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Original Research: Antithrombotic Therapy |

Relationship of the SAMe-TT2R2 Score to Poor-Quality Anticoagulation, Stroke, Clinically Relevant Bleeding, and Mortality in Patients With Atrial Fibrillation-TT2R2 Score in Atrial Fibrillation FREE TO VIEW

Gregory Y. H. Lip, MD; Ken Haguenoer, MD; Christophe Saint-Etienne, MD; Laurent Fauchier, MD, PhD
Author and Funding Information

From the University of Birmingham Centre for Cardiovascular Sciences (Dr Lip), City Hospital, Birmingham, England; and Service de Cardiologie (Drs Haguenoer, Saint-Etienne, and Fauchier), Pôle Coeur Thorax Vasculaire, Centre Hospitalier, Universitaire Trousseau et Faculté de Médecine, Université François Rabelais, Tours, France.

CORRESPONDENCE TO: Gregory Y. H. Lip, MD, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, England; e-mail: g.y.h.lip@bham.ac.uk


FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(3):719-726. doi:10.1378/chest.13-2976
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BACKGROUND:  The efficacy and safety of anticoagulation with use of vitamin K antagonists (VKAs) is highly dependent on the quality of anticoagulation control as reflected by the average time in a therapeutic range of 2.0 to 3.0. A clinical dilemma is trying to predict which anticoagulation-naive patients with atrial fibrillation (AF) would do well on a VKA (with a time in therapeutic range > 70%) and which are less likely to do well on a VKA but could be managed with novel oral anticoagulants.

METHODS:  The cohort comprised 8,120 patients, among whom 4,637 patients were receiving VKA. We investigated whether the SAMe-TT2R2 (sex female, age < 60 years, medical history [more than two comorbidities], treatment [interacting drugs, eg, amiodarone for rhythm control], tobacco use [doubled], race [doubled]) score could discriminate among patients with AF who were likely to have a labile international normalized ratio (INR) during follow-up as well as stroke/thromboembolism (TE), clinically relevant bleeding (defined as severe bleeding and as Bleeding Academic Research Consortium [BARC]-defined major bleeding), and death while being treated with a VKA.

RESULTS:  During a mean follow-up of 1,016 ± 1,108 days, there was a significant increase in risk of severe bleeding events (risk ratio [RR], 1.38; 95% CI, 1.12-2.68; P = .002) and a significant increase in risk of major BARC bleeding (RR, 1.77; 95% CI, 1.29-2.44; P = .0005) in patients with AF with a high SAMe-TT2R2 score (> 2). Increasing SAMe-TT2R2 score was associated with an increasing risk of labile INR (P = .004), stroke/TE (P = .007), severe bleeding (P < .0001), major BARC bleeding (P < .0001), and death (P = .002) at follow-up. Among the patients taking VKAs, the SAMe-TT2R2 score was predictive of labile INR (C statistic approximately 0.58) as well as of stroke/TE, severe bleeding, major BARC bleeding, and death (C statistic, 0.54-0.57 for events), reflecting the suboptimal time in therapeutic range in such patients. This was not the case for patients who were not taking VKAs.

CONCLUSIONS:  We demonstrate that the SAMe-TT2R2 score was predictive for an increasing risk of stroke/TE, severe bleeding, major BARC bleeding, and death, reflecting poor anticoagulation control (and labile INRs) among patients with AF given VKAs.

Figures in this Article

Patients with atrial fibrillation (AF) are at high risk for stroke/thromboembolism (TE) and death, which are significantly reduced by oral anticoagulation (OAC) therapy. Use of OAC confers an increased risk of bleeding, but the efficacy and safety of anticoagulation with vitamin K antagonists (VKAs) is highly dependent on the quality of anticoagulation control, as reflected by the average time in a therapeutic range of 2.0 to 3.0.1,2 Numerous studies have shown that the rates of stroke/TE and major bleeding are lowest at high average individual times in therapeutic range (TTRs), and recent European consensus recommends that when VKAs are used, the optimal average TTR is > 70%.3,4

Recently, the availability of non-VKA OACs (previously called new or novel OACs) has changed the landscape of stroke prevention in AF.5 A clinical dilemma is trying to decide upfront which anticoagulation-naive patients would do well on a VKA (with a TTR > 70%) and which of those would do less well on a VKA but could be managed with a novel OAC.

