Plasma D‐dimer concentrations predicting stroke risk and rivaroxaban benefit in patients with heart failure and sinus rhythm: an analysis from the COMMANDER‐HF trial

Ferreira, J. P. , Lam, C. S. P. , Anker, S. D. , Mehra, M. R. , van Veldhuisen, D. J. , Byra, W. M. , La Police, D. A. , Cleland, J. G.F. , Greenberg, B. and Zannad, F. (2020) Plasma D‐dimer concentrations predicting stroke risk and rivaroxaban benefit in patients with heart failure and sinus rhythm: an analysis from the COMMANDER‐HF trial. European Journal of Heart Failure, (doi: 10.1002/ejhf.2003) (Early Online Publication)

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Abstract

Background: D‐dimer is a marker of fibrin degradation that reflects intra‐vascular coagulation. Therefore, plasma concentrations of D‐dimer might predict thromboembolic risk and rivaroxaban treatment effect. Aims: 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 2.5mg/bd (vs. placebo) effect in patients enrolled in the COMMANDER‐HF trial who were in sinus rhythm, had HFrEF and coronary artery disease. Methods: Survival models with treatment‐by‐plasma D‐dimer interaction. Baseline measurement of D‐dimer was available in 4,107 (82%) of 5,022 patients enrolled. Median (percentile25‐75) follow‐up was 21 (12.9‐32.8) months. Results: The median (percentile25‐75) plasma concentration of D‐dimer was 360 (215‐665)ng/mL. The D‐dimer tertiles were: 1) ≤255; 2) 256‐515; 3) >515ng/mL. Patients within the tertile‐3 were older, and had lower BMI, blood pressure, hemoglobin, eGFR, and LVEF. Higher plasma D‐dimer concentrations were independently associated with higher rates of death, stroke, and venous thromboembolism. For example, the all‐cause death adjusted HR (95%CI) of tertile‐3 vs. tertile‐1 was 1.77 (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 (HR [95%CI] tertile‐1=1.16 [0.49‐2.74], tertile‐2=1.45 [0.77‐2.73], and tertile‐3=0.36 [0.18‐0.70]; interactionp=0.008). The number‐needed‐to‐treat to prevent one stroke in tertile‐3 was 36. Conclusion: In COMMANDER‐HF, rivaroxaban reduced the risk of stroke but the benefit may be confined to patients with D‐dimer concentrations above 515ng/mL. Prospective trials are warranted to confirm these findings.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John and Ferreira, Mr Joao Pedro
Authors: Ferreira, J. P., Lam, C. S. P., Anker, S. D., Mehra, M. R., van Veldhuisen, D. J., Byra, W. M., La Police, D. A., Cleland, J. G.F., Greenberg, B., and Zannad, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:European Journal of Heart Failure
Publisher:Wiley
ISSN:1388-9842
ISSN (Online):1879-0844
Published Online:21 September 2020

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