Abstract
Background
The TIMI‐AF score predicts poor outcomes in patients with atrial fibrillation (AF) and guides selection of anticoagulant therapy by identifying clinical benefit of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA).
Hypothesis
Our objective was to determine the ability to predict cardiovascular events according to the TIMI‐AF score in a real‐world population.
Methods
Retrospective observational study of VKA‐naïve patients with AF was seen at a cardiology outpatient clinic in Spain between November 2012 and August 2014. We recorded adverse events (myocardial infarction, systemic embolism or stroke, major bleeding, and death).
Results
The study population comprised of 426 patients (50.7% men, mean age, 69 ± 14 years). The TIMI‐AF score identified 372 patients (87.3%) with a low risk, 50 patients (11.7%) with an intermediate risk, and 4 patients (0.9%) with a high risk. After a mean follow‐up of 423.4 ± 200.1 days, 37 patients (9%) experienced an adverse event. Patients with a TIMI‐AF score ≥ 7 had a poorer cardiovascular prognosis (HR, 6.1; 95%CI, 3.2‐11.7; P < 0.001). The area under the ROC curve of TIMI‐AF was 0.755 (95%CI, 0.669‐0.840; P < 0.001), which was greater than that of CHA2DS2VASc (0.641; 95%CI, 0.559‐0.724; P = 0.004), HAS‐BLED (0.666; 95%CI, 0.578‐0.755; P < 0.001), and SAMeTT2R2 (0.529; 95%CI, 0.422‐0.636; P = 0.565). Similar results were obtained in relation to the net clinical outcome (life‐threatening bleeding, disabling stroke, or all‐cause mortality).
Conclusions
The TIMI‐AF risk score can identify patients who are at greater risk of cardiovascular events and a poor net clinical outcome with a better diagnostic yield than CHA2DS2VASc, HAS‐BLED, and SAMeTT2R2.
Keywords: anticoagulants, atrial fibrillation, cardiovascular prognosis, TIMI‐AF score
1. INTRODUCTION
Atrial fibrillation (AF) is the most common arrhythmia and is associated with high morbidity and mortality.1 Oral anticoagulation with vitamin K antagonists (VKA) has been the treatment of choice for over half a century, since it reduces the risk of ischemic stroke and increases survival.2 However, management of VKA‐based therapy is complex. Consequently, a significant percentage of patients are not anticoagulated or discontinue therapy early.3, 4 Direct oral anticoagulants (DOACs) have emerged as an alternative to VKA in patients with nonvalvular AF.5, 6, 7, 8
Most risk scores, as CHA2DS2VASc (2 points = stroke/transient ischemic attack and age ≥75 years; 1 point = congestive heart failure, hypertension, diabetes mellitus, vascular disease, age 65 to 74 years, female sex) and HAS‐BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), evaluate the risk of thrombosis9, 10, 11, 12, 13 or major hemorrhage.14, 15, 16, 17 Although the scores are useful for identifying patients who require oral anticoagulation and closer follow‐up, they cannot identify which patients derive particular benefit from DOACs or VKA. The SAMe‐TT2R2 (1 point = female sex, age <60 years, medical history—at least two of the following: hypertension, diabetes, coronary artery disease/myocardial infarction, peripheral arterial disease, congestive heart failure, previous stroke, pulmonary disease, hepatic or renal disease, interacting drugs with VKA; 2 points = current tobacco use and race non‐Caucasian) score could prove to be a useful tool, since it predicts VKA‐naïve patients who are likely to have poor control of the international normalized ratio (INR).18
The recently published Thrombolysis in Myocardial Infarction‐Atrial Fibrillation (TIMI‐AF) score (3 points = age ≥ 75 and left ventricular ejection fraction <30%; 2 points = age 66 to 74, left ventricular ejection fraction 30% to 49%, hemoglobin <13 g/dL and non‐white race; 1 point = unknown left ventricular ejection fraction, baseline AF or atrial flutter, prior ischemic stroke, creatinine ≥ 110 μmol/L, male sex, diabetes mellitus, carotid disease history, and prior myocardial infarction) identifies which patients will have a poor net clinical outcome of life‐threatening bleeding, disabling stroke, or all‐cause mortality on VKA, and could therefore benefit from treatment with edoxaban.19 Its performance is unknown in real‐world populations with different thromboembolic risks and receiving treatment with various DOACs. Similarly, we do not know how TIMI‐AF performs better than SAMe‐TT2R2. We evaluated the ability to predict cardiovascular events according to the TIMI‐AF score in a sample of VKA‐naïve outpatients with nonvalvular AF and to compare the results with those obtained using CHA2DS2VASc, HAS‐BLED, and SAMe‐TT2R2.