Apostolakis et al6 proposed using the SAMe-TT2R2 (sex female, age < 60 years, medical history [more than two comorbidities], treatment [interacting drugs, eg, amiodarone for rhythm control], tobacco use [doubled], race [doubled]) score, which helps to predict which patients would do well on a VKA with a TTR > 70% (SAMe-TT2R2 score, 0-1) and which would do less well (SAMe-TT2R2 score, ≥ 2). The SAMe-TT2R2 score was derived from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial population and performed well in both internal and external validation cohorts. Nonetheless, the SAMe-TT2R2 score requires additional external validation in independent cohorts and, importantly, to assess whether the predictive value of the SAMe-TT2R2 score for TTR would translate to a difference in efficacy and safety end points related to patients with AF treated with VKAs.

We tested the hypothesis that the SAMe-TT2R2 score could discriminate patients with AF who were likely to have a labile international normalized ratio (INR) during follow-up and that this would lead to stroke/TE, clinically relevant bleeding (defined as severe bleeding and Bleeding Academic Research Consortium [BARC]-defined major bleeding), and death while being treated with a VKA, reflecting the poor TTR evident among these patients. The objective was not to use the SAMe-TT2R2 score as a risk predictor for stroke or bleeding per se, given the availability of simple, well-validated scores for this purpose, but to test the clinical utility of using the SAMe-TT2R2 score to reflect subsequent poor anticoagulation control (ie, labile INRs) among patients with AF treated with VKA and the adverse events (TE, bleeding) associated with poor TTRs.

The methods of the Loire Valley Atrial Fibrillation Project, a hospital-based registry of AF in a defined geographic area of Tours, France, have been previously reported.7 In brief, at the Centre Hospitalier Régional et Universitaire in Tours, all patients given a diagnosis of nonvalvular AF or atrial flutter by the Department of Cardiology between 2000 and 2010 were identified (Fig 1). The institution includes a total of four hospitals covering all medical and surgical specialties and is, to our knowledge,the only public institution in an area of around 4,000 km2 and serves approximately 400,000 inhabitants. Patients with nonvalvular AF comprised those directly admitted to the inpatient cardiology service and those seen as a consultation in any service and subsequently proposed for cardiology service admission. Patients were followed from the first record of nonvalvular AF after January 1, 2000 (ie, index date), up to the latest data collection. Treatment at discharge was obtained by screening hospitalization reports, and information on comorbidities was obtained from the computerized coding system. In this comprehensive analysis, we did not exclude periods of initiation and intentional lowering (eg, for an interventional procedure or an operation) of any antithrombotic therapy for any patient.

Figure Jump LinkFigure 1  Study population. SAMETT2R2 = sex female, age < 60 y, medical history (more than two comorbidities), treatment (interacting drugs, eg, amiodarone for rhythm control), tobacco use (doubled), race (doubled); VKA = vitamin K antagonist.Grahic Jump Location

The CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke or transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) scores were calculated following the first diagnosis of AF during hospital admission as a measure of stroke risk,8,9 as was the HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly [> 65 years], drugs/alcohol concomitantly) score as a measure of bleeding risk.10 During follow-up, information on outcomes of TE, stroke (ischemic or hemorrhagic), major bleeding, and all-cause mortality were recorded by active surveillance of hospital administrative data.

