Abstract
Background
Sex, age, medical history, treatment, tobacco use, and race (SAMe-TT2R2) score helps detect patients at risk of suboptimal anticoagulation control. A score above two suggests poor control; however, non-Caucasian status being assigned two points might hinder the recognition of poor control in patients of other races.
Objective
To evaluate the SAMe-TT2R2 score’s ability to predict poor anticoagulation control [defined as time in therapeutic range (TTR) < 60–70%] in Asian and non-Asian populations on vitamin K antagonists (VKAs).
Methods
We searched PubMed, Cochrane Library, Scopus, SpringerLink, and Web of Science using the keyword “SAMe-TT2R2.” Articles published before April 2022 were screened. We gathered mean TTR and diagnostic accuracy data for different SAMe-TT2R2 thresholds and conducted meta-analyses using random-effects models.
Results
A total of 30 studies were included (N = 36,690). The overall mean TTR differences were − 4.88 and − 6.41 for the cutoffs of ≥ 3 and ≥ 4, respectively. For non-Asian patients, the mean TTR differences were − 3.86, − 5.12, and − 8.09 for the cutoffs ≥ 2, ≥ 3, and ≥ 4, respectively. For Asian patients, the mean TTR differences were − 3.99 and − 4.07 for the cut-offs ≥ 3 and ≥ 4, respectively. The highest positive likelihood ratio (LR+) for the Asian subgroup was 1.17 [95% confidence interval (CI): 1.06–1.28; I2 = 0%, p heterogeneity = 0.500] at cutoff ≥ 4 and for the non-Asian subgroup, at cut-off ≥ 3, the LR+ was 1.24 (95% CI 1.14–1.34; I2 = 0% p heterogeneity = 0.455). The lowest LR− was found at a lower cutoff for both races (at cutoff ≥ 3 and ≥ 2 for Asian and non-Asian subgroups, respectively). The pooled results of other accuracy parameters were modest at all cutoffs, except for the sensitivity at cutoff ≥ 3 in the Asian subgroup (83.05%).
Conclusion
Our study results suggest that a higher SAMe-TT2R2 score resulted in a greater reduction of TTR among Asian and all races. The accuracy parameters showed the highest sensitivity for poor TTR at the SAMe-TT2R2 cutoff of ≥ 3 for Asian patients. However, the ability to identify patients likely to have poor TTR was limited. Further research is needed to enhance the risk assessment for poor anticoagulation control with VKAs.
Registration
The protocol of this systematic review was registered in the International Prospective Register of Scientific Reviews: PROSPERO, registration number CRD42021291865.
Graphical Abstract
Similar content being viewed by others
References
Lippi G, Sanchis-Gomar F, Cervellin G. Global epidemiology of atrial fibrillation: an increasing epidemic and public health challenge. Int J Stroke. 2021;16(2):217–21. https://doi.org/10.1177/1747493019897870.
Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373–498. https://doi.org/10.1093/eurheartj/ehaa612.
Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest. 2021;160(6):e545–608. https://doi.org/10.1016/j.chest.2021.07.055.
Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2):e152S – e184.
Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology foundation guide to warfarin therapy. J Ame College Cardiol. 2003;41(9):1633–52.
Rosendaal F, Cannegieter S, Van der Meer F, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993;69(03):236–9.
Haas S, Ten Cate H, Accetta G, et al. Quality of vitamin K antagonist control and 1-year outcomes in patients with atrial fibrillation: a global perspective from the GARFIELD-AF registry. PLoS ONE. 2016;11(10): e0164076.
Senoo K, Lau YC, Lip GY. Updated NICE guideline: management of atrial fibrillation (2014). Milton Park: Taylor & Francis; 2014. p. 1037–40.
Ogawa S, Aonuma K, Tse H-F, et al. The APHRS’s 2013 statement on antithrombotic therapy of patients with nonvalvular atrial fibrillation. J Arrhythm. 2013;29(3):190–200. https://doi.org/10.1016/j.joa.2013.03.002.
Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Kardiol Pol. 2016;74(12):1359–469.
Chiang C-E, Okumura K, Zhang S, et al. 2017 consensus of the Asia Pacific Heart Rhythm Society on stroke prevention in atrial fibrillation. J Arrhythm. 2017;33(4):345–67. https://doi.org/10.1016/j.joa.2017.05.004.
Apostolakis S, Sullivan RM, Olshansky B, Lip GY. Factors affecting quality of anticoagulation control among patients with atrial fibrillation on warfarin: the SAMe-TT2R2 score. Chest. 2013;144(5):1555–63. https://doi.org/10.1378/chest.13-0054.
Limdi NA, Brown TM, Yan Q, et al. Race influences warfarin dose changes associated with genetic factors. Blood. 2015;126(4):539–45.
Shen AY-J, Yao JF, Brar SS, et al. Racial/ethnic differences in ischemic stroke rates and the efficacy of warfarin among patients with atrial fibrillation. Stroke. 2008;39(10):2736–43.
Rieder MJ, Reiner AP, Gage BF, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. New Engl J Med. 2005;352(22):2285–93.
Chiang CE, Wang KL, Lip GY. Stroke prevention in atrial fibrillation: an Asian perspective. Thromb Haemost. 2014;111(5):789–97. https://doi.org/10.1160/th13-11-0948.
Romiti GF, Corica B, Proietti M, et al. Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry. EClinicalMedicine. 2023;63: 102039. https://doi.org/10.1016/j.eclinm.2023.102039.
van Miert JH, Bos S, Veeger NJ, Meijer K. Clinical usefulness of the SAMe-TT2R2 score: a systematic review and simulation meta-analysis. PLoS ONE. 2018;13(3): e0194208. https://doi.org/10.1371/journal.pone.0194208.
Krittayaphong R, Winijkul A, Pirapatdit A, et al. SAMe-TT2R2 score for prediction of suboptimal time in therapeutic range in a Thai population with atrial fibrillation. Singapore Med J. 2020;61(12):641–6. https://doi.org/10.11622/smedj.2019143.
Fauchier L, Angoulvant D, Lip GY. The SAMe-TT2R2 score and quality of anticoagulation in atrial fibrillation: a simple aid to decision-making on who is suitable (or not) for vitamin K antagonists. Europace. 2015;17(5):671–3. https://doi.org/10.1093/europace/euv088.
Roldán V, Cancio S, Gálvez J, et al. The SAMe-TT2R2 score predicts poor anticoagulation control in AF patients: a prospective “real-world” inception cohort study. Am J Med. 2015;128(11):1237–43. https://doi.org/10.1016/j.amjmed.2015.05.036.
Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529–36.
Shor E, Roelfs D, Vang ZM. The “Hispanic mortality paradox” revisited: Meta-analysis and meta-regression of life-course differentials in Latin American and Caribbean immigrants’ mortality. Soc Sci Med. 2017;186:20–33. https://doi.org/10.1016/j.socscimed.2017.05.049.
Schünemann HJ, Vist GE, Higgins JP et al. Interpreting results and drawing conclusions. Cochrane handbook for systematic reviews of interventions. 2019:403–31.
Schünemann HJ, Oxman AD, Brozek J, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336(7653):1106–10. https://doi.org/10.1136/bmj.39500.677199.AE.
Park YK, Lee MJ, Kim JH, et al. Lack of association of clinical factors (SAMe-TT2R2) with CYP2C9/VKORC1 genotype and anticoagulation control quality. J Stroke. 2015;17(2):192–8. https://doi.org/10.5853/jos.2015.17.2.192.
Chan PH, Hai JJ, Chan EW, et al. Use of the SAMe-TT2R2 score to predict good anticoagulation control with warfarin in Chinese patients with atrial fibrillation: relationship to ischemic stroke incidence. PLoS ONE. 2016;11(3): e0150674. https://doi.org/10.1371/journal.pone.0150674.
