Comparison of apixaban versus aspirin for the prevention of latent bioprosthetic aortic valve thrombosis: study protocol for a prospective randomized trial.
Humans
Aspirin
/ administration & dosage
Pyridones
/ therapeutic use
Prospective Studies
Heart Valve Prosthesis
/ adverse effects
Bioprosthesis
Aortic Valve
/ surgery
Thrombosis
/ prevention & control
Pyrazoles
/ therapeutic use
Factor Xa Inhibitors
/ administration & dosage
Randomized Controlled Trials as Topic
Heart Valve Prosthesis Implantation
/ adverse effects
Treatment Outcome
Platelet Aggregation Inhibitors
/ administration & dosage
Female
Male
Middle Aged
Time Factors
Aged
Adult
Fibrinolytic Agents
/ administration & dosage
Antithrombotic therapy
Aortic valve replacement
Biological valve
Hypo-attenuated leaflet thickening
Rapid deployment valve
Reduced leaflet motion
Sutureless valve
Valve thrombosis
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
16 May 2024
16 May 2024
Historique:
received:
24
01
2024
accepted:
13
05
2024
medline:
17
5
2024
pubmed:
17
5
2024
entrez:
16
5
2024
Statut:
epublish
Résumé
The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.
Sections du résumé
BACKGROUND
BACKGROUND
The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses.
METHODS
METHODS
In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies.
DISCUSSION
CONCLUSIONS
Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.
Identifiants
pubmed: 38755709
doi: 10.1186/s13063-024-08175-w
pii: 10.1186/s13063-024-08175-w
doi:
Substances chimiques
apixaban
0
Banques de données
ClinicalTrials.gov
['NCT06184113']
Types de publication
Journal Article
Clinical Trial Protocol
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
324Subventions
Organisme : Medicinski Fakultet, Sveučilište u Zagrebu
ID : Grant number 10106-22-3151
Informations de copyright
© 2024. The Author(s).
Références
Aluru JS, Barsouk A, Saginala K, Rawla P, Barsouk A. Valvular heart disease epidemiology. Med Sci (Basel). 2022;10:32. https://doi.org/10.3390/medsci10020032 .
doi: 10.3390/medsci10020032
pubmed: 35736352
Carroll JD, Mack MJ, Vemulapalli S, Herrmann HC, Gleason TG, Hanzel G, et al. STS-ACC TVT registry of transcatheter aortic valve replacement. J Am Coll Cardiol. 2020;76:2492–516. https://doi.org/10.1016/j.jacc.2020.09.595 .
doi: 10.1016/j.jacc.2020.09.595
pubmed: 33213729
Tam DY, Rocha RV, Wijeysundera HC, Austin PC, Dvir D, Fremes SE. Surgical valve selection in the era of transcatheter aortic valve replacement in the Society of Thoracic Surgeons Database. J Thorac Cardiovasc Surg. 2020;159:416-427.e8. https://doi.org/10.1016/j.jtcvs.2019.05.081 .
doi: 10.1016/j.jtcvs.2019.05.081
pubmed: 31350026
Makkar RR, Blanke P, Leipsic J, Thourani V, Chakravarty T, Brown D, et al. Subclinical leaflet thrombosis in transcatheter and surgical bioprosthetic valves. J Am Coll Cardiol. 2020;75:3003–15. https://doi.org/10.1016/j.jacc.2020.04.043 .
doi: 10.1016/j.jacc.2020.04.043
pubmed: 32553252
Makkar RR, Fontana G, Jilaihawi H, Chakravarty T, Kofoed KF, De Backer O, et al. Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N Engl J Med. 2015;373:2015–24. https://doi.org/10.1056/NEJMoa1509233 .
doi: 10.1056/NEJMoa1509233
pubmed: 26436963
De Backer O, Dangas GD, Jilaihawi H, Leipsic JA, Terkelsen CJ, Makkar R, et al. Reduced leaflet motion after transcatheter aortic-valve replacement. N Engl J Med. 2020;382:130–9. https://doi.org/10.1056/NEJMoa1911426 .
doi: 10.1056/NEJMoa1911426
pubmed: 31733182
Blanke P, Leipsic JA, Popma JJ, Yakubov SJ, Deeb GM, Gada H, et al. Bioprosthetic aortic valve leaflet thickening in the Evolut low risk sub-study. J Am Coll Cardiol. 2020;75:2430–42. https://doi.org/10.1016/j.jacc.2020.03.022 .
doi: 10.1016/j.jacc.2020.03.022
pubmed: 32234463
Themudo R, Kastengren M, Bacsovics Brolin E, Cederlund K, Svensson A, Dalén M. Leaflet thickening and stent geometry in sutureless bioprosthetic aortic valves. Heart Vessels. 2020;35:868–75. https://doi.org/10.1007/s00380-020-01553-9 .
doi: 10.1007/s00380-020-01553-9
pubmed: 31950251
Dalén M, Sartipy U, Cederlund K, Franco-Cereceda A, Svensson A, Themudo R, et al. Hypo-attenuated leaflet thickening and reduced leaflet motion in sutureless bioprosthetic aortic valves. J Am Heart Assoc. 2017;6:e005251. https://doi.org/10.1161/JAHA.116.005251 .
doi: 10.1161/JAHA.116.005251
pubmed: 28862959
pmcid: 5586405
Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022;43:561–632. https://doi.org/10.1093/eurheartj/ehab395 .