2. METHODS
We performed a retrospective observational study of patients seen between November 2012 and August 2014 at a specialist AF clinic that belonged to a secondary‐level hospital in Marbella (Spain). The clinic receives patients seen in the emergency department with AF episodes and gives priority to those who have not previously undergone a cardiology work‐up. The study population comprised VKA‐naïve patients with atrial flutter or nonvalvular AF. Patients with metallic prostheses or moderate or severe rheumatic mitral stenosis were excluded. Clinical and demographic data were collected from the clinical history.
We recorded adverse events (myocardial infarction, systemic embolism or stroke, major bleeding, and death) as well as serious net clinical outcomes (life‐threatening bleeding, disabling stroke, or all‐cause mortality) using telephone interviews and the electronic clinical history. Major bleeding was defined based on the classification of the International Society on Thrombosis and Hemostasis.20 Myocardial infarction was defined according to the Third universal definition of myocardial infarction (2012).21 The analysis was performed on an intention‐to‐treat basis. Quantitative variables are expressed as mean ± SD and qualitative variables as frequencies and percentages. Event‐free survival was analyzed using Kaplan‐Meier curves and the log‐rank test. We performed a univariate analysis based on the χ 2 test (or Pearson P test) for qualitative variables and with the t test for quantitative variables. The Mann‐Whitney test was utilized in the case of a non‐normal distribution. Normality was assessed using the Kolmogorov‐Smirnov and Shapiro‐Wilks tests for samples larger and smaller than 50 patients, respectively. Associations between risk scores and cardiovascular events were analyzed using Cox regression. Statistical significance was set at P < 0.05. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic yield of the various risk scores for identification of patients with a poorer cardiovascular prognosis. The statistical analysis was performed using IBM® SPSS® Statistics for Macintosh, Version 20.0.
The study was performed according to the usual conditions of real‐world clinical practice, with no therapeutic interventions. Informed consent was not requested given the retrospective nature of the study. The data were anonymized before processing. The protocol was approved by the local ethics committee.
3. RESULTS
The study population comprised 426 patients with nonvalvular AF (216 men [50.7%]; mean age, 69 ± 14 years; mean CHA2DS2VASc score, 2.7 ± 1.7; mean HAS‐BLED score, 1.1 ± 0.8). Table 1 shows the main baseline characteristics of the study population: 7.5% had a history of transient ischemic attack, stroke or systemic embolism; 8.7% had a history of ischemic heart disease; 18.2% had structural heart disease, mainly hypertensive heart disease (6.1% with hemodynamically significant valve disease). The mean TIMI‐AF score was 3.9 ± 2.2; the mean SAMe‐TT2R2 score was 1.5 ± 1.0. The TIMI‐AF score identified 50 patients (11.7%) with a moderate risk and 4 (0.9%) with a high risk; in addition, 188 patients (44.1%) had a SAMe‐TT2R2 score ≥ 2. When the 59 patients with a CHA2DS2VASc score of 0 (ie, patients with no indication for oral anticoagulation a priori) were excluded, 54 (14.7%) had an intermediate or high risk according to the TIMI‐AF score and 154 (42%) had a SAMe‐TT2R2 ≥ 2. Thus, applying both scales identified 179 patients (48.8%) in whom a DOAC could be preferable to a VKA. As for drugs prescribed, 71.8% of patients received anticoagulants (VKA, 21.4%; dabigatran, 19.5%; rivaroxaban, 18.6%; apixaban, 11.5%; enoxaparin, 0.9%), 11.7% single antiplatelet therapy, 0.7% dual antiplatelet therapy, and 2.1% concomitant antiplatelet and anticoagulant therapy. The maximum dose was prescribed in 71.6% of patients taking DOACs.
