Integrated Care for Atrial Fibrillation Using the ABC Pathway in the Prospective APHRS-AF Registry

Background The Atrial Fibrillation Better Care (ABC) has been proposed as an integrated approach to improve management in patients with atrial fibrillation (AF), based on 3 pillars: “A” Avoid stroke with Anticoagulation; “B” Better symptoms control; “C” Cardiovascular risk-factor and comorbidities management. Objectives This study sought to investigate the association with outcomes of ABC adherence in the prospective multinational Asia-Pacific Heart Rhythm Society (APHRS) Atrial Fibrillation registry. Method Cox-regression analyses adjusted for age, sex, CHA2DS2-VASc score, paroxysmal AF, chronic obstructive pulmonary disease, chronic kidney disease, cancer, dyslipidemia, and dementia were performed to investigate the association with outcomes. Primary outcome was a composite of all-cause death, any thromboembolic events, acute coronary syndrome or percutaneous interventional procedures, and advancing heart failure. Results Of the 4,013 included patients with AF (mean age 68 ± 12 years; 34.4% female); 38.6% were adherent to all 3 main ABC pillars. After 1 year of follow-up, adherence to the ABC pathway was associated with a low incidence of composite outcome (4.0% vs 8.5%, P < 0.001), all-cause and cardiovascular death, and advancing heart failure. On Cox regression analysis, ABC adherence was associated with a lower risk of primary outcome (HR: 0.72; 95% CI: 0.53-0.97), with risk reduction progressively higher with a higher number of ABC criteria attained. No significant interaction in the association was seen according to the different geographic areas (Pint = 0.217). Conclusions In a large contemporary cohort of Asian patients with AF, adherence to ABC pathway was associated with a reduction of the risk for adverse outcomes. (Clinical Survey on the Stroke Prevention in Atrial Fibrillation in Asia (AF-Registry; NCT04807049)

A trial fibrillation (AF) is the most common arrhythmia worldwide and is associated with increased morbidity and mortality. 1 However, despite oral anticoagulation (OAC) with vitamin-K antagonists (VKAs) or direct-acting oral anticoagulants (DOACs) showing a significant survival improvement in patients with AF, 2 almost 70% of the causes of cardiovascular deaths in AF are not linked to thromboembolic events (TEs). 3,4 Indeed, in the ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) study on 14,171 patients with AF, after a median follow-up of 1.9 years, <10% of the cardiovascular deaths were associated with ischemic stroke or systemic embolism, 3 whereas, in a French cohort of 8,962 patients with AF, after a median follow-up of 1.3 years, only 7% of deaths were caused by stroke. 4 These was further confirmed in 4,664 Asian patients with AF enrolled in the Asia-Pacific Heart Rhythm Society (APHRS) AF registry in which, after 1 year of follow-up, ischemic stroke was associated only with 1% of the reported deaths. 5 AF often coexists with other cardiovascular comorbidities, such as arterial hypertension, heart failure (HF), diabetes mellitus, peripheral (PAD), and coronary artery disease (CAD), 6 as well as with an overall high burden of multimorbidity. 7 The presence of multiple comorbidities in patients with AF requires more comprehensive clinical management not only based on OAC therapy but also on the optimal control of all the cardiovascular risk factors and comorbidities. 8 Growing evidence shows that a holistic-care approach effectively reduces the residual risk of death and cardiovascular events (CVEs) in different AF populations. [9][10][11][12][13][14][15][16] The ABC (Atrial fibrillation Better Care) pathway was proposed to help facilitate holistic or integrated care management for patients with AF. 2 The ABC pathway has 3 main pillars: "A" for avoiding stroke with appropriate prescription of OAC; "B" refers to better symptoms optimization with patientcentered symptom-directed decisions on rate and rhythm control; and "C" for optimal management of cardiovascular and management of noncardiovascular risk factors and comorbidities, including lifestyle factors. 2 Despite several studies derived from Western populations that have already demonstrated its usefulness in reducing the risk of CVEs in patients with AF, there are relatively few prospective data on the management and treatment of patients with AF with the ABC pathway in Asian-Pacific countries. [11][12][13] Since 2015, in collaboration with the European Society of Cardiology (ESC), the APHRS created the first pan-Asian prospective AF registry, enrolling patients from 5 major Asian countries (Hong Kong, South Korea, Japan, Singapore, and Taiwan) to systematically collect contemporary data regarding the management and treatment of AF. 17 In the present study, we evaluated if clinical management adherent to the ABC pathway would be associated with a reduction in adverse outcomes in this large Asian-Pacific prospective cohort of patients with AF.   for diabetes mellitus, treatment with insulin or oral antidiabetic agents. All patients with $1 clinical condition not properly treated were considered to be "C"" criterion nonadherent. Patients were considered treated as adherent to the ABC pathway if they were adherent to all 3 criteria. We also considered adherence to only 0, 1, 2, or 3 ABC pathway criteria. All patients with at least 1 ABC criterion not attained were considered to be ABC nonadherent. were ABC nonadherent and 1,549 (38.6%) ABC adherent. As reported in Table 1, ABC nonadherent patients were older and had higher CHA 2 DS 2 -VASc and HAS-BLED scores than ABC-adherent patients.