For each patient, the SAMe-TT2R2 score was calculated as the sum of points after addition of one point each for female sex, age < 60 years, medical history of more than two comorbidities (among hypertension, diabetes, coronary artery disease/myocardial infarction, peripheral arterial disease, congestive heart failure, previous stroke, pulmonary disease, and hepatic or renal disease), treatment (interacting drugs, eg, amiodarone for rhythm control), and two points each for tobacco use and non-white race. Because recording of race is not allowed in any electronic file in France, the last item was actually not included, but the local population was essentially white. Patients with an SAMe-TT2R2 score of 0 to 1 were deemed to have a low risk, 2 as an intermediate/moderate risk, and > 2 as a high risk for not doing well on a VKA.

Severe bleeding was defined as a decrease in blood hemoglobin level of > 5.0 g/dL (including the period around the coronary interventional procedure), the need for transfusion of one or more units of blood, the need for corrective surgery, the occurrence of an intracranial or retroperitoneal hemorrhage, or any combination of these events. Major bleeding was defined using the BARC bleeding definitions: intracranial hemorrhage, intraocular bleeding compromising vision, overt bleeding plus hemoglobin drop > 5 g/dL, tamponade, bleeding requiring surgical or percutaneous intervention for control (excluding dental, nose, skin, hemorrhoids) or inotropes (BARC type 3A), any transfusion with overt bleeding, overt bleeding plus a hemoglobin drop of 3 to 5 g/dL (BARC type 3B), or fatal bleeding. All information on serious bleeding was identified, with the diagnosis coded in a subsequent hospitalization during follow-up.

Labile INR was defined as that recorded by the responsible clinician in the medical records and the discharge letter among patients receiving VKAs. As with many real-world registries, we did not have actual INRs to calculate TTRs and fully recognize this limitation in this dataset. Nonetheless, a physician-defined labile INR diagnosis is probably a very conservative definition because this would be based on clinical review of INRs as well as on efforts to try and improve TTR before giving a patient such a diagnostic label. The study was approved by the Review Board of the Pole Coeur Thorax Vaisseaux from the Trousseau University Hospital (December 7, 2010).

Statistical Analysis

Patient characteristics are presented as percentages and mean ± SD. χ2 Tests were used to compare categorical variables between the two groups, and the Student t test or the nonparametric Kruskal-Wallis test, where appropriate, were used to compare continuous variables. A Cox model was used to identify independent characteristics associated with the occurrence of an event during follow-up. Potential confounding factors were entered into the model for adjustment. The results are expressed as hazard ratios and 95% CIs.

We calculated the Harrell C statistic with 95% CIs as a measure of the risk prediction abilities of SAMe-TT2R2 for the various end points. C statistics measure how well the risk prediction scheme identifies patients who will have a future event. For estimating C statistics, we analyzed SAMe-TT2R2 scores as risk scores (0-9) and as risk groups (low, intermediate, high). We constructed survival curves based on Kaplan-Meier estimates of the probability of remaining free of events with a score of 0 and 1 for the two risk stratification schemes. P < .05 was considered statistically significant. We used SAS version 9.1 (SAS Institute Inc), StatView version 5.0 (SAS Institute Inc), and MedCalc version 9.3 (MedCalc Software) statistical software for the analyses.

The cohort comprised 8,120 patients, among whom 4,637 patients (57%) were taking VKAs during follow-up (Fig 1). Patient characteristics are shown in Table 1. Among patients receiving anticoagulation therapy, there was a lower prevalence of women and coronary artery disease (and prior myocardial infarction) and more heart failure, hypertension, stroke, diabetes, COPD, and permanent AF. Mean age and CHADS2, CHA2DS2-VASc, and HAS-BLED scores were similar between patients taking VKAs and patients not taking VKAs.

Table Graphic Jump Location
TABLE 1  ] Characteristics of the Patients With Atrial Fibrillation

Data are presented as mean ± SD or No. (%). ACE = angiotensin-converting enzyme; AT2 = angiotensin II; CHADS2 = congestive heart failure, hypertension, age ≥ 75 y, diabetes, prior stroke or transient ischemic attack; CHA2DS2-VAS = congestive heart failure, hypertension, age ≥ 75 y, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65 to 74 y, and sex category; ESC = European Society of Cardiology; HAS-BLED = hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 y), drugs/alcohol concomitantly; ICD = implantable cardioverter defibrillator; LVEF = left ventricular ejection fraction; OAC = oral anticoagulation.

