Plasma <scp>D</scp> ‐dimer concentrations predicting stroke risk and rivaroxaban benefit in patients with heart failure and sinus rhythm: an analysis from the <scp>COMMANDER‐HF</scp> trial
João Pedro Ferreira, Carolyn S.P. Lam, Stefan D. Anker, Mandeep R. Mehra, Dirk J. van Veldhuisen, William M. Byra, David A. La Police, John G.F. Cleland, Barry Greenberg, Faı̈ez Zannad
Abstract
AIMS: D-dimer is a marker of fibrin degradation that reflects intravascular coagulation. Therefore, plasma concentrations of D-dimer might predict thromboembolic risk and rivaroxaban treatment effect. The aims of this study were to investigate the association between D-dimer levels and the risk of stroke and other thrombotic, bleeding and fatal events, and whether D-dimer concentrations could predict rivaroxaban 2.5 mg twice daily (vs. placebo) effect in patients enrolled in the COMMANDER-HF trial who were in sinus rhythm, had heart failure with reduced ejection fraction and coronary artery disease. METHODS AND RESULTS: ) plasma concentration of D-dimer was 360 (215-665) ng/mL. The D-dimer tertiles were: (i) ≤255 ng/mL; (ii) 256-515 ng/mL; and (iii) >515 ng/mL. Patients within the tertile 3 were older, and had lower body mass index, blood pressure, haemoglobin, estimated glomerular filtration rate, and left ventricular ejection fraction. Higher plasma D-dimer concentrations were independently associated with higher rates of death, stroke, and venous thromboembolism. For example, the all-cause death adjusted hazard ratio (HR) (95%CI) of tertile 3 vs. tertile 1 was 1.77 [95% confidence interval (CI) 1.48-2.11; P < 0.001]. The effect of rivaroxaban was similar in each tertile of D-dimer for all outcomes except stroke. Patients within the tertile 3 had the greatest absolute and relative stroke reduction (tertile 1: HR 1.16, 95% CI 0.49-2.74; tertile 2: HR 1.45, 95% CI 0.77-2.73; tertile 3: HR 0.36, 95% CI 0.18-0.70; P for interaction = 0.008). The number-needed-to-treat to prevent one stroke in tertile 3 was 36. CONCLUSIONS: In COMMANDER-HF, rivaroxaban reduced the risk of stroke but the benefit may be confined to patients with D-dimer concentrations above 515 ng/mL. Prospective trials are warranted to confirm these findings.