Table 1.
Baseline characteristics of the samplea
| Baseline characteristics n = 426 (%) | |
|---|---|
| Female sex | 210 (49.3) |
| Age (years) | 71 [62‐80] |
| White race | 417 (97.9) |
| Arterial hypertension | 267 (62.7) |
| Diabetes mellitus | 96 (22.5) |
| Smoking (previous 2 y) | 43 (12.2) |
| Dyslipidemia | 157 (36.9) |
| Heart failure or LVEF < 40% | 41 (9.6) |
| LVEF ≥ 60% | 396 (93) |
| TIA, stroke, or peripheral embolism | 32 (7.5) |
| Vascular diseaseb | 34 (8.0) |
| Lung disease | 61 (14.3) |
| Carotid disease | 2 (0.5) |
| Atrial flutterc | 52 (12.2) |
| Paroxysmal or persistent AF | 405 (95.1) |
| Permanent AF | 21 (4.9) |
| Sinus rhythm at visit | 232 (54.5) |
| Hemoglobin <13 g/dL | 124 (29.1) |
| Creatinine (mg/dL) | 0.8 [0.7‐1.0] |
| Stage 3–5 chronic kidney disease | 75 (17.6) |
| CKD‐EPI (mL/min/1.73 m2) | 83.6 [67.5‐95.3] |
| Hba1c (%) | 5.9 [5.7‐6.4] |
| LDL cholesterol (mg/dL) | 107.8 ± 41.4 |
| Structural heart disease | 78 (18.2) |
| Severe mitral valve disease | 26 (6.1) |
| Ischemic heart disease | 37 (8.7) |
| Acute myocardial infarction | 14 (3.3) |
| CHADS2 | 1.0 [1.0‐2.0] |
| CHA2DS2VASc | 3 [1.0‐4.0] |
| CHA2DS2VASc = 0 | 59 (13.8) |
| CHA2DS2VASc = 1 | 51 (12.0) |
| CHA2DS2VASc ≥ 2 | 316 (74.2) |
| HAS‐BLED | 1.0 [1.0–2.0] |
| HAS‐BLED ≥ 3 | 20 (4.7) |
| TIMI‐AF score | 4.0 [2.0‐5.0] |
| Low risk (0‐6) | 372 (87.3) |
| Intermediate risk (7‐9) | 50 (11.7) |
| High risk (≥10) | 4(0.9) |
| SAMe‐TT2R2 score | 1.0 [1.0–2.0] |
| SAMe‐TT2R2 ≥ 2 | 188 (44.1) |
| Treatment with antiplatelet agents | 63 (14.8) |
| Single antiplatelet therapy | 50 (11.7) |
| Dual antiplatelet therapy | 3 (0.7) |
| Anticoagulant + antiplatelet agent | 9 (2.1) |
| Treatment with anticoagulants | 306 (71.8) |
| VKA | 91 (21.4) |
| Apixaban | 49 (11.5) |
| Dabigatran | 83 (19.5) |
| Rivaroxaban | 79 (18.6) |
| LMWH | 4 (0.9) |
| Treatment with antiarrhythmic agents | 65 (15.3) |
| Dronedarone | 26 (6.1) |
| Amiodarone | 24 (5.6) |
| Class IC | 15 (3.5) |
Abbreviations: AF, atrial fibrillation; CKD‐EPI, Chronic Kidney Disease Epidemiology Collaboration; LDL, low‐density lipoprotein; LMWH, low‐molecular‐weight heparin; LVEF, left ventricular ejection fraction; VKA, vitamin K antagonist.
Qualitative variables are expressed as n (%). Quantitative variables are expressed as mean ± SD. In cases where the criteria for normality are not fulfilled, variables are expressed as median [IQR].
