Screening for Atrial Fibrillation in Relation to Stroke and Mortality Risk

Abstract

Risk of Ischemic Stroke in Asymptomatic Atrial Fibrillation Incidentally Detected in Primary Care Compared with Other Clinical Presentations There has been much advocacy for the implementation of screening strategies for asymptomatic atrial fibrillation (AF),[1] given the high health care burden associated with this common arrhythmia.[2] Importantly, AF can occur asymptomatically in up to 40% of the cases, even though no profound differences were reported between symptomatic and asymptomatic AF patients in terms of risk for adverse outcomes.[3] [4] Based on this evidence, implementing screening strategies to effectively identify unknown AF patients has highlighted how structured screening strategies are effective in identifying a higher number of high-risk AF patients needing the prescription of oral anticoagulants (OACs), and that using such strategies to increase OAC can be cost-effective.[5] [6] [7] Notwithstanding this, most of the studies reported thus far have only focused on the diagnostic yield related to the screening procedure and were not designed or powered to identify a significant clinical benefit in reducing adverse events in screened patients compared with those incidentally diagnosed with AF.[1] On the basis of this lack of evidence, in 2018 the United States Preventive Services Task Force (USPSTF) released a statement which still did not recommend the use of large-scale systematic screening strategies to identify AF patients.[8] [9] In this issue of Thrombosis and Haemostasis, Wallenhorst and colleagues present an interesting and topical analysis[10] derived from the United Kingdom Clinical Practice Research Datalink, linked to the Hospital Episodes Statistics and the Office for National Statistics to gather information regarding hospital admissions and mortality data. In this analysis using International Classification of Diseases-10th Revision codes, the authors analyzed 22,035 adult (18–84 years old) subjects with incident AF from January 1, 2001 to October 31, 2009 categorized according to the mode of AF detection. Hence, the patients were divided as follows: (1) asymptomatic incidentally detected ambulatory AF (AA-AF) [N = 5,409, 24.5%)]; (2) symptomatic ambulatory AF (SA-AF) [N = 5,913, 26.8%]; (3) AF as primary hospital discharge diagnosis (PH-AF) [N = 4,989, 22.6%); (4) AF as nonprimary hospital discharge diagnosis (Non-PH-AF) [N = 26.0%]. The study cohort was then analyzed and compared with 23,605 non-AF matched patients, regarding the occurrence of stroke and all-cause death during long-term follow-up. At baseline, AA-AF patients were found to be less affected by comorbidities, with an overall low thromboembolic risk, similarly to non-AF patients. Conversely, the non-PH-AF group showed the highest burden of comorbidities and the highest level of thromboembolic risk. SA-AF and PH-AF patients showed a mixed clinical profile being both moderately comorbid, but with PH-AF ones being younger and with the lowest thromboembolic risk. Over a 3-year follow-up, while the non-AF group was associated to lower risk of stroke occurrence, in a fully adjusted competitive risk analysis compared with the AA-AF group, all the other three groups (SA-AF, PH-AF, and Non-PH-AF) reported no differences in the association with stroke events, as compared with the asymptomatic patients.[10] Similar results were found when restricting the observation to high-risk patients only (males with CHA₂DS₂-VASc ≥2 and females with CHA₂DS₂-VASc ≥3). Non-AF subjects were associated with a lower risk and the SA-AF and PH-AF ones showed no difference in association with all-cause death; however, non-PH-AF patients were associated with a higher risk of all-cause death compared with asymptomatic patients. Notably, the rate of OAC prescription was generally low (∼29%), with no differences between low- and high-risk patients and both AA-AF and SA-AF having the same OAC prevalence, while non-PH-AF subjects were markedly less treated with OAC (∼20%). This article allows us to highlight several important considerations regarding the modern management of AF patients. First, even in an unselected real-world cohort of subjects with first diagnosed AF, the proportion of patients with completely asymptomatic AF, which were only incidentally diagnosed, remains quite consistent, being around one-quarter of the entire study cohort. Even though those patients appeared to be slightly less burdened with comorbidities, they still have an important thromboembolic risk with more than 70% with a CHA₂DS₂-VASc score ≥2. Indeed, stroke risk changes with aging and incident comorbidities[11] [12] and the burden of symptoms does not necessarily influence the risk of outcomes, even in those who never have been symptomatic[4]; hence, asymptomatic AF patients should not be less intensively treated in comparison with symptomatic subjects.[3] Second, no differences in the risks of ischemic stroke between asymptomatic presentation of AF and other presentations have important clinical correlates regarding the application of opportunistic and/or systematic screening procedures in the general population. Indeed, those 5,409 asymptomatic patients who were found to be in AF were only accidentally diagnosed, mimicking what could be obtained by using an opportunistic screening applied to the entire population. If such patients had not been found in AF, none of them could have been prescribed with OAC and then an even larger number of strokes would have been recorded. In the 2020 European Society of Cardiology (ESC) clinical guidelines, the need for screening has been strongly emphasized.[13] Notwithstanding this, the ESC guidelines still recommend the use of opportunistic screening only in patients age ≥65 years, even though with a “B” level of evidence, while the use of systematic screening is suggested to be considered in subjects...