The proportions of patients with labile INR, stroke/TE, and clinically relevant bleeding and who died by category of SAMe-TT2R2 score are shown in Table 2. As shown in Table 2, 172 patients had labile INR, whereas 139 had labile INR while treated with VKAs (Table 3). With increasing SAMe-TT2R2 score, there was an increased risk (with higher HRs) of labile INR (P = .004), stroke/TE (P = .007), severe bleeding (P < .0001), major BARC bleeding (P < .0001), and death (P = .002) at follow-up. During a mean follow-up of 1,016 ± 1,108 days in patients treated with VKAs, 139 patients had labile INRs, whereas stroke/TE developed in 379, severe bleeding developed in 480 (of whom 144 were classified as having major BARC bleeding), and 497 died.

Table Graphic Jump Location
TABLE 2  ] Labile INR, Stroke/TE, Clinically Relevant Bleeding, and Mortality by Category of SAMe-TT2R2 Score

Data are presented as No. (%) or hazard ratio (95% CI). BARC = Bleeding Academic Research Consortium; INR = international normalized ratio; Ref = reference; SAMe-TT2R2 = sex female, age < 60 y, medical history (more than two comorbidities), treatment (interacting drugs, eg, amiodarone for rhythm control), tobacco use (doubled), race (doubled); TE = thromboembolism.

Table Graphic Jump Location
TABLE 3  ] SAMe-TT2R2 Score in Patients With Atrial Fibrillation With Various Types of Events

Data are presented as mean ± SD unless otherwise indicated. VKA = vitamin K antagonist. See Table 2 legend for expansion of other abbreviations.

A significantly higher mean SAMe-TT2R2 score was seen in patients with labile INR while taking VKA (P = .0001) (Table 3). In patients treated with a VKA, a higher mean SAMe-TT2R2 score was also found for patients in whom stroke/TE (P < .0001), severe bleeding (P < .0001), or major BARC bleeding (P < .0001) developed and death occurred (P = .001) during follow-up (Table 3). There were no significant differences in SAMe-TT2R2 score for these events among patients not treated with a VKA.

A comparison of patients taking VKAs with an SAMe-TT2R2 score of 0 to 2 (ie, low-moderate risk) with those with a score > 2 (high risk of poor TTR) using Kaplan-Meier analysis showed a significant increase in risk of severe bleeding events (risk ratio [RR], 1.38; 95% CI, 1.12-2.68; P = .002) (Fig 2) and major BARC bleeding (RR, 1.77; 95% CI, 1.29-2.44; P = .0005) (Fig 3). The differences were nonsignificant for stroke/TE (RR, 1.08; 95% CI, 0.85-1.38; P = .51) and death (RR, 1.07; 95% CI, 0.87-1.32; P = .53).

Figure Jump LinkFigure 2  Severe bleeding events in patients with atrial fibrillation treated with VKAs. RR = risk ratio. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3  Bleeding Academic Research Consortium-defined major bleeding events in patients with atrial fibrillation treated with VKAs. See Figure 1 and 2 legends for expansion of abbreviations.Grahic Jump Location

The predictive values (using C statistics) for various events when using the SAMe-TT2R2 score are shown in Table 4. Among the patients receiving VKAs, the SAMe-TT2R2 score was modestly predictive of labile INRs (C statistics approximately 0.58) as well as of stroke/TE, severe bleeding, major BARC bleeding, and death (C statistics, 0.54-0.57 for events) (Table 4). This was not the case for patients not taking VKAs (most had C statistics with lower limits of the 95% CI < 0.5).

Table Graphic Jump Location
TABLE 4  ] Comparison of C Statistics When Using the SAMe-TT2R2 Score for Determining the Risk of Various Events in Patients With Atrial Fibrillation

C statistic is calculated as area under the curve for the receiver operating characteristic. See Table 2 and 3 legends for expansion of abbreviations.

a 

SAMe-TT2R2 score as a continuous variable.

b 

SAMe-TT2R2 score as a categorical variable: low (0-1), moderate (2), or high (> 2) risk.

c 

SAMe-TT2R2 score as a categorical variable: low (0-2) or high risk (> 2).

