Pharmacotherapy with rivaroxaban can effectively reduce D-dimer levels in patients with acute coronary syndrome (ACS), according to a study published in The American Journal of Cardiology. The study also found elevated baseline D-dimer levels to have an increased risk for adverse cardiovascular outcomes.
Authors of this post hoc exploratory analysis sought to characterize the safety and efficacy of using rivaroxaban therapy to reduce the influence of D-dimer, a sensitive biomarker of thrombosis, in patients with ACS.
A study sample of 1834 patients enrolled in the ATLAS ACS TIMI-46 trial had baseline D-dimer values available and experienced symptoms suggestive of ACS.
Study participants were randomized to receive rivaroxaban (n=1226) or placebo (n=608), and researchers measured D-dimer levels in a subset of participants before first dose, up to 24 hours after first dose, on day 30, and on day 180.
The efficacy outcome was defined as a composite of cardiovascular events, including cardiovascular death, myocardial infarction, and stroke. Using univariate and multivariable logistic regression models, the authors analyzed the association between baseline D-dimer and 6-month composite clinical outcomes; the change in D-dimer levels from baseline to each time point was compared between treatment groups using the Wilcoxon rank sum test to assess the differences.
In both univariate and multivariable logistic regression analyses, baseline D-dimer levels were associated with increased risk of the composite outcome, reporting an odds ratio of 1.15 (95% CI, 1.03-1.29; P =.015) in univariate analysis and 1.13 (95% CI, 1.00-1.28; P =.048) in multivariable analysis.
Rivaroxaban therapy effectively reduced D-dimer levels compared to placebo after the first study dose was administered (P = .026), at day 30 (P <.001), and at day 180 (P <.001).
The range in sample collection time from the acute coronary syndrome event was not controlled for in the analysis, potentially increasing variability in D-dimer baseline measurements and presenting a limitation of the study. Furthermore, major bleeding was not assessed among study outcomes; the net benefit of rivaroxaban should be estimated against its increased risk of bleeding.
Although higher baseline D-dimer levels were associated with increased risk of cardiovascular death, myocardial infarction, or stroke, the authors conclude that rivaroxaban helped patients with ACS maintain lower D-dimer levels throughout the study course when compared with patients who received placebo.
Multiple authors declare associations with the pharmaceutical industry. Please see original reference for a full list of authors’ disclosures.
AlKhalfan F, Kerneis M, Nafee T, et al. D-dimer levels and effect of rivaroxaban on those levels and outcomes in patients with acute coronary syndrome (an ATLAS ACS-TIMI 46 trial substudy) [published online August 4, 2018]. Am J Cardiol. doi:10.1016/j.amjcard.2018.07.032