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Anticoagulation Therapy In Risky Geriatric Cardiac Patients

Anticoagulation Therapy In Risky Geriatric Cardiac Patients

In the realm of cardiovascular health, the coexistence of atrial fibrillation (AF) with heart failure (HF) presents a significant challenge for anticoagulation, particularly in the aging population. Uncertainties abound regarding treatment efficacy and patient outcomes. The All Nippon AF In the Elderly (ANAFIE) Registry, encompassing over 30,000 patients, seeks to unravel these complexities. Through meticulous observation, the study compared outcomes among elderly AF patients with and without HF, shedding light on the effectiveness of direct oral anticoagulants (DOACs) versus warfarin in navigating clinical events.



The coexistence of atrial fibrillation (AF) and heart failure (HF) represents a significant clinical challenge, particularly within the elderly demographic [1]. This dual burden complicates patient prognostication and raises questions about optimal therapeutic strategies. Direct oral anticoagulants (DOACs) have emerged as promising alternatives to traditional warfarin therapy for stroke prevention in AF patients [2]. However, their efficacy and safety in elderly individuals with concomitant HF remain uncertain, given the complex interplay of age-related comorbidities, renal impairment, and concurrent antiplatelet therapy [3].

To address these knowledge gaps, the All Nippon AF In the Elderly (ANAFIE) Registry was established as a multicenter, prospective observational study encompassing a vast cohort of over 30,000 elderly non-valvular AF patients [4]. The primary objective of the ANAFIE Registry is to compare clinical outcomes of anticoagulation over two years between AF patients with and without HF. By meticulously collecting and analyzing data on patient characteristics, treatment modalities, and incidence of clinical events, the registry aims to provide valuable insights into the real-world management of AF in the elderly population [5].

Central to the ANAFIE Registry’s objectives is the evaluation of DOACs versus warfarin in terms of their effectiveness and safety profiles in elderly AF patients with HF [6]. By examining outcomes such as stroke, systemic embolism, and bleeding events, the registry seeks to elucidate whether DOACs offer superior benefits over traditional anticoagulation therapy in this vulnerable patient population [7]. Ultimately, the findings from the ANAFIE Registry are poised to inform clinical decision-making and optimize the management of AF in elderly patients with HF. This improves prognosis and quality of life [8].



The methodology employed in the ANAFIE Registry was meticulous and aimed to ensure the reliability and integrity of the data collected. The registry enrolled patients aged 75 years and older with non-valvular atrial fibrillation (AF) who could visit outpatient clinics. Exclusion criteria encompassed recent cardiovascular events, hospitalization for heart failure (HF), or bleeding incidents within the month preceding enrollment, as well as patients with a life expectancy of less than one year. The registry adhered to ethical guidelines, including the Declaration of Helsinki and local requirements, with approval from relevant institutional review boards. Patients provided informed consent and retained the right to withdraw from the registry any time.

Diagnosis of HF was made by clinicians following established guidelines, with left ventricular systolic dysfunction documented separately. Anticoagulation therapy, whether direct oral anticoagulants (DOACs) or warfarin, was prescribed based on baseline assessments. Clinical outcomes analyzed included stroke/systemic embolism, major bleeding, HF hospitalization or cardiovascular death, cardiovascular events, cardiovascular death, all-cause death, and net clinical outcome. These outcomes were predefined and consistent with previous reports from the ANAFIE Registry. Anticoagulation events were adjudicated by blinded event evaluation committees, ensuring impartial assessment of outcomes and treatment effects. Overall, the rigorous methodology employed in the ANAFIE Registry underscores its significance as a robust platform for investigating the real-world effectiveness of anticoagulation therapy in elderly AF patients with HF.


The statistical analysis examined anticoagulation outcomes and treatment effects in elderly atrial fibrillation (AF) patients with and without heart failure (HF). The complete analysis set included enrolled patients, excluding those with protocol violations or lacking follow-up visits. Continuous variables were analyzed using t-tests or variance analysis. While categorical variables were compared using the χ2 test. Outcomes were evaluated at two (2) years post-informed consent, with the effect of oral anticoagulation therapy (OAC) analyzed based on HF history and OAC type at enrollment. Primary and secondary endpoints were assessed using Kaplan–Meier curves and expressed as rates per 100 person-years with 95% confidence intervals. The Cox proportional hazards model analyzed the risk of clinical events between DOAC and warfarin use, adjusting for various demographic and clinical factors. A sensitivity analysis using propensity score matching ensured balanced comparison groups. Statistical significance was put at a two-sided p-value <0.05. SAS Version 9.4 was used for analysis, providing robust insights into the comparative effectiveness of DOACs versus warfarin in elderly AF patients.



Patient Characteristics:

– Total enrolled patients: 33,062; after exclusions: 32,275 analyzed.

– HF group (37.5%): Higher mean age, lower systolic/diastolic blood pressure, and creatinine clearance compared to the non-HF group.