Bernaitis N, Ching CK, Chen LP, et al. The sex, age, medical history, treatment, tobacco use, race risk (SAMe TT2R2) score predicts warfarin control in a Singaporean population. J Stroke Cerebrovasc Dis. 2017;26(1):64–9. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.08.030.
Leedumrongwattanakul A. SAMe-TT2R2 score for prediction of anticoagulation control in Thai patients with non-valvular atrial fibrillation. J Med Assoc Thailand. 2021. https://doi.org/10.35755/jmedassocthai.2021.06.12415.
Lertsanguansinchai P, Huntrakul A, Rungpradubvong V, Chokesuwattanaskul R, Prechawat S. Factors predicting poor anticoagulant control on warfarin in a Thai population with non-valvular atrial fibrillation (NVAF): the ACAChE score. Int J Arrhythm. 2021;22(1):1–11.
Li Y, Yu J, Kuang Y, et al. Quality of oral anticoagulation control in Chinese patients with non-valvular atrial fibrillation: a prospective controlled study. Curr Med Res Opin. 2020;36(9):1433–9. https://doi.org/10.1080/03007995.2020.1796611.
Methavigul K. Proportion of Thai patients with atrial fibrillation receiving warfarin with labile inr in each group of SAMeTT2R2 score. J Med Assoc Thailand. 2018;101(2):189–93.
Methavigul K. Use of SAMe-TT2R2 score to predict the quality of anticoagulation control in patients with atrial fibrillation receiving warfarin in Thailand. J Med Assoc Thailand. 2020;103(6):548–52. https://doi.org/10.35755/jmedassocthai.2020.06.10827.
Liu J, Wang N, Qin L, et al. Integrating genotypes in the SAMe-TT2R2 score for the prediction of anticoagulation control in Chinese patients with atrial fibrillation on warfarin. Int J Cardiol. 2017;241:358–63. https://doi.org/10.1016/j.ijcard.2017.04.092.
Abumuaileq RR, Abu-Assi E, Raposeiras-Roubin S, et al. Evaluation of SAMe-TT2R2 risk score for predicting the quality of anticoagulation control in a real-world cohort of patients with non-valvular atrial fibrillation on vitamin-K antagonists. Europace. 2015;17(5):711–7. https://doi.org/10.1093/europace/euu353.
Gallego P, Roldán V, Marin F, et al. SAMe-TT2R2 score, time in therapeutic range, and outcomes in anticoagulated patients with atrial fibrillation. Am J Med. 2014;127(11):1083–8. https://doi.org/10.1016/j.amjmed.2014.05.023.
Poli D, Antonucci E, Testa S, Lip GY. A prospective validation of the SAME-TT2R 2 score: how to identify atrial fibrillation patients who will have good anticoagulation control on warfarin. Intern Emerg Med. 2014;9(4):443–7. https://doi.org/10.1007/s11739-014-1065-8.
Ruiz-Ortiz M, Bertomeu V, Cequier Á, Marín F, Anguita M. Validation of the SAMe-TT2R2 score in a nationwide population of nonvalvular atrial fibrillation patients on vitamin K antagonists. Thromb Haemost. 2015;114(4):695–701. https://doi.org/10.1160/th15-02-0169.
Lobos-Bejarano JM, Castellanos Rodríguez A, Barrios V, et al. Influence of renal function on anticoagulation control in patients with non-valvular atrial fibrillation taking vitamin K antagonists. Int J Clin Pract. 2017. https://doi.org/10.1111/ijcp.12974.
Palareti G, Antonucci E, Lip GY, et al. The SAME-TT2R2 score predicts the quality of anticoagulation control in patients with acute VTE. A real-life inception cohort study. Thromb Haemost. 2016;115(6):1101–8. https://doi.org/10.1160/th15-10-0830.
Proietti M, Lane DA, Lip GY. Relation of the SAMe-TT2R2 score to quality of anticoagulation control and thromboembolic events in atrial fibrillation patients: observations from the SPORTIF trials. Int J Cardiol. 2016;216:168–72. https://doi.org/10.1016/j.ijcard.2016.04.131.