In this analysis, we demonstrate for the first time in our knowledge that the SAMe-TT2R2 score predicts an increasing risk of severe bleeding and major BARC bleeding. A higher mean SAMe-TT2R2 score was seen in patients with labile INR while taking VKAs as well as in patients in whom stroke/TE, severe bleeding, and major BARC bleeding developed and death occurred during follow-up. Of note, the mean SAMe-TT2R2 score was higher in patients who did (vs did not) have adverse events but only among those who were taking VKAs, which argues strongly that the SAMe-TT2R2 score predicts poor TTR, which in turn leads to adverse events but does not otherwise directly predict adverse events.

The SAMe-TT2R2 score was developed as a simple way to assess the likelihood of a patient with AF having good or poor quality of anticoagulation control, thus, helping with decision-making about whether the patient could start receiving VKA therapy or be best treated with a non-VKA OAC agent.6,11 The SAMe-TT2R2 score contains simple clinical parameters, including sex, age, medical history, treatments (eg, interacting drugs), tobacco use (ie, smoking status), and race (non-white). Good or poor anticoagulation control (as reflected by average TTR) translates into outcomes, whether good or bad, in terms of stroke/TE and serious bleeding.1,2 Indeed, the present analysis shows that the SAMe-TT2R2 score can be particularly related to severe bleeding and major BARC bleeding, which are consequences of poor INR control. Apart from the bleeding end points, higher SAMe-TT2R2 score was also associated with stroke/TE and death at follow-up.

Among the patients taking VKAs, the SAMe-TT2R2 score was modestly predictive of labile INR, stroke/TE, severe bleeding, major BARC bleeding, and death. The SAMe-TT2R2 score was also designed as a way to determine which patients are likely to have a poor TTR rather than as a predictor for TE and bleeding events per se. This reflects the multifactorial nature of managing INRs and ensuring good anticoagulation control and may reflect our clinical definition of labile INR rather than a definition based on actual TTRs and INRs.

Stroke and bleeding risk can be related to traditional risk factors that include age and medical history, which are components of the SAMe-TT2R2 score12; thus, a relationship to stroke and bleeding could be expected. However, we emphasize that the objective was not to use the SAMe-TT2R2 score as a predictor for stroke or bleeding events in AF given the availability of simple, well-validated scores, such as CHA2DS2-VASc and HAS-BLED. Of note, there were no significant differences in SAMe-TT2R2 score for these events among patients not treated with a VKA. The fact that the SAMe-TT2R2 score has already been internally and externally validated to be related to achieved TTR during follow-up shows how this score can be practically applied to define patients likely to do well (or not) while receiving VKA therapy.6,11 We have also used some end points that are robustly defined, including stroke/TE, major BARC bleeding, and death. Indeed, alternatives to VKA therapy offer efficacy, relative safety, and convenience compared with anticoagulation with VKA therapy.5

This study has several limitations. The dataset is based on a hospitalized cohort of patients with AF, and the data may not be generalizable to the wider nonhospitalized AF population. The criteria used for labile INR were based on physician diagnosis and not on traditional equation-based calculations of TTR, such as the Rosendaal method.13 The population also has limited racial/ethnic diversity, which might affect generalizability to other ethnic populations. Additionally, residual confounding is very likely given the possibility of undiagnosed comorbidities that predispose to the outcomes studied. Indeed, baseline stroke and bleeding risks and the event rates during follow-up were not as different as one would expect for patients taking VKA vs patients not taking VKA. Other factors, such as treatment discontinuation (or temporary interruptions), could have influenced the overall treatment outcomes.