METHODS
Overall, 3,502 patients (87.2%) were adherent to the "A" criterion; 3,756 (93.6%) were adherent to the "B" criterion; and 1,866 (46.5%) were adherent to the "C" criterion. The number of patients with 0, 1, 2, or 3 criteria attained is reported in Figure 2.   Table 2) as well as associated with a progressively lower risk according to a progressively  Table 3). Repeating this analysis, using as reference the group of patients with 0 or 1 criterion attained, we confirmed again that a higher number of criteria attained was associated with a progressively lower risk of the composite outcome (HR: 0.63; 95% CI: 0.45-0.87 and HR: 0.47; 95% CI: 0.31-0.71, respectively, for 2 and 3 criteria attained) (Supplemental Table 3). SUBGROUP ANALYSIS. Adherence to ABC was associated with a lower risk of the composite outcome irrespective of the origin country ( Figure 4). Similarly, no difference was found in the association between adherence to the ABC pathway and risk of composite outcome according to the clinical subgroups examined ( Figure 4).

DISCUSSION
In this prospective cohort of Asian patients with AF derived from the APHRS Registry, we found that 38.6% of patients showed a full adherence to the ABC pathway management, as they were complying with all 3 main pillars of this integrated approach. Second, ABC pathway adherence was associated with a 28% lower risk of a composite outcome of all-cause death and CVEs, and the risk reduction was proportionally higher according to a higher number of ABC criteria.
Third, the association between ABC pathway adherence and lower risk of outcomes was found irrespective of the enrolling country, age, sex, and AF type.  [11][12][13] These differences in ABC pathway prevalence could be due to the differences in the study design and the characteristics of the patients enrolled.
Indeed, although patients enrolled in the ChiOTEAF Registry had similar mean age and even higher CHA 2 DS 2 -VASc scores, 13 those enrolled in the other 2 studies were largely unselected patients, with lower mean age and lower baseline thromboembolic risk. 11,12 Conversely, the prevalence of ABC pathway adherence in our cohort was significantly higher when compared with that reported in a recent metaanalysis (21%). 22 Of note, the latter meta-analysis was based mainly on non-Asian studies, with higher mean age and baseline thromboembolic risk.
Moreover, we found that in the APHRS Registry, the prevalence of ABC criteria attained was 0.5% for 0 criteria, 10.2% for 1 criterion, 50.7% for 2 criteria, and 38.6% for 3 criteria: a prevalence similar to that reported in the ChiOTEAF registry. 12 Despite that in our population, adherence for "A" and "B" criteria was approximately 90%, showing good use of OAC and control of symptoms, we found that the "C" criteria were attained in <50% of patients, significantly affecting the overall prevalence of adherence to the ABC pathway. Values are mean AE SD or n (%).

FIGURE 3 Risk for Primary and Secondary Outcomes on Cox-Regression Univariate Analysis
On univariate Cox-regression analysis, ABC-adherent patients showed a lower risk of the composite outcome, all-cause death, and cardiovascular death. No significant associations were found between ABC adherence and the risk of thromboembolism, ACS/PCI, advancing HF, and major bleeding. ACS/PCI ¼ acute coronary syndrome/percutaneous coronary intervention; HF ¼ heart failure.

FIGURE 2 ABC Criteria Adherence and Distribution
The ABC pathway has 3 main pillars: "A" for avoiding stroke with oral anticoagulation; "B" refers to symptom control; and "C" for management of cardiovascular risk factors. The patient was considered compliant for the "A" criterion if properly prescribed with oral anticoagulation according to the CHA 2 DS 2 -VASc score. Any patient with no symptoms or with mild symptoms not affecting daily life was qualified for the "B" criterion. A patient was considered adherent to the "C"" criterion when hypertension, coronary artery disease, peripheral artery disease, heart failure, stroke or transient ischemic attack, and diabetes mellitus were treated according to the current clinical guidelines. All patients with $1 clinical condition not properly treated were considered to be "C"" criterion nonadherent. Patients were considered treated as adherent to the ABC pathway if they were adherent to all 3 ABC pillars.
Bucci et al AF is a clinical condition that often coexists with several diseases that increase the global risk of death and CVEs. 6 The importance of treating these clinical conditions with the optimal therapies is underlined by the risk reduction of 28% for the composite outcome that we found in our study among those patients who were ABC-pathway adherent. This result is similar to that found in previous studies performed in Asian populations that reported a risk reduction for similar composite outcomes between 24% and 49% 11-13 but is lower than the 40% to 60% risk reduction reported in studies performed in Western countries with higher ABC pathway adherence. 9,10, [14][15][16] In our analysis, the lower risk for the composite outcome in the ABC-adherent group seems to be  attaining the "C" criteria and the risk of clinical outcomes at 1-year follow-up. Other possible confounding factors, such as smoking habits; physical activity; alcohol consumption; cognitive function; and the optimal management of chronic obstructive pulmonary disease, chronic kidney disease, and dyslipidemia were not considered in this analysis, as specific data about the treatment of these conditions were not collected in the original case report form.

CONCLUSIONS
In a large contemporary cohort of Asian patients with AF, ABC pathway adherence was associated with a reduction of the risk for the composite outcome of all-cause death and CVEs. The beneficial effect of this integrated approach was found irrespective of enrolling country and various clinical characteristics.

FIGURE 4 Risk of Composite Outcome in Different Subgroups
On Cox regression multivariate analysis adjusted for age, sex, CHA 2 DS 2 -VASc, paroxysmal-AF, chronic obstructive pulmonary disease, chronic kidney disease, cancer, dyslipidemia, and dementia, full adherence to the ABC pathway was associated with a lower risk of the composite outcome irrespective of the origin country, age >75 years, sex, and AF type. AF ¼ atrial fibrillation.