Regular Use of VKA Prior to COVID-19 Associated with Lower 7-Day Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Cohort Study

Pierre Ménager, Olivier Brière, Jennifer Gautier, Jérémie Riou, Guillaume Sacco, Antoine Brangier, Cédric Annweiler, On Behalf Of The Geria-Covid Study Group, Pierre Ménager, Olivier Brière, Jennifer Gautier, Jérémie Riou, Guillaume Sacco, Antoine Brangier, Cédric Annweiler, On Behalf Of The Geria-Covid Study Group

Abstract

Background: Vitamin K concentrations are inversely associated with the clinical severity of COVID-19. The objective of this cohort study was to determine whether the regular use of vitamin K antagonist (VKA) prior to COVID-19 was associated with short-term mortality in frail older adults hospitalized for COVID-19.

Methods: Eighty-two patients consecutively hospitalized for COVID-19 in a geriatric acute care unit were included. The association of the regular use of VKA prior to COVID-19 with survival after 7 days of COVID-19 was examined using a propensity-score-weighted Cox proportional-hazards model accounting for age, sex, severe undernutrition, diabetes mellitus, hypertension, prior myocardial infarction, congestive heart failure, prior stroke and/or transient ischemic attack, CHA2DS2-VASc score, HAS-BLED score, and eGFR.

Results: Among 82 patients (mean ± SD age 88.8 ± 4.5 years; 48% women), 73 survived COVID-19 at day 7 while 9 died. There was no between-group difference at baseline, despite a trend for more frequent use of VKA in those who did not survive on day 7 (33.3% versus 8.2%, p = 0.056). While considering "using no VKA" as the reference (hazard ratio (HR) = 1), the HR for 7-day mortality in those regularly using VKA was 5.68 [95% CI: 1.17; 27.53]. Consistently, COVID-19 patients using VKA on a regular basis had shorter survival times than the others (p = 0.031).

Conclusions: Regular use of VKA was associated with increased mortality at day 7 in hospitalized frail elderly patients with COVID-19.

Keywords: COVID-19; SARS-CoV-2; anticoagulation; older adults; survival; vitamin K antagonist.

Conflict of interest statement

C.A. serves as an editorial board member for Nutrients and occasionally serves as a consultant for Bayer France. All authors declare they do not have any other financial and personal conflicts of interest with this manuscript.

Figures

Figure 1
Figure 1
Kaplan–Meier estimates of the cumulative probability of COVID-19 participants’ survival according to the regular use of vitamin K antagonist (VKA) prior to COVID-19 (n = 82).