In conclusion, we demonstrate that the SAMe-TT2R2 score is predictive of an increasing risk of severe bleeding and major BARC bleeding, reflecting poor anticoagulation control (and labile INRs) in patients with AF receiving VKAs. Additional ongoing prospective validation studies would help to fully determine the practical application of this score in everyday clinical practice.

Author contributions: G. Y. H. L. and L. F. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. G. Y. H. L. contributed to the original hypothesis and study concept, data interpretation, drafting and revision of the manuscript, critical review of the manuscript for important intellectual content, and final approval of the manuscript; K. H., C. S.-E., and L. F. contributed to interpretation of the results, critical review of the manuscript for important intellectual content, and approval of the final manuscript; and L. F. contributed to data collection and analysis.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Lip has served as a consultant for Bayer AG; Astellas Pharma US, Inc; Merck, Sharp & Dohme; AstraZeneca plc; sanofi-aventis US LLC; Biotronik SE & Co.KG; Bristol-Myers Squibb/Pfizer, Inc; and Boehringer Ingelheim GmbH and has been on the speakers bureau for Bayer AG; Bristol-Myers Squibb/Pfizer, Inc; Boehringer Ingelheim GmbH; and sanofi-aventis US LLC. Dr Fauchier has served as a consultant for Bayer AG; Medtronic, Inc; and sanofi-aventis US LLC and has received funding for conference travel and educational symposia from Boehringer Ingelheim GmbH; Bayer AG; Medtronic, Inc; and sanofi-aventis US LLC. Drs Haguenoer and Saint-Etienne have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

AF

atrial fibrillation

BARC

Bleeding Academic Research Consortium

CHADS2

congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke or transient ischemic attack

CHA2DS2VASc

congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65 to 74 years, and sex category

HAS-BLED

hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs/alcohol concomitantly

INR

international normalized ratio

OAC

oral anticoagulation

RR

risk ratio

SAMe-TT2R2

sex female, age < 60 years, medical history (more than two comorbidities), treatment (interacting drugs, eg, amiodarone for rhythm control), tobacco use (doubled), race (doubled)

TE

thromboembolism

TTR

time in therapeutic range

VKA

vitamin K antagonist

Gallagher AM, Setakis E, Plumb JM, Clemens A, van Staa TP. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb Haemost. 2011;106(5):968-977. [CrossRef] [PubMed]
 
Gallego P, Roldan V, Marín F, et al. Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation. Thromb Haemost. 2013;110(6):1189-1198. [CrossRef] [PubMed]
 
De Caterina R, Husted S, Wallentin L, et al; European Society of Cardiology Working Group on Thrombosis Task Force on Anticoagulants in Heart Disease. General mechanisms of coagulation and targets of anticoagulants (section I). Position paper of the ESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease. Thromb Haemost. 2013;109(4):569-579. [CrossRef] [PubMed]
 
De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heart disease: current status and perspectives (section III). Position paper of the ESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease. Thromb Haemost. 2013;110(6):1087-1107. [CrossRef] [PubMed]
 
Potpara TS, Lip GY. Novel oral anticoagulants in non-valvular atrial fibrillation. Best Pract Res Clin Haematol. 2013;26(2):115-129. [CrossRef] [PubMed]
 
Apostolakis S, Sullivan RM, Olshansky B, Lip GYH. Factors affecting quality of anticoagulation control among patients with atrial fibrillation on warfarin: the SAMe-TT2R2score. Chest. 2013;144(5):1555-1563. [CrossRef] [PubMed]
 
Lip GY, Banerjee A, Lagrenade I, Lane DA, Taillandier S, Fauchier L. Assessing the risk of bleeding in patients with atrial fibrillation: the Loire Valley Atrial Fibrillation project. Circ Arrhythm Electrophysiol. 2012;5(5):941-948. [CrossRef] [PubMed]
 
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Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation. Chest. 2010;137(2):263-272. [CrossRef] [PubMed]
 
Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip GYH; Guideline Development Group for the NICE national clinical guideline for management of atrial fibrillation in primary and secondary care; Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100. [CrossRef] [PubMed]
 