Peripheral artery disease, myocardial infarction, aortic atheromatous plaques.
The same patient can present atrial fibrillation and atrial flutter.
After a mean follow‐up of 423.4 ± 200.1 days, 37 patients (9%) experienced an adverse event (4 nonfatal acute myocardial infarctions, 3 strokes or systemic embolisms, 9 major bleeds, and 27 deaths). Fourteen patients (3.3%) were lost to follow‐up. The univariate analysis (Table 2) showed that the variables associated with greater incidence of adverse events were age, weight <60 kg, diabetes mellitus, HbA1c, heart failure, depressed ejection fraction, vascular disease, ischemic heart disease, kidney failure, creatinine, estimated glomerular filtration rate, estimated creatinine clearance, anemia, hemoglobin, use of clopidogrel, use of low doses of DOACs, left ventricular ejection fraction, heart rate, and diastolic arterial pressure. Patients with a TIMI‐AF score ≥ 7 (HR, 6.1; 95%CI, 3.2‐11.7; P < 0.001), CHA2DS2VASc ≥ 2 (HR, 6.1; 95%CI, 1.5‐25.4; P = 0.013), or HAS‐BLED ≥ 3 (HR, 6.9; 95%CI, 3.1‐15.1; P < 0.001) were associated with a greater incidence of adverse events. In contrast, the SAMe‐TT2R2 score was not correlated with prognosis (HR, 1.0; 95%CI, 0.5‐1.9; P = 0.991). The same findings were revealed by the Kaplan‐Meier survival curves (Figure 1).
Table 2.
Univariate analysis: Factors associated with adverse events (death, myocardial infarction, systemic embolism or stroke, or major bleeding)
| Variables | Events | P |
|---|---|---|
| Age (years) | 78.0 ± 10.1 vs 68.1 ± 14.5 | 0.001 |
| Weight ≤ 60 kg (%) | 16 vs 6.2 | 0.037 |
| Arterial hypertension (%) | 8.4 vs 9.9 | 0.607 |
| Heart failure and/or LVEF < 40% (%) | 19.5 vs 7.8 | 0.021 |
| LVEF (%) | 58.6 ± 9.3 vs 60.9 ± 6.5 | 0.05 |
| TIA, stroke, or peripheral embolism (%) | 3.1 vs 9.5 | 0.340 |
| Vascular diseasea (%) | 20.6 vs 7.9 | 0.023 |
| Previous bleeding or predisposition (%) | 18.4 vs 8 | 0.065 |
| Ischemic heart disease (%) | 22.2 vs 7.7 | <0.001 |
| Diastolic blood pressure (mmHg) | 68.4 ± 10.8 vs 76.2 ± 11.8 | 0.001 |
| Heart rate (bpm) | 87.2 ± 24.3 vs 77.7 ±21.1 | 0.015 |
| Creatinine (mg/dL) | 1.3 ± 0.9 vs 0.9 ±0.3 | 0.015 |
| MDRD‐4 (mL/min/1.73 m2) | 71.9 ± 34.5 vs 89.9 ±27.7 | 0.005 |
| CKD‐EPI (mL/min/1.73 m2) | 64.1 ±28.9 vs 81.7 ±21.1 | 0.001 |
| Cockcroft‐gault (mL/min) | 71.2 ± 45.4 vs 93.4 ±40.5 | 0.005 |
| Stage 3–5 chronic kidney disease (%) | 24.4 vs 7.3 | 0.001 |
| Hemoglobin (g/dL) | 12.6 ±1.7 vs 14.2 ±4.7 | <0.001 |
| HbA1C (%) | 7.2 ±1.6 vs 6.2 ±0.9 | 0.032 |
| Anticoagulation (%) | 8.7 vs 9.8 | 0.42 |
| Anticoagulation with low‐dose DOACs (%) | 14.8 vs 6.1 | 0.003 |
| Clopidogrel (%) | 37.5 vs 8.4 | 0.027 |
| TIMI‐AF score ≥ 7 (%) | 31.5 vs 5.6 | <0.001 |
