 years in group 2. The baseline median D-dimer level was 0.94 mg/L in all patients. Baseline D-dimer level was higher in patients who experienced a primary efficacy outcome event, compared with those who did not have such an event (a median of 1.98 mg/L vs. 0.92 mg/L). Patients in group 2 were about four times as likely to have a VTE by day 10, compared with those in group 1. At day 10, rivaroxaban was noninferior for the primary efficacy outcome, compared with enoxaparin, among patients in group 2.
At day 35, patients in group 2 who were assigned to the rivaroxaban arm had a reduction in their relative risk of the primary efficacy outcome by 29%, compared with those who were assigned to the enoxaparin-placebo arm, a significant difference that translated into an absolute risk reduction of 2.8% (P = .01). No such differences were observed in group 1.
Patients who had a high D-dimer level at baseline were at increased risk of an event occurring between day 11 and day 35, and rivaroxaban reduced that risk, compared with placebo, during this time period, Dr. Cohen said. "Perhaps assessment of D-dimer after 10 days of standard prophylaxis may indicate which patients benefit from rivaroxaban prophylaxis," he noted.
In both D-dimer groups, the rate of clinically relevant bleeding was significantly higher among patients treated with rivaroxaban, compared with those treated with enoxaparin, followed by placebo, across the entire study period. In the net clinical benefit outcomes analysis, the hazard ratio at day 10 was 1.63 for group 1 and 0.96 for group 2, while the hazard ratio at day 35 was 1.71 for group 1 and 1.03 for group 2.
MAGELLAN was funded by Bayer (which licenses rivaroxaban) and Johnson & Johnson (parent company of Janssen Pharmaceuticals, which manufactures rivaroxaban). Dr. Cohen disclosed that he has served as a medical consultant for, and has received honoraria and clinical trial funding from, numerous pharmaceutical companies, including Bayer, Johnson & Johnson, and Sanofi-Aventis.