Boriani G. Predicting the quality of anticoagulation during warfarin therapy: the basis for an individualized approach. Chest. 2013;144(5):1437-1438. [CrossRef] [PubMed]
 
Lip GY. Stroke and bleeding risk assessment in atrial fibrillation: when, how, and why? Eur Heart J. 2013;34(14):1041-1049. [CrossRef] [PubMed]
 
Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993;69(3):236-239. [PubMed]
 

Figures

Figure Jump LinkFigure 1  Study population. SAMETT2R2 = sex female, age < 60 y, medical history (more than two comorbidities), treatment (interacting drugs, eg, amiodarone for rhythm control), tobacco use (doubled), race (doubled); VKA = vitamin K antagonist.Grahic Jump Location
Figure Jump LinkFigure 2  Severe bleeding events in patients with atrial fibrillation treated with VKAs. RR = risk ratio. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3  Bleeding Academic Research Consortium-defined major bleeding events in patients with atrial fibrillation treated with VKAs. See Figure 1 and 2 legends for expansion of abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1  ] Characteristics of the Patients With Atrial Fibrillation

Data are presented as mean ± SD or No. (%). ACE = angiotensin-converting enzyme; AT2 = angiotensin II; CHADS2 = congestive heart failure, hypertension, age ≥ 75 y, diabetes, prior stroke or transient ischemic attack; CHA2DS2-VAS = congestive heart failure, hypertension, age ≥ 75 y, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65 to 74 y, and sex category; ESC = European Society of Cardiology; HAS-BLED = hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 y), drugs/alcohol concomitantly; ICD = implantable cardioverter defibrillator; LVEF = left ventricular ejection fraction; OAC = oral anticoagulation.

Table Graphic Jump Location
TABLE 2  ] Labile INR, Stroke/TE, Clinically Relevant Bleeding, and Mortality by Category of SAMe-TT2R2 Score

Data are presented as No. (%) or hazard ratio (95% CI). BARC = Bleeding Academic Research Consortium; INR = international normalized ratio; Ref = reference; SAMe-TT2R2 = sex female, age < 60 y, medical history (more than two comorbidities), treatment (interacting drugs, eg, amiodarone for rhythm control), tobacco use (doubled), race (doubled); TE = thromboembolism.

Table Graphic Jump Location
TABLE 3  ] SAMe-TT2R2 Score in Patients With Atrial Fibrillation With Various Types of Events

Data are presented as mean ± SD unless otherwise indicated. VKA = vitamin K antagonist. See Table 2 legend for expansion of other abbreviations.

Table Graphic Jump Location
TABLE 4  ] Comparison of C Statistics When Using the SAMe-TT2R2 Score for Determining the Risk of Various Events in Patients With Atrial Fibrillation

C statistic is calculated as area under the curve for the receiver operating characteristic. See Table 2 and 3 legends for expansion of abbreviations.

a 

SAMe-TT2R2 score as a continuous variable.

b 

SAMe-TT2R2 score as a categorical variable: low (0-1), moderate (2), or high (> 2) risk.

c 

SAMe-TT2R2 score as a categorical variable: low (0-2) or high risk (> 2).

References

Gallagher AM, Setakis E, Plumb JM, Clemens A, van Staa TP. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb Haemost. 2011;106(5):968-977. [CrossRef] [PubMed]
 
Gallego P, Roldan V, Marín F, et al. Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation. Thromb Haemost. 2013;110(6):1189-1198. [CrossRef] [PubMed]
 
De Caterina R, Husted S, Wallentin L, et al; European Society of Cardiology Working Group on Thrombosis Task Force on Anticoagulants in Heart Disease. General mechanisms of coagulation and targets of anticoagulants (section I). Position paper of the ESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease. Thromb Haemost. 2013;109(4):569-579. [CrossRef] [PubMed]
 
De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heart disease: current status and perspectives (section III). Position paper of the ESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease. Thromb Haemost. 2013;110(6):1087-1107. [CrossRef] [PubMed]
 
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