High risk of stroke in patients with worsening heart failure, reduced ejection fraction, coronary heart disease and sinus rhythm: Risk prediction score analysis from the COMMANDER-HF trial.

BACKGROUND

Patients with heart failure, reduced ejection fraction (HFrEF) and sinus rhythm have a heightened risk of stroke. Whether anticoagulation benefits these patients is uncertain. In this post-hoc analysis of COMMANDER-HF trial we evaluated how a previously validated risk model consisting of three variables (history of prior stroke, insulin-treated diabetes, and NTproBNP) would perform, compared to plasma D-dimer, for stroke prediction and estimation of the benefit of low-dose rivaroxaban.

METHODS AND RESULTS

Stroke risk and treatment effect were computed across risk score and plasma D-dimer tertiles. Risk score was available in 2,928 (58%) of the COMMANDER-HF population. Over a median follow-up of 512 (342-747) days, 60 patients experienced a stroke (14.6 per 1000 patient-years). The risk model did not identify patients at higher risk of stroke and showed a low overall prognostic performance (C-index=0.53). The effect of rivaroxaban on stroke was homogeneous across risk score tertiles (P-interaction=0.67). Among patients in whom the risk score was estimated, D-dimer was available in 2,343 (80%). D-dimer had an acceptable performance for stroke prediction (C-index=0.66) and higher plasma D-dimer concentrations were associated with higher rates of stroke (i.e. T3 vs. T1, HR 3.65 [95%CI 1.59-8.39], P=0.002). Treatment with low-dose rivaroxaban reduced the incidence of stroke in patients at highest risk by D-dimer levels (i.e. >515 ng/mL; HR 0.42 [95%CI 0.18-0.95], P-interaction=0.074), without any safety concern.

CONCLUSIONS

In our analysis, plasma D-dimer concentrations performed better than a previously described three-variable risk score for stroke prediction in patients with HFrEF, a recent clinical worsening and sinus rhythm as enrolled in the COMMANDER-HF trial. In these patients, a raised plasma D-dimer concentration identified patients who might benefit most from rivaroxaban.

Informations de copyright

Copyright © 2023. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Competing Interest L.M. has received lecture fees from AstraZeneca and Vifor. N.G. has received personal fees from AstraZeneca, Bayer, Boehringer, Lilly, Novartis, Roche Diagnostics, Vifor Pharma. J.P.F. has received consulting fees from Boheringer Ingelheim. S.A. has received grants and personal fees from Abbott Vascular and Vifor; and has received personal fees from Bayer, Boehringer Ingelheim, Brahms GmbH, Cardiac Dimensions, Cordio, Novartis, and Servier. J.G.F.C. has received personal fees from Janssen Research & Development LLC as a member of the steering committee of the COMMANDER HF trial; and has received grants and honoraria for speaking, committees, and advisory boards from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Medtronic, MyoKardia, Novartis, Philips Healthcare, Pharmacosmos, Pharma Nord, Sanofi, Laboratoires Servier, Stealth BioTherapeutics, Torrent Pharmaceuticals, and Vifor Pharma. T.K. has received lecture fees from Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Novartis Pharma K.K., AstraZeneca K.K., Bristol-Myers Squibb Co., Abiomed Japan K.K., and Boehringer Ingelheim. J.J.V.M. has received payments through Glasgow University from work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, DalCor, GSK, Ionis, KBP Biosciences, Novartis, Pfizer, Theracos Personal lecture fees: the Corpus, Abbott, Hikma, Sun Pharmaceuticals, Medscape/Heart.Org, Radcliffe Cardiology, Servier Director, Global Clinical Trial Partners (GCTP). C.S.P.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research & Development LLC, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, Cytokinetics, WebMD Global LLC, Radcliffe Group Ltd and Corpus; and serves as co-founder and non-executive director of eKo.ai. M.R.M. has consulting relationships with Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, NupulseCV, FineHeart, Leviticus, Roivant, Baim Institute for Clinical Research and Triple Gene. D.J.v.V. has received fees for serving on a steering committee and travel support from ARCA biopharma and Corvia Medical. B.G. has received personal fees from Novartis, Janssen, Sanofi, Mesoblast, Zensun, Cellular Dynamics, MyoKardia, Bayer, Actelion, Viking, Amgen, Akcea, EBR System, IONIS, and Tenaya; and was co-chair of the COMMANDER-HF steering committee. F.Z. has received personal fees from Boehringer Ingelheim, Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer, Cellprothera, CVCT and Cardiorenal. All other authors report no disclosures.