| CHA2DS2VASc ≥ 2 (%) | 11.3 vs 2 | 0.004 |
| HAS‐BLED ≥3 (%) | 42.1 vs 7.4 | <0.001 |
| SAMe‐TT2R2 ≥ 2 (%) | 9.3 vs 8.7 | 0.820 |
| TIMI‐AF SCORE | ||
| Age (≤ 65 years vs 66‐74 y vs ≥ 75 y) (%) | 2.5 vs 5.3 vs 15.8 | <0.001 |
| LVEF (<30% vs 30%‐49% vs ≥50% vs unknown) (%) | 100 vs 16.7 vs 7.8 vs 37.5 | <0.001 |
| Hemoglobin <13 g/dL (%) | 16.5 vs 5.8 | 0.001 |
| Non‐white race (%) | 25 vs 8.7 | 0.156 |
| ECG: AF or atrial flutter (%) | 11.7 vs 6.7 | 0.077 |
| Creatinine ≥1.24 mg/dL (%) | 28.2 vs 7 | <0.001 |
| Ischemic stroke (%) | 0 vs 9.4 | 0.239 |
| Male sex (%) | 10.1 vs 7.8 | 0.406 |
| Diabetes mellitus (%) | 14.7 vs 7.3 | 0.025 |
| Previous myocardial infarction (%) | 14.3 vs 8.8 | 0.363 |
| Carotid artery disease (%) | 0.0 vs 9 | 1.000 |
Abbreviations: AF, atrial fibrillation; CKD‐EPI, Chronic Kidney Disease Epidemiology Collaboration; LDL, low‐density lipoprotein; LMWH, low‐molecular‐weight heparin; LVEF, left ventricular ejection fraction; MDRD, Modification of Diet in Renal Disease; VKA, vitamin K antagonist.
Peripheral artery disease, myocardial infarction, aortic atheromatous plaques.
Figure 1.
Kaplan–Meier estimates for the first adverse event (myocardial infarction, systemic embolism or stroke, major bleeding and death) using the CHA2DS2VASc, TIMI‐AF, SAMe‐TT2R2, and HAS‐BLED scores
The area under the ROC curve for the TIMI‐AF score shows a better diagnostic yield than the other scores for predicting cardiovascular events (Figure 2). The area under the ROC curve was 0.755 (95%CI, 0.669‐0.840; P < 0.001), which was greater than that observed for CHA2DS2VASC (0.641; 95%CI, 0.559‐0.724; P = 0.004), HAS‐BLED (0.666; 95%CI, 0.578‐0.755; P < 0.001), and SAMeTT2R2 (0.529; 95%CI, 0.422‐0.636; P = 0.565). A TIMI‐AF value ≥ 7 revealed a sensitivity of 45.9%, specificity of 90.1%, positive predictive value of 31.5%, and negative predictive value of 94.4% (Table 3).
Figure 2.
ROC curves for the TIMI‐AF, SAMe‐TT2R2, CHA2DS2VASc, and HAS‐BLED scores
Table 3.
Validity and safety of the TIMI‐AF, SAMe‐TT2R2, CHA2DS2VAsc, and HAS‐BLED risk scores to predict cardiovascular events (myocardial infarction, systemic embolism or stroke, major bleeding, and death)
| Score | Sensitivity | Specificity | PPV | NPV | AUC |
|---|---|---|---|---|---|
| TIMI‐AF ≥ 7 | 45.9 | 90.1 | 31.5 | 94.4 | 0.755 (95%CI, 0.669‐0.840; P < 0.001) |
| CHA2DS2VASc ≥ 2 | 94.6 | 26.7 | 11.3 | 98 | 0.641 (95%CI, 0.559‐0.724; P = 0.004) |
| HAS‐BLED ≥ 3 | 21.6 | 97.1 | 42.1 | 92.6 | 0.666 (95%CI, 0.578‐0.755; P < 0.001) |
| SAME‐TT2R2 ≥ 2 | 45.9 | 56.0 | 9.3 | 91.3 | 0.529 (95%CI, 0.422‐0.636; P = 0.565) |
PPV, positive predictive value; NPV, negative predictive value; AUC, area under de receiver operating characteristic curve.