References

    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X., et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3.
    1. Cui S., Chen S., Li X., Liu S., Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneu-monia. J. Thromb. Haemost. 2020;18:1421–1424. doi: 10.1111/jth.14830.
    1. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost. 2020;18:844–847. doi: 10.1111/jth.14768.
    1. Dofferhoff A.S.M., Piscaer I., Schurgers L.J., Visser M.P.J., Ouweland J.M.W.V.D., A De Jong P., Gosens R., Hackeng T.M., Van Daal H., Lux P., et al. Reduced vitamin K status as a potentially modifiable risk factor of severe COVID-19. Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa1258.
    1. Luo W.-R., Yu H., Gou J.-Z., Li X.-X., Sun Y., Li J.-X., He J.-X., Liu L. Histopatological Findings in the Explant Lungs of a Patient With COVID-19 Treated With Bilateral Orthotopic Lung Transplant. Transplantation. 2020;104:e329–e331. doi: 10.1097/TP.0000000000003412.
    1. Fraser J.D., A Price P. Lung, heart, and kidney express high levels of mRNA for the vitamin K-dependent matrix Gla protein. Implications for the possible functions of matrix Gla protein and for the tissue distribution of the gamma-carboxylase. J. Biol. Chem. 1988;263:11033–11036.
    1. Ansell J., Hirsh J., Hylek E., Jacobson A. Crowther M, Palareti G. American College of Chest Physicians: Pharmacology and Management of the Vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest. 2008;133:160S–198S. doi: 10.1378/chest.08-0670.
    1. French National Security Agency of Medicines and Health Products (ANSM) Anticoagulants in France in 2012: Inventory and Monitoring. [(accessed on 26 November 2020)]; Available online: .
    1. Gąsecka A., Borovac J.A., Guerreiro R.A., Giustozzi M., Parker W.A., Caldeira D., Chiva-Blanch G. Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment. Cardiovasc. Drugs Ther. 2020;2020:1–15. doi: 10.1007/s10557-020-07084-9.
    1. Vetel J.M., Leroux R., Ducoudray J.M. AGGIR. Practical use. Geriatric Autonomy Group Resources Needs. Soins Gérontol. 1998;13:23–27.
    1. Developed with the special contribution of the European Heart Rhythm Association (EHRA) Camm A.J., Kirchhof P., Lip G.Y., Schotten U., Savelieva I., Ernst S., Van Gelder I.C., Al-Attar N., Hindricks G., et al. Guidelines for the management of atrial fibrillation: The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC) Eur. Heart J. 2010;31:2369–2429. doi: 10.1093/eurheartj/ehq278.
    1. Li F., Morgan K.L., Zaslavsky A.M. Balancing Covariates via Propensity Score Weighting. J. Am. Stat. Assoc. 2018;113:390–400. doi: 10.1080/01621459.2016.1260466.
    1. Flaczyk A., Rosovsky R., Reed C.T., Bankhead-Kendall B.K., Bittner E.A., Chang M.G. Comparison of published guidelines for management of coagulopathy and thrombosis in critically ill patients with COVID 19: Implications for clinical practice and future investigations. Crit. Care. 2020;24:1–13. doi: 10.1186/s13054-020-03273-y.
    1. Tremblay D., Van Gerwen M., Alsen M., Thibaud S., Kessler A., Venugopal S., Makki I., Qin Q., Dharmapuri S., Jun T., et al. Impact of anticoagulation prior to COVID-19 infection: A propensity score–matched cohort study. Blood. 2020;136:144–147. doi: 10.1182/blood.2020006941.
    1. Tang N., Bai H., Chen X., Gong J., Li D., Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J. Thromb. Haemost. 2020;18:1094–1099. doi: 10.1111/jth.14817.
    1. Nadkarni G.N., Lala A., Bagiella E., Chang H.L., Moreno P.R., Pujadas E., Arvind V., Bose S., Charney A.W., Chen M.D., et al. Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19. J. Am. Coll. Cardiol. 2020;76:1815–1826. doi: 10.1016/j.jacc.2020.08.041.
    1. Booth S.L., Martini L., Peterson J.W., Saltzman E., Dallal G.E., Wood R.J. Dietary Phylloquinone Depletion and Repletion in Older Women. J. Nutr. 2003;133:2565–2569. doi: 10.1093/jn/133.8.2565.
    1. Nigwekar S.U., Thadhani R., Brandenburg V.M. Calciphylaxis. N. Engl. J. Med. 2018;378:1704–1714. doi: 10.1056/NEJMra1505292.
    1. Chatrou M.L., Winckers K., Hackeng T.M., Reutelingsperger C.P., Schurgers L.J. Vascular calcification: The price to pay for anti-coagulation therapy with vitamin K-antagonists. Blood Rev. 2012;26:155–166. doi: 10.1016/j.blre.2012.03.002.
    1. Price P.A., Buckley J.R., Williamson M.K. The amino bisphosphonate ibandronate prevents vitamin D toxicity and inhibits vita-min D-induced calcification of arteries, cartilage, lungs and kidneys in rats. J. Nutr. 2001;131:2910–2915. doi: 10.1093/jn/131.11.2910.
    1. Rucker R.B. Calcium Binding to Elastin. Adv. Exp. Med. Biol. 1974;48:185–209. doi: 10.1007/978-1-4684-0943-7_10.
    1. Schurgers L.J., Spronk H.M., Soute B.A., Schiffers P.M., DeMey J.G., Vermeer C. Regression of warfarin-induced medial elastocal-cinosis by high intake of vitamin K in rats. Blood. 2007;109:2823–2831. doi: 10.1182/blood-2006-07-035345.
    1. Hardie W.D., Korfhagen T.R., Sartor M.A., Prestridge A., Medvedovic M., Le Cras T.D., Ikegami M., Wesselkamper S.C., Davidson C., Dietsch M., et al. Genomic profile of matrix and vasculature remodeling in TGF-α in-duced pulmonary fibrosis. Am. J. Respir. Cell. Mol. Biol. 2007;37:309–321. doi: 10.1165/rcmb.2006-0455OC.
    1. Booth A.J., Hadley R., Cornett A.M., Dreffs A.A., Matthes S.A., Tsui J.L., Weiss K., Horowitz J.C., Fiore V.F., Barker T.H., et al. Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am. J. Respir. Crit. Care Med. 2012;186:866–876. doi: 10.1164/rccm.201204-0754OC.
    1. Basalyga D.M., Simionescu D.T., Xiong W., Baxter B.T., Starcher B.C., Vyavahare N.R. Elastin degradation and calcification in an abdominal aorta injury model: Role of matrix metalloproteinases. Circulation. 2004;110:3480–3487. doi: 10.1161/01.CIR.0000148367.08413.E9.
    1. Westenfeld R., Krueger T., Schlieper G., Cranenburg E.C., Magdeleyns E.J., Heidenreich S. Effect of vitamin K2 supplemen-tation on functional vitamin K deficiency in hemodialysis patients: A randomized trial. Am. J. Kidney Dis. 2012;59:186–195. doi: 10.1053/j.ajkd.2011.10.041.
    1. Urawa M., Kobayashi T., D’Alessandro-Gabazza C.N., Fujimoto H., Toda M., Roeen Z., A Hinneh J., Yasuma T., Takei Y., Taguchi O., et al. Protein S is protective in pulmonary fibrosis. J. Thromb. Haemost. 2016;14:1588–1599. doi: 10.1111/jth.13362.
    1. Lin C., Von Der Thüsen J., Isermann B., Weiler H., Van Der Poll T., Borensztajn K., Spek C.A. High endogenous activated protein C levels attenuates bleomycin-induced pulmonary fibrosis. J. Cell. Mol. Med. 2016;20:2029–2035. doi: 10.1111/jcmm.12891.
    1. Suleiman L., Negrier C., Boukerche H. Protein S: A multifunctional anticoagulant vitamin K-dependent protein at the cross-roads of coagulation, inflammation, angiogenesis, and cancer. Crit. Rev. Oncol. Hematol. 2013;88:637–654. doi: 10.1016/j.critrevonc.2013.07.004.
    1. Anastasi E., Ialongo C., Labriola R., Ferraguti G., Lucarelli M., Angeloni A. Vitamin K deficiency and covid-19. Scand. J. Clin. Lab. Investig. 2020;80:525–527. doi: 10.1080/00365513.2020.1805122.

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