By Michael H. Crawford, MD

Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: A new, simpler score for stroke risk prediction in atrial fibrillation patients uses biomarkers to supplant many clinical variables and outperforms the CHA2DS2-VASc score in two large cohorts.

SOURCE: Oldgren J, Hijazi I, Lindback J, et al. Performance and validation of a novel biomarker based stroke risk score for atrial fibrillation. Circulation 2016;134:1697-1707.

Current guidelines recommend the use of the CHA2DS2-VASc score to risk stratify patients with atrial fibrillation (AF) for stroke risk. This score is composed entirely of clinical variables. A newer score, ATRIA, also includes a measure of renal function. Since certain biomarkers have been shown to be powerful risk predictors, investigators derived a new risk score that included biomarkers from the almost 15,000 patients in the ARISTOTLE trial (apixaban vs. warfarin in AF). This new score was called ABC for Age, Biomarkers (NT-proBNP and high-sensitivity troponins), and Clinical history of prior stroke. In this population, it outperformed the CHA2DS2-VASc score. The purpose of this study was to validate that the ABC score in the RE-LY trial (dabigatran vs. warfarin), which included more than 8,000 patients at 951 sites in 44 countries who had AF and at least one clinical risk factor for stroke. Baseline patient characteristics for RE-LY and ARISTOTLE were similar, except that median age (72 years) was higher in RE-LY. There were 219 adjudicated strokes or systemic embolism events, or 1.36 per 100 patient years. Stroke risk groups were predefined as low (0-1% per year), medium (1-2%), or high (> 2%). Stroke rate for the low-risk group was 0.76 per 100 patient years, 1.48 for medium risk, and 2.6 for high risk. These results were similar when troponin I or T were used. The ABC score outperformed CHA2DS2-VASc (C index 0.65 vs. 0.60) and ATRIA (0.61). Also, the ABC score identified patients at higher and lower risk within each risk category in the CHA2DS2-VASc and ATRIA scores, including those with a CHA2DS2-VASc scores of 0-2. The authors concluded that the biomarker-based ABC score should be considered a superior tool for decisions regarding anticoagulant use in AF.

COMMENTARY

It was hard enough to remember what CHADS2 stood for, and then the newer and better CHA2DS2-VASc came along. So if for no other reason, this new ABC score is much easier to remember; however, it is not a simple 1-2 points each, add them up kind of score. It is a complicated nomogram that cannot be stored in your head unless you are some kind of savant. There is an online calculator (http://bit.ly/2jgavO1), but it only uses troponin T, so if your hospital uses troponin I, like mine does, you are out of luck. Also, the website offers a calculator for the ABC bleeding score, which has been shown to be superior to the HAS-BLED and the ORBIT-AF bleeding scores, but it requires growth differentiation factor-15 or cystatin blood levels, which are not routine tests in many laboratories, including mine.1 In addition, the ABC risk score for stroke uses NT-proBNP, and my hospital uses BNP. Thus, I can’t use either score conveniently. Perhaps in the future these, and other less common biomarkers will be available more readily as the clinical utility of so-called proteomics catches on. Analyzing DNA has been a major disappointment clinically, and current risk prediction researchers now focus on proteins. This study clearly showed that by just measuring two biomarkers, the clinical predictors of sex, hypertension, diabetes, and other cardiovascular disease no longer provide incremental value.

The strengths of this study included the large derivation and validation cohort sizes. Also, the score is well-calibrated, as the prediction of events was similar in both cohorts. The major weakness of this study is that all the patients in RE-LY and half the patients in ARISTOTLE were on anticoagulants. How do you apply the score clinically? Will it be as accurate in a population that has not been started on anticoagulants? If someone exhibits a low-risk score on anticoagulants, can you stop them? If someone demonstrates a high score on anticoagulants, do you do something else, such as left atrial exclusion? Another issue is that biomarkers can change over time. Should you calculate the score periodically and adjust treatment accordingly? Further study seems to be necessary to use the ABC score clinically. However, the authors noted that placebo-controlled trials of oral anticoagulants in AF are no longer ethical, so any new knowledge gained will be limited by this constraint. At this point, I’m going to stick with CHA2DS2-VASc until something clearly better clinically and easier to use comes along. Thank goodness for online and smartphone applications to calculate these scores.

REFERENCE

  1. Hijazi Z, Lindbäck J, Alexander JH, et al. The ABC (age, biomarkers, clinical history) stroke risk score: A biomarker-based risk score for predicting stroke in atrial fibrillation. Eur Heart J 2016;37:1582-1590.