Thirty patients (7.3%) experienced a net clinical outcome (3 disabling strokes, 3 life‐threatening bleeding, and 27 deaths). Patients with a TIMI‐AF score ≥ 7 were associated with a greater incidence of net clinical outcomes (24.1 vs 4.7%; HR, 5.5; 95%CI, 2.6‐11.3; P < 0.001). In contrast, the SAMe‐TT2R2 score was not correlated with prognosis (HR, 1.0; 95%CI, 0.5‐2.1; P = 0.946). The area under the ROC curve for TIMI‐AF score was 0.663 (95%CI, 0.548‐0.778; P = 0.003), which was greater than that observed for CHA2DS2VASC (0.598; 95%CI, 0.505‐0.69; P = 0.075), HAS‐BLED (0.583; 95%CI, 0.466‐0.7; P = 0.13), and SAMeTT2R2 (0.513; 95%CI, 0.405‐0.621; P = 0.806).
3.1. Patients who had prescribed VKA
Eight patients (8.8%) who had prescribed VKA (n = 91) experienced an adverse event (two nonfatal acute myocardial infarctions, three strokes or systemic embolisms, two major bleeds, and four deaths). The incidence of adverse events was higher in those with a TIMI‐AF score ≥ 7 (33.3 vs 5.1%; HR, 5.6; 95%CI, 1.4‐23.1; P = 0.016) and SAMeTT2R2 ≥ 2 (12.5 vs 5.9%; HR, 2.3; 95%CI 0.5‐9.7; P = 0.253). The area under the ROC curve for TIMI‐AF score was 0.702 (95%CI, 0.481‐0.923; P = 0.06), which was greater than that observed for CHA2DS2VASC (0.584; 95%CI, 0.403‐0.766; P = 0.433), HAS‐BLED (0.556; 95%CI, 0.331‐0.782; P < 0.599), and SAMeTT2R2 (0.602; 95%CI, 0.397‐0.806; P = 0.344).
4. DISCUSSION
Ours is the first study to show the ability to predict cardiovascular events and a serious net clinical outcome according to TIMI‐AF under real‐world conditions in a population of VKA‐naïve patients with nonvalvular AF who have received various antiplatelet and anticoagulant treatments. The study also shows the correlation between TIMI‐AF and SAMe‐TT2R2. If we extrapolate the results of Fanola et al19 we can see that TIMI‐AF identifies one of every eight patients with a greater risk of serious adverse events (disabling stroke, all‐cause death, or life‐threatening bleeding) seen in the AF clinic. While Fanola et al showed that more than one‐third of patients were classified as having an intermediate or high risk, we found that this percentage fell to 14.7% of patients with a CHA2DS2VASc score > 0. The ENGAGE AF‐TIMI 48 trial only included patients with a CHADS2 ≥ 2, that is, patients with a greater risk of complications. In our sample, on the other hand, thromboembolic risk was lower and the percentage of patients with previous stroke was much lower.
If patients with a low thromboembolic risk (CHA2DS2VASc = 0) are excluded from the analysis, 14.7% had a TIMI‐AF score ≥ 7 and 42% had a SAMe‐TT2R2 score ≥ 2. There were no significant differences in the distribution of cardiovascular events according to this scale with respect to TIMI‐AF. Only 29 patients had high scores with both scales. When both scales are applied, we can identify one of every two patients in whom it would be preferable to start therapy with a DOAC. This finding is interesting, as it proposes the hypothesis that both scales are complementary for identification of VKA‐naïve patients with AF who can be better managed with DOACs. There are two possible explanations for this observation. First, it depends on the factors involved. Second, the SAMe‐TT2R2 is more sensitive, since it only requires 2 points whereas TIMI‐AF needs ≥ 7 points and the more important variables only have 3 points.19, 22
Our study reproduced the results of Fanola et al with respect to the predictive ability of the TIMI‐AF score. In patients with a score ≥ 7, net clinical outcomes and cardiovascular events were five to six times more frequent and the ROC curves showed that diagnostic yield was clearly better than with CHA2DS2VASc and HAS‐BLED. In contrast, SAMe‐TT2R2 was not correlated with cardiovascular prognosis. This observation could be explained by the fact that the usefulness of this scale is based on identifying patients who are at greater risk of poor control of the INR when under treatment with VKA. This in turn is associated with a poorer cardiovascular prognosis.23 However, in our sample, only 21.4% of patients were prescribed VKA, whereas 49.6% were taking DOACs. It is to be expected that the ability to predict events with this scale is lower or negligible in patients receiving DOACs. To our knowledge, this is the first experience with the SAMe‐TT2R2 scale in a population treated with DOACs.
