Atrial fibrillation (AF), which is a highly prevalent arrhythmia, has contributed to substantial cardiovascular death and cardiac morbidity from AF-related complications (1). Indeed, AF is associated with higher all-cause mortality (4.6% per year), only 10% of death is caused by stroke and nearly 50–60% attribute to other cardiovascular events (2, 3). Hence a comprehensive and integrated care method to management of AF and its associated comorbidities has been proposed to reduce these adverse outcomes (4, 5).

The Atrial fibrillation Better Care (ABC) pathway was introduced as an method to streamline the integrated or holistic management of AF (6). The ABC pathway has three main components: “A” refers to Avoid stroke with Anticoagulation, which means. optimizing stroke prevention with oral anticoagulation (OAC); “B” involves Better symptom management,i.e. improvement on symptom with rate or rhythm control by patient-centered symptom directed decisions; “C” applies to Cardiovascular risk factor and other Concomitant diseases management, including lifestyle modification (6).

Several studies have shown that the ABC pathway compliant management could reducing risk of adverse events (7–12) and this integrated pathway approach has also been recommended by 2020 ESC AF guidelines (13). Nonetheless, relatively few studies have investigated the impact of ABC pathway compliance in Asian countries, with the evidence derived from one cluster randomized trial (14) and one cohort study from Korea (9).

In China, nearly 7.9 million (about 2%) people suffer from atrial fibrillation (15). In addition, the anticoagulated rate and comorbidities control rate are quite low (6 and 4% respectively) (15, 16), thus comprehensive management seems to be urgent for Chinese population. However, the beneficial evidence of this kind of pathway remains limited in Chinese population. In this analysis derived from the Chinese Atrial Fibrillation registry (CAFR) dataset, we investigated if ABC pathway compliance is associated with reduced adverse events in a large Chinese cohort consisting of AF patients.

This retrospective analysis was based on the Chinese Atrial Fibrillation registry (CAFR), which is the largest, observational, prospective, register of AF patients in China. Detailed introduction about CAFR has been previously published (17). In short, the CAFR dataset has consecutively enrolled patients with AF from 31 tertiary and non-tertiary hospitals in Beijing, China, with regular follow-up of every 6 months for these patients. Pivotal data including demographic information, symptoms and signs related to AF, other comorbidities and related medication or procedures, physical examination and biochemical test results will be collected at baseline. Severe adverse events comprising the occurrence of death and other cardiovascular diseases will also be collected at each 6 month by specialized follow-up team and adjudicated by professional endpoints committee.

Patients who were older than 18 years and diagnosed by AF episode of more than 30 second documented by 12-lead electrocardiogram were qualified for inclusion. Exclusion criteria were listed as follows: (1) valvular AF, including any mechanical bioprosthetic valves, or moderate to severe mitral stenosis, (2) those who had no baseline data up to 6 months before enrollment, and (3) those who had missing data such as European Heart Rhythm Association (EHRA) symptom score. After all these selection procedures, we enrolled non-valvular AF patients amount to 19,187 in this ancillary study to confirm the beneficial evidence of the ABC compliance on clinical events of AF patients.

The ethics committees of Beijing Anzhen Hospital has approved CAFR study and all patients involved in this study were informed about the detailed information and signed up for participating consent form.

Among 19,187 patients enrolled in this study from CAFR dataset, 22.8% (n = 4,365) was defined as “ABC compliance group” and 77.2% (n = 14,822) was identified as “Non-ABC compliance group”. Baseline characteristic of these two groups were presented in Table 1.

In comparison with non-ABC compliance group, the ABC compliance group were older (62.4 ± 11.5 vs. 64.7 ± 12.1, p < 0.001), less likely to be female (34.3 vs.38.7% p < 0.001) and had a lower systolic blood pressure (120.0 ± 10.2 vs. 130.5 ± 17.5, p < 0.001). The AF type in the ABC group was less likely to be new onset and paroxysmal AF. The ABC group also had a lower prevalence of comorbidities, including coronary artery disease, peripheral arterial disease, hypertension, heart failure, ischemic stroke or TIA, diabetes mellitus and chronic kidney disease (eGFR < 60), and were treated with less drugs.

As expected, the ABC group had a lower mean CHA₂DS₂-VASc score (1.8 ± 1.3 vs. 2.7 ± 1.9, p < 0.001) and HAS-BLED score (1.5 ± 0.9 vs. 1.9 ± 1.2, p < 0.001) than the Non-ABC group. There was a borderline significant difference in the proportion of catheter ablation use between these two groups (p = 0.0506).

