Atrial Fibrillation and Anticoagulation: One Size Fits All?

In today's medical practice, stroke and thromboembolism are naturally associated with atrial fibrillation (AF), which was accepted nearly 70 years ago as a predictor of stroke for patients with advanced rheumatic valvular heart disease (1). However, AF in the absence of significant valvular heart disease was not universally accepted as a stroke risk factor until data from the Framingham Heart Study showed an independent association between AF and stroke (2, 3). This outcome discrepancy of early trials was attributed to the relative ages of the different patient populations studied. In Framingham, older patients with AF had a higher stroke risk (1.5% for persons aged 50 to 59 years vs. 23.5% for those aged 80 to 89 years) (4). Thus, early studies raised the possibility that AF stroke risk (in this example, age) depends on the population studied. Research then focused on approaches to preventing stroke and thromboembolism in patients with AF, and data consistently showed the efficacy of anticoagulation for stroke risk reduction (5). The focus also moved to tools for predicting which patients would benefit from anticoagulation, and from this emerged the stroke risk algorithms CHADS2 and CHA2DS2-VASc (congestive heart failure; hypertension; age; diabetes mellitus; stroke, TIA, or thromboembolism; sex; and vascular disease), which were designed to better determine anticoagulation candidacy (6). Many studies confirmed the usefulness of the CHA2DS2-VASc score, although the populations were predominantly of European origin and some populations may not follow the CHA2DS2-VASc scheme precisely (7). Asians, for example, may benefit from decreasing the age cutoff for stroke risk. Recent data suggest that lowering the cutoff to 50 years, such that an age range of 50 to 65 years derives 1 point in a modified CHA2DS2-VASc score, may better predict stroke risk in an Asian population (8). Current society guidelines recommend anticoagulation at a CHA2DS2-VASc score of 2 or higher and consideration of anticoagulation at a score of 1 or higher (9). In the present study, Shah and colleagues (10) show vulnerability in the assumption of a universal net benefit (or risk) of anticoagulation for a specific CHA2DS2-VASc score. By applying analytic models of the CHA2DS2-VASc scheme to 4 cohorts of patients, they found variability in the overall benefit of anticoagulation for a specific CHA2DS2-VASc value. Of note, each of the 4 cohorts generated distinct thresholds, such that anticoagulation would provide the best benefit at scores of at least 0 for the Danish National Patient Registry cohort, at least 1 for the SPORTIF (Stroke Prevention using ORal Thrombin Inhibitor in atrial Fibrillation) study population, at least 2 for the Swedish AF cohort, or at least 3 for the ATRIA (AnTicoagulation and Risk Factors In Atrial Fibrillation) participants. These results question the optimal CHA2DS2-VASc cutoff for starting anticoagulation for a given population or even a specific patient. Thus, this report by Shah and colleagues demonstrates one of the ways in which treatment of patients with AF cannot be assumed to be equal across different populations and shows that the CHA2DS2-VASc score threshold for anticoagulation may be not a one-size-fits-all approach but rather a starting point for a more tailored assessment. A risk calculator like the CHA2DS2-VASc algorithm, which uses fixed whole integers, may lack adequate sensitivity and flexibility for its components. For example, female sex now seems to be a risk modifier, and its intensity depends on other risk factors. Nonetheless, the CHA2DS2-VASc score remains the leading approach to assessing AF risk and the benefit of anticoagulation, and further improvements may be expected. When it comes to the conversation about the risks and benefits of anticoagulation for our patients with AF, we must remember that each patient is an individual and has his or her own score.