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

Highlights

• In atrial fibrillation, SAMe-TT2R2 score identifies patients with foreseeable poor INR control.

• Studies of the SAMe-TT2R2 score in venous thrombosis showed conflicting results.

• In this study, SAMe-TT2R2 score discriminated those patients with high risk of poor INR control.

• However, predictive capacity of the SAMe-TT2R2 score in venous thrombosis is low.

Abstract

Background

The time in therapeutic range (TTR) of patients with venous thromboembolism (VTE) treated with vitamin K antagonists (VKA) is usually below recommended, leading to higher frequency of vascular events, bleeding and mortality. The SAMe-TT2R2 prediction score discriminates those patients with high or low probability of obtaining poor INR control and its use is recommended in patients with atrial fibrillation. Its usefulness has been evaluated in patients with VTE, with conflicting results.

Method

We included consecutive patients enrolled in Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective multicenter VTE registry, treated with VKA for >90 days and a minimum of 3 INR determinations. We analyzed the relationship between the SAMe-TT₂R₂ score and TTR, determined by the Rosendaal method and by the percentage of INR determinations (after excluding the first month). A ROC curve was calculated considering a cut-off point of TTR ≥65% for good anticoagulation control.

Results

3893 patients were included and classified in high (1411 patients) or low (2482 patients) probability of obtaining poor INR control according to the total score obtained (0–1 points versus 2 points, respectively). TTR, calculated by direct method and Rosendaal method, was 51.2 (±23.4) and 55.4 (±25.9) in the high probability group; and 54.4 (±23.0) and 58.2 (±25.6) in the low probability group, respectively (p < 0.001 for both comparisons). The outcomes were similar between groups. The predictive capacity of the SAMe-TT2R2 score showed an area under the ROC curve of 0.54 (CI 95% 0.52–0.56) and 0.53 (CI 95% 0.51–0.55).

Conclusions

In patients with VTE treated with VKA, the SAMe-TT2R2 score discriminated those patients with high probability of obtaining poor INR control, but with a low predictive capacity. Further studies are required to assess the usefulness of the score in clinical decision-making.

Introduction

Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE) and constitutes the third cause of morbi-mortality in the USA and Europe [[1], [2], [3], [4]]. Currently, the direct oral anticoagulants (DOACs) are the first choice of therapy in VTE patients without cancer [5,6] and in those with atrial fibrillation (AF) [7]. They have all demonstrated a similar efficacy than the vitamin K antagonists (VKAs) and a lower risk for bleeding in randomized trials. In addition, real-life studies have confirmed these results [8] although up to 24% of patients [9,10] were not represented in these trials [11,12].

The VKAs have a narrow therapeutic window, and require periodic INR monitoring and frequent dose adjustments to maintain the intensity of anticoagulation. The efficacy and safety of VKAs depend on the so-called time in therapeutic range (TTR), which is measured by the Rosendaal method (that takes into account the time interval between INR determinations) [13] or the direct method [14]. In patients with VTE, TTR values <70% have been associated with a higher frequency of vascular events, bleeding and mortality [15]. In randomized trials, the TTR is usually below recommended: around 64% in AF patients [16,17] and 57–63% [18] in VTE patients. In real-life studies it is even lower: 57–61% [19]. Thus, a reliable tool to identify patients at risk of poor INR control would be very useful. In patients with foreseeable poor INR controls, physicians may implement measures for better control or consider switching to DOACs.

The SAMe-TT2R2 [20] score is a simple score based on clinical risk factors (Sex, Age, Medical history, Treatment, Tobacco and Race), to discriminate patients with low or high probability of poor INR control (TTR <65%). It was first validated in patients with AF [7,21,22], and it has been evaluated in VTE patients in a few studies, with conflicting findings [[23], [24], [25], [26]].