Clinical practice guidelines make differing recommendations on the oral anticoagulant of choice. Guidelines from Europe24 and Canada25 prioritize the use of DOACs over VKA for most patients. However, American guidelines26 and the NICE guidelines27 consider DOACs to be equal and advocate a joint decision with the patient. While cost‐effective, these drugs do imply an additional cost.28 The current world economic framework makes it necessary to prioritize the use of these drugs in patients for whom they have a clear added value. Both in health systems with more limited resources and in those where the patient covers the cost of medication, it is important to have tools such as the TIMI‐AF score.
4.1. Study limitations
Our study is subject to a series of limitations. The sample is small and restricted to a single hospital. Given the observational and retrospective nature of the study, it is not possible to establish associations of causality or rule out confounders that affect the results. The specialist AF clinic receives mainly patients attended in the emergency department without a previous cardiology work‐up or who have to undergo electrical cardioversion. This could have led to a selection bias in favor of patients with incipient disease and a lower thromboembolic risk. We did not evaluate the time in therapeutic range among patients who had been prescribed VKA or its possible association with cardiovascular events. The most frequently used VKA in our center is acenocoumarol, which has a shorter half‐life than warfarin and could be associated with less stable INR values. According to the Rosendaal method,29 it is estimated that in our setting, INR is adequately controlled in 69.1% of patients. Finally, the TIMI‐AF score can identify patients at particular risk of adverse events who would benefit from safer therapy, such as edoxaban. It is unknown whether these findings can be extrapolated to other DOACs. In ENGAGE AF‐TIMI 48, an interaction was recorded between previous experience with VKA and the study results that was not reproduced in other pivotal trials.30 It should be noted as a strength of our work that the percentage of follow‐up losses has been very low.
5. CONCLUSIONS
In conclusion, in our population of VKA‐naïve patients with nonvalvular AF, the TIMI‐AF score identified patients at greater risk of cardiovascular events and a poor net clinical outcome and had a better diagnostic yield than the CHA2DS2VASc and HAS‐BLED scores. Joint application of SAMe‐TT2R2 and TIMI‐AF identified one of every two patients in whom DOAC would be a better therapeutic option than a VKA. In our sample, which contained a high proportion of patients treated with DOACs, the SAMe‐TT2R2 score was not associated with cardiovascular prognosis.
ACKNOWLEDGEMENTS
We want to thank Dr. Jorge Andrés Muñoz Robles and Carlos Ramos Ortiz for their support and wise advice.
Conflict of interest
Dr. Christian T. Ruff received honoraria from Daiichi Sankyo, Boehringer ingelheim, Bayer and Portola as a consultant and received research grants from Daichii Sankyo. Dr. Alejandro I. Pérez Cabeza received honoraria from Daiichi Sankyo and Bayer as a consultant. Dr. Francisco Ruiz Mateas received honoraria from Bayer and Boehringer ingelheim as a consultant.
Pérez Cabeza AI, Bravo Marques R, Chinchurreta Capote PA, et al. TIMI‐AF score and cardiovascular events in vitamin K antagonists‐naïve outpatients with atrial fibrillation. Clin Cardiol. 2018;41:1252–1258. 10.1002/clc.23035
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