Bryk AH, Plens K, Undas A. Prediction of unstable anticoagulation with acenocoumarol versus warfarin in atrial fibrillation. Cardiol J. 2017;24(5):477–83. https://doi.org/10.5603/CJ.a2017.0038.
Demelo-Rodríguez P, Postigo-Esteban A, García-Fernández-Bravo I, et al. Evaluation of the SAMe-TT2R2 score to predict the quality of anticoagulation control in a cohort of patients with venous thromboembolism treated with vitamin K antagonists. Thromb Res. 2016;147:58–60. https://doi.org/10.1016/j.thromres.2016.09.021.
Kataruka A, Kong X, Haymart B, et al. SAMe-TT2R2 predicts quality of anticoagulation in patients with acute venous thromboembolism: the MAQI2 experience. Vasc Med. 2017;22(3):197–203. https://doi.org/10.1177/1358863X16682863.
Pivatto F, Scheffel RS, Ries L, et al. SAMe-TT 2 R 2 score in the outpatient anticoagulation clinic to predict time in therapeutic range and adverse events. Arq Bras Cardiol. 2017;108:290–6. https://doi.org/10.5935/abc.20170052.
Szymanski FM, Lip GY, Filipiak KJ, Platek AE, Karpinski G. Usefulness of the SAME-TT2R2 score to predict anticoagulation control on VKA in patients with atrial fibrillation and obstructive sleep apnea. Int J Cardiol. 2016;204:200–5. https://doi.org/10.1016/j.ijcard.2015.11.158.
Barco S, Granziera S, Coppens M, et al. Determinants of the quality of warfarin control after venous thromboembolism and validation of the SAMe-TT2-R2 score: an analysis of Hokusai-VTE. Thromb Haemost. 2019;119(04):675–84. https://doi.org/10.1055/s-0039-1678546.
Esteve-Pastor MA, Rivera-Caravaca JM, Roldán-Rabadán I, et al. Quality of oral anticoagulation with vitamin K antagonists in “real-world” patients with atrial fibrillation: a report from the prospective multicentre FANTASIIA registry. Europace. 2018;20(9):1435–41. https://doi.org/10.1093/europace/eux314.
Mora-Llabata V, Dubois-Marqués D, Moreno-Prat M, et al. Utilidad marginal de la escala SAMe-TT2R2 en la predicción de la calidad de la anticoagulación oral con acenocumarol en el “mundo real.” Rev Colomb Cardiol. 2018;25(3):185–91. https://doi.org/10.1016/j.rccar.2017.10.004.
Bernaitis N, Badrick T, Anoopkumar-Dukie S. The SAMe–TT2R2 score as an indicator of warfarin control for patients with deep vein thrombosis in Queensland, Australia. J Thromb Thrombol. 2020;50(3):614–8. https://doi.org/10.1007/s11239-020-02068-w.
Bernaitis N, Clark G, Kohja S, Leong S, Anoopkumar-Dukie S. The SAMe-TT(2)R(2) score predicts warfarin control in an australian population with atrial fibrillation. J Clin Med. 2019. https://doi.org/10.3390/jcm8060882.
Del-Toro-Cervera J, Demelo-Rodriguez P, Galeano-Valle F, et al. Evaluation of the SAMe-TT2R2 score to predict the quality of anticoagulation control in patients with venous thromboembolism treated with vitamin K antagonists: Findings from the RIETE registry. Thromb Res. 2020;194:178–82. https://doi.org/10.1016/j.thromres.2020.06.022.
Wang K, Lu Y, Simegn MA, Xue H, Asinger RW. Use of SAMe-TT2R2 in a racially diverse anticoagulation clinic: prediction of optimal anticoagulation. J Thromb Thrombolysis. 2022;55:1–6.
Klok FA, Hösel V, Clemens A, et al. Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment. Eur Respir J. 2016;48(5):1369–76. https://doi.org/10.1183/13993003.00280-2016.