In this report from the CAFR Registry, we present novel data from a large observational cohort of Chinese AF patients, whereby clinical practice compliant with the ABC integrated care was associated with a significant lower risk in all-cause mortality and composite outcome of all-cause death, ischemic stroke and intracranial hemorrhage. Moreover, with more components of ABC pathway criteria fulfilled, the risk of all-cause mortality and composite outcome was progressively lower.

The favorable impact resulting from comprehensive care and integrated method to AF management is reported in a randomized control trial and various real-world evidence studies (18, 19), although relatively limited data come from large Asian cohorts. The ABC pathway, which provides a simple, effective, and easily operationalizable integrated pr holistic AF management for patients and their carers, satisfies these demand and was recommended by the 2020 European Society of Cardiology guidelines (13).

Previous studies have shown that therapies compliant with the holistic care (ABC compliance group) were associated with a significantly lower all-cause death and the composite outcome consisting of cardiovascular motality, myocardial infarction, ischemic stroke, total hospitalizations and major bleeding, compared with non-ABC compliant group (7–12). Also, a system review and a meta-analysis have revealed an obvious risk reduction in ABC group despite the variation including population selection, definition of ABC and clinical outcomes among these studies (20, 21). Our findings are consistent with the foregoing studies presenting lower hazard of all-cause death and the composite outcome in patients compliant with ABC care in comparsion to those without ABC pathway. The result that the risk of all-cause mortality and composite outcome was progressively lower with more components of ABC pathway criteria fulfilled was also found in other similar studies, which further points to an important lesson that a larger clinical benefit would accrue to those who were increasingly adherent to the ABC pathway management (7, 9, 10).

In our study, Cox regression did not present a significant lower risk in ischemic stroke and intracranial hemorrhage, and the similar result was also reported in other studies, including a recent randomized controlled trial (7, 10, 14). We hypothesized that these results may be caused by the relatively low incidence of stroke and intracranial hemorrhage events compared with other cohort studies, and the poor control of anticoagulation observed from Asian cohorts (22, 23) as nearly 50% of AF patients were prescribed warfarin in our study.

As the original cohort, from which the data were derived, represents the largest observational study for AF management in China, the results we presented are indicative of contemporary AF management nationwide in comparsion to previous studies exploring the beneficial evidence of ABC compliance approach that confined in limited cohorts, or those which were involved with patients from other countries (7–9). Moreover, this cohort comprises of the largest number of patients with ABC compliance management, presenting reliable results in relation to the amount of patients and events.

As an observational study, there are some limitations to be considered. Almost half of AF patients using warfarin in this cohort, and the lack of TTR data remains the efficiency of anticoagulation unknown, leading to some bias of the correlation of ABC adherent care and clinical outcomes. Even though the multivariable COX regression analysis presented an significant association between ABC compliance and reduced risk of these adverse events, some other related factors were not involved, including the presence of other concomitant diseases not available at baseline in this study or mentioned as part of the “C” criterion. Also, we have limited information on individual adherence and persistence to medication as well as the lack of a formalized approach to the evaluation of pharmacological treatment.

Finally, given the nature of the observational study, our data could only describe associations rather than demonstrate causality. Even if a large number of covariates have been adjusted in the the multivariable analysis, it seems to be unreasonable to make an inference of causality with the differences at baseline characteristics between the ABC group and non-ABC group. Hence, prospective studies with adequate power are needed to further confirm our findings.

In a large cohort of Chinese AF patients, ABC integrated management presents a significant association with a reduced risk for all-cause motality and composite outcome of all-cause death, ischemic stroke and intracranial hemorrhage. With higher number of the components of ABC compliance fulfilled, the risk of clinical events was progressively lower.

An increasing number of ABC criteria fulfilled was associated with a progressively lower risk of adverse clinical outcomes.

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the Ethics Committees of Beijing Anzhen Hospital. The patients/participants provided their written informed consent to participate in this study.

Y-FW wrote this paper with help of other professors, including making study design, analyzing data, and revising this article. All authors contributed to the article and approved the submitted version.

This work was supported by the National Key Research and Development Program of China (Grant Numbers: 2018YFC1312501 and 2017YFC0908803) and the National Natural Science Foundation of China (82103904). The construction of the Chinese Atrial Fibrillation Registry was also supported by grants from Bristol-Myers Squibb, Pfizer, Johnson & Johnson, Boehringer-Ingelheim, and Bayer.

C-SM has received honoraria from Bristol-Myers Squibb, Pfizer, Johnson & Johnson, Boehringer-Ingelheim, and Bayer for giving lectures. J-ZD has received honoraria from Johnson & Johnson for giving lectures. GL has served as a Consultant and Speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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