doi: 10.1093/eurheartj/ehab395
pubmed: 34453165
Christersson C, James SK, Lindhagen L, Ahlsson A, Friberg Ö, Jeppsson A, et al. Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement. Heart. 2020;106:838–44. https://doi.org/10.1136/heartjnl-2019-315453 .
doi: 10.1136/heartjnl-2019-315453
pubmed: 31757813
Rafiq S, Steinbrüchel DA, Lilleør NB, Møller CH, Lund JT, Thiis JJ, et al. Antithrombotic therapy after bioprosthetic aortic valve implantation: warfarin versus aspirin, a randomized controlled trial. Thromb Res. 2017;150:104–10. https://doi.org/10.1016/j.thromres.2016.11.021 .
doi: 10.1016/j.thromres.2016.11.021
pubmed: 27914653
Brennan JM, Edwards FH, Zhao Y, O’Brien S, Booth ME, Dokholyan RS, et al. Early anticoagulation of bioprosthetic aortic valves in older patients: results from the Society of Thoracic Surgeons Adult Cardiac Surgery National Database. J Am Coll Cardiol. 2012;60:971–7. https://doi.org/10.1016/j.jacc.2012.05.029 .
doi: 10.1016/j.jacc.2012.05.029
pubmed: 22921973
Di Eusanio M, Phan K, Berretta P, Carrel TP, Andreas M, Santarpino G, et al. Sutureless and Rapid-Deployment Aortic Valve Replacement International Registry (SURD-IR): early results from 3343 patients†. Eur J Cardiothorac Surg. 2018;54:768–73. https://doi.org/10.1093/ejcts/ezy132 .
doi: 10.1093/ejcts/ezy132
pubmed: 29617925
Vinogradova Y, Coupland C, Hill T, Hippisley-Cox J. Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care. BMJ. 2018;362: k2505. https://doi.org/10.1136/bmj.k2505 .
doi: 10.1136/bmj.k2505
pubmed: 29973392
pmcid: 6031213
Dawwas GK, Leonard CE, Lewis JD, Cuker A. Risk for recurrent venous thromboembolism and bleeding with apixaban compared with rivaroxaban: an analysis of real-world data. Ann Intern Med. 2022;175:20–8. https://doi.org/10.7326/M21-0717 .
doi: 10.7326/M21-0717
pubmed: 34871048
Ingason AB, Hreinsson JP, Ágústsson AS, Lund SH, Rumba E, Pálsson DA, et al. Rivaroxaban is associated with higher rates of gastrointestinal bleeding than other direct oral anticoagulants : a nationwide propensity score-weighted study. Ann Intern Med. 2021;174:1493–502. https://doi.org/10.7326/M21-1474 .
doi: 10.7326/M21-1474
pubmed: 34633836
Généreux P, Piazza N, Alu MC, Nazif T, Hahn RT, Pibarot P, et al. Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research. Eur Heart J. 2021;42:1825–57. https://doi.org/10.1093/eurheartj/ehaa799 .
doi: 10.1093/eurheartj/ehaa799
pubmed: 33871579
Blanke P, Weir-McCall JR, Achenbach S, Delgado V, Hausleiter J, Jilaihawi H, et al. Computed Tomography imaging in the context of transcatheter aortic valve implantation (TAVI)/transcatheter aortic valve replacement (TAVR): an expert consensus document of the society of cardiovascular computed tomography. JACC Cardiovasc Imaging. 2019;12:1–24. https://doi.org/10.1016/j.jcmg.2018.12.003 .
doi: 10.1016/j.jcmg.2018.12.003
pubmed: 30621986
Rashid HN, Rajani R, Leipsic J, Maurovitch-Horvat P, Patterson T, Redwood S, et al. Computed tomography imaging for subclinical leaflet thrombosis following surgical and transcatheter aortic valve replacement. J Cardiovasc Comput Tomogr. 2023;17:2–10. https://doi.org/10.1016/j.jcct.2022.11.001 .
doi: 10.1016/j.jcct.2022.11.001
pubmed: 36396555
Chakravarty T, Søndergaard L, Friedman J, De Backer O, Berman D, Kofoed KF, et al. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. Lancet. 2017;389:2383–92. https://doi.org/10.1016/S0140-6736(17)30757-2 .
doi: 10.1016/S0140-6736(17)30757-2
pubmed: 28330690
Zoghbi WA, Chambers JB, Dumesnil JG, Foster E, Gottdiener JS, Grayburn PA, et al. Recommendations for evaluation of prosthetic valves with echocardiography and Doppler ultrasound. Journal of the American Society of Echocardiography. 2009;22:975–1014. https://doi.org/10.1016/j.echo.2009.07.013 .
doi: 10.1016/j.echo.2009.07.013
pubmed: 19733789
Sondergaard L, De Backer O, Kofoed KF, Jilaihawi H, Fuchs A, Chakravarty T, et al. Natural history of subclinical leaflet thrombosis affecting motion in bioprosthetic aortic valves. Eur Heart J. 2017;38:2201–7. https://doi.org/10.1093/eurheartj/ehx369 .
doi: 10.1093/eurheartj/ehx369
pubmed: 28838044
Cosgrove Iii DM, Sabik JF. Minimally invasive approach for aortic valve operations. Ann Thorac Surg. 1996;62:596–603.
doi: 10.1016/0003-4975(96)00418-3
Martínez-Comendador J, Castaño M, Gualis J, Martín E, Maiorano P, Otero J. Sutureless aortic bioprosthesis. Interact Cardiovasc Thorac Surg. 2017;25:114–21. https://doi.org/10.1093/icvts/ivx051 .
doi: 10.1093/icvts/ivx051
pubmed: 28369578