Incomenoy S, Saokaew S, Poonchuay N. SAMe-TT2R2 to predict clinical outcomes and time in therapeutic range in patients on vitamin K antagonists: a systematic review and meta-analysis. Ann Pharmacother. 2023. https://doi.org/10.1177/10600280231166643.
Golwala H, Jackson LR 2nd, Simon DN, et al. Racial/ethnic differences in atrial fibrillation symptoms, treatment patterns, and outcomes: insights from Outcomes Registry for Better Informed Treatment for Atrial Fibrillation Registry. Am Heart J. 2016;174:29–36. https://doi.org/10.1016/j.ahj.2015.10.028.
Zawawi NA, Abdul Halim Zaki I, Ming LC, Goh HP, Zulkifly HH. Anticoagulation control in different ethnic groups receiving vitamin K antagonist for stroke prevention in atrial fibrillation. Front Cardiovasc Med. 2021;8:736143. https://doi.org/10.3389/fcvm.2021.736143.
Ambe K, Akita A, Wei J, et al. Comparison of efficacy and safety of direct oral anticoagulants and warfarin between patients in Asian and non-Asian regions: a systematic review and meta-regression analysis. Clin Pharmacol Ther. 2023. https://doi.org/10.1002/cpt.2881.
Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010;376(9745):975–83. https://doi.org/10.1016/s0140-6736(10)61194-4.
Al-Eitan LN, Almasri AY, Khasawneh RH. Effects of CYP2C9 and VKORC1 polymorphisms on warfarin sensitivity and responsiveness during the stabilization phase of therapy. Saudi Pharm J. 2019;27(4):484–90. https://doi.org/10.1016/j.jsps.2019.01.011.
Williams BA, Evans MA, Honushefsky AM, Berger PB. Clinical prediction model for time in therapeutic range while on warfarin in newly diagnosed atrial fibrillation. J Am Heart Assoc. 2017;6(10): e006669. https://doi.org/10.1161/JAHA.117.006669.
Lin KJ, Singer DE, Glynn RJ, et al. Prediction score for anticoagulation control quality among older adults. J Am Heart Assoc. 2017. https://doi.org/10.1161/jaha.117.006814.
Methavigul K, Yindeengam A, Krittayaphong R. Efficacy and safety outcomes of patients with atrial fibrillation compared between warfarin and non-vitamin K antagonist oral anticoagulants based on SAMe-TT2R2 score. BMC Cardiovasc Disord. 2023;23(1):43. https://doi.org/10.1186/s12872-023-03053-w.
Acknowledgements
This study was greatly supported by the Drug and Cosmetics Excellence Center and the School of Pharmacy, Walailak University, the Center of Health Outcomes Research and Therapeutic Safety (Cohorts), and the Unit of Excellence On Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao. We would also like to thank Editage (http://www.editage.com) for English language editing.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
No external funding was used in the preparation of this manuscript.
Conflict of interest
Natnicha Poonchuay, Surasak Saokaew, and Supatcha Incomenoy declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.
Author contributions
All authors contributed to the study conception and design, acquisition, analysis, interpretation, and statistical analysis of data, writing, and critical revision of the manuscript. Poonchuay and Incomenoy had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.
Data availability statement
All data generated or analyzed during this study are included in this published article and its supplementary information files.
Ethics approval and consent to participate
Approval for this study was obtained from the Human Research Ethics Committee of Walailak University, identified by registration number WUEC-21-329-01 and WUEC-21-329-02 (extension of approval). Consent to participate was not required.
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Code availability
Not applicable.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Poonchuay, N., Saokaew, S. & Incomenoy, S. SAMe-TT2R2 Score to Predict Time in Therapeutic Range of Vitamin K Antagonists in Asian and Non-Asian patients: A Systematic Review and Meta-analysis. Am J Cardiovasc Drugs 24, 211–240 (2024). https://doi.org/10.1007/s40256-023-00623-3
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40256-023-00623-3