Clinical Complexity in Atrial Fibrillation: from determinants to comprehensive and integrated management according to the ABC pathway

BACKGROUND: The epidemiology of atrial fibrillation (AF) is changing: patients with AF are increasingly older, and with more comorbidities. The interaction of different conditions (such as age, frailty, multimorbidity and polypharmacy) entails the so-called “clinical complexity”, a clinical scenario characterized by challenges in clinical management, higher risk of adverse outcomes, and complex health needs. Historically, studies have focused on the evaluation of single determinants of clinical complexity, although this approach may lack the comprehensiveness needed to investigate this condition. Moreover, clinical complexity requires integrated and holistic management to improve prognosis, and the ‘Atrial fibrillation Better Care’ (ABC) pathway has been proposed to streamline a holistic or integrated care approach for the management of patients with AF. Such approach encompasses a specific focus on the management of comorbidities and associated risk factors, and has been found effective in improving outcomes in patients with AF. AIMS: In this project, aims were 1) to evaluate clinical complexity in real-world patients with AF, according to levels and phenotypes of clinical complexity; and 2) to evaluate the effectiveness of the ABC pathway in improving outcomes in patients with AF, across different levels and phenotypes of clinical complexity. METHODS: Using data from a large, European-wide registry of patients with AF, we implemented different assessment of clinical complexity, according to a) the presence of at least one determinants among frailty, multimorbidity, polypharmacy; b) levels of complexity, as identified by a k-medoids cluster analyses based on age, frailty, number of comorbidities and number of drugs received; and c) phenotypes, evaluated through latent class analysis-defined comorbidity patterns, based on 18 chronic diseases (including cardiovascular and non-cardiovascular ones). The association of clinical complexity with major outcomes was evaluated through multiple-adjusted Cox regression analyses; a composite of all-cause death and major adverse cardiovascular events was the primary outcome for our analyses. We additionally evaluated the associations of phenotypes of complexity with use of oral anticoagulant (OAC) at baseline, and the association of the adherence to the ABC pathway (either full adherence vs. non-adherence, or adherence to 2-3 vs. 0-1 ABC criteria) on the risk of the primary outcome across different definitions of clinical complexity. RESULTS: 9,966 AF patients were included in the first analysis; of these, 83.2% were considered as clinically complex, presenting with at least one among frailty, multimorbidity, or polypharmacy; cluster analysis identified 44.5% of patients with a high clinical complexity level. At multiple-adjusted Cox-regression analysis, clinically complex patients had a higher risk of the primary outcome of all-cause death and MACE (Hazard Ratio [HR] 1.76, 95% Confidence Interval [CI] 1.36-2.28), as well as of other secondary outcomes; similar results were found when comparing patients in the high vs. moderate complexity cluster (HR 1.87, 95%CI: 1.59-2.19 for primary outcome). Adherence to the ABC pathway was associated with significant lower risk of the primary composite outcome in clinically complex patients (HR: 0.70, 95%CI: 0.58-0.85) as well as in the high complexity cluster (HR: 0.76, 95%CI: 0.60-0.96), without significant interaction observed in patients with vs. without clinical complexity (p for interaction [pint1]=0.325) and in high vs. moderate complexity cluster (pint=0.497). When we explored phenotypes of complexity, we identified 5 comorbidity patterns, with increasingly complex clinical profiles, as follows: “low-morbidity” pattern (which accounted for 46.1% of patients); “cardiovascular” pattern (25.0%) “metabolic pattern” (11.3%); “heart failure” pattern (9.7%); and a “multisystemic” pattern (8.0%). Phenotypes were heterogeneously associated with use of OAC, and showed an increased risk of major outcomes as the complexity of the clinical profile increase; highest magnitude of risk increase for the primary composite was observed in the heart failure and multisystemic patterns (HR: 2.18, 95%CI: 1.74-2.72 and HR: 2.14, 95%CI: 1.62-2.82, respectively). Adherence to the ABC pathway was associated with similar and consistent reduction in the risk of the primary outcome across phenotypes of complexity (pint=0.885); conversely, adherence to 2-3 vs. 0-1 ABC criteria was associated with highest magnitude of risk reduction in the metabolic and multisystemic patterns (pint=0.011) CONCLUSIONS: Clinical complexity is common in patients with AF, and is heterogeneously associated with clinical management and prognosis. Evaluation of clinical complexity through integration of different determinants and comorbidities and their interplay may offer a promising approach for its assessment in research and real-world practice. An integrated and holistic approach, such as the ABC pathway, is associated with improved prognosis in clinically complex patients with AF, representing a pragmatic and effective intervention to address the increasingly complex health needs of these patients.