Plasmad-Dimer Concentrations Predicting Stroke Risk And Rivaroxaban Benefit In Patients With Heart Failure And Sinus Rhythm: An Analysis From Thecommander-Hftrial

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 Survival models with treatment-by-plasma D-dimer interaction. Baseline measurement of D-dimer was available in 4107 (82%) of 5022 patients enrolled. Median (percentile(25-75)) follow-up was 21 (12.9-32.8) months. The median (percentile(25-75)) 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;Pfor 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.