– More comorbidities were observed in the HF group. Over 90% received oral anticoagulation therapy (OAC), with DOAC use significantly higher in the non-HF group (68.5% vs. 64.2% in the HF group).

Outcomes by HF Status:

– Incidence of adverse events significantly higher in the HF group, including stroke/systemic embolism, major bleeding, HF hospitalization or cardiovascular death, cardiovascular events, cardiovascular death, all-cause death, and net clinical outcome.

– After adjustment, HF history is significantly associated with adverse outcomes, except stroke/systemic embolism or significant bleeding.

Patient Characteristics by HF and Anticoagulation Therapy:

– HF and non-HF groups divided by OAC type (DOAC, warfarin, or no OAC).

– The age is lowest in the DOAC subgroup and highest in the no OAC subgroup. Creatinine clearance was lowest in the no OAC subgroup in the HF group.

– DOAC is associated with lower risks for adverse events compared with warfarin, regardless of HF status.

Additional Analyses:

– Sensitivity analysis (propensity score matching) yielded similar results, showing DOAC associated with lower risks for adverse events than warfarin.

– Exploratory analyses based on creatinine clearance, AF type, and antiplatelet drug usage showed no significant interactions with DOAC/warfarin use for adverse events.

Overall, findings suggest that DOAC use is associated with lower risks for adverse clinical events compared with warfarin, regardless of HF status or other patient characteristics. These results underscore the potential benefits of DOAC therapy in elderly patients with non-valvular AF.



The discussion from the ANAFIE Registry sub analysis sheds light on several significant findings. Firstly, it establishes a clear association between the coexistence of heart failure (HF) and atrial fibrillation (AF) in elderly patients aged 75 years and older, emphasizing a higher risk of adverse clinical events such as HF hospitalization or cardiovascular events in this population [1].

Moreover, the study underscores the effectiveness of direct oral anticoagulants (DOACs) compared to warfarin in mitigating various adverse outcomes in elderly patients with non-valvular AF, irrespective of the presence or absence of HF. Despite potential factors such as impaired kidney function and AF type, DOACs demonstrate consistent benefits over warfarin, suggesting their favorable profile for anticoagulation therapy in this demographic [1].

The characteristics of HF patients in the study, primarily indicating HF with preserved ejection fraction (HFpEF), align with previous reports linking AF prevalence with HFpEF. Despite differences in patient demographics compared to earlier trials, the incidence rates of critical outcomes in HF patients remain consistent, affirming the robustness of the findings [1].

Furthermore, the research explores potential mechanisms underlying the association between DOAC use and HF prognosis, including lower bleeding incidence and possible benefits for preventing atherosclerosis and cardiac remodeling. However, further studies are warranted to fully explain these mechanisms and their long-term implications [1].

While the findings diverge from the ARISTOTLE study regarding apixaban’s association with HF hospitalization, discrepancies may arise from variations in study duration and patient characteristics. Overall, the study elaborates on the importance of considering HF status when evaluating anticoagulation therapy in elderly AF patients and underscores the favorable profile of DOACs in this context [1].



  1. Post Hoc Analysis:

   – The analysis was conducted post hoc rather than being prespecified.

   – This approach may introduce bias or confounding factors.

  1. Diagnosis of Heart Failure (HF):

   – HF diagnosis relied on individual investigators without access to detailed data such as echocardiography or plasma B-type natriuretic peptide levels.

   – Lack of comprehensive data may limit the precision of HF classification.

  1. Emerging Drugs Absent:

   – Emerging drugs such as angiotensin receptor-neprilysin inhibitors (ARNI) or sodium-glucose cotransporter-2 (SGLT-2) inhibitors were not utilized during the ANAFIE Registry.

   – While no apparent interactions have been reported between these drugs and oral anticoagulant therapy, their absence from the study may influence overall outcomes.

  1. Study Design and Prevalent Use of Oral Anticoagulant Therapy:

   – The study was performed using an active-comparator design.

   – Most patients received oral anticoagulant therapy at registration, reflecting prevalent use.

   – This design and prevalent use may limit the ability to establish a cause-effect relationship between direct oral anticoagulant (DOAC) use and the prevention of cardiovascular events or HF hospitalization.

  1. Need for Further Research:

   – Further research is needed to explore the relationships between DOAC use and cardiovascular outcomes, especially considering the abovementioned limitations.

These limitations underscore the need for cautious interpretation of the study findings and highlight areas for future investigation.



The study concludes that while it provides insights into the link between direct oral anticoagulant (DOAC) use and cardiovascular outcomes in elderly atrial fibrillation (AF) patients with heart failure (HF), several limitations exist. These include the post hoc analysis, reliance on investigator diagnoses of HF without detailed data, absence of emerging drugs like angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and the prevalent use of oral anticoagulant therapy. These limitations emphasize the need for a cautious interpretation of the findings and highlight the necessity for further research to clarify the relationship between DOAC use and cardiovascular outcomes in this population.



  1. [1] Kazemian P, Oudit G, Jugdutt BI. Atrial fibrillation and heart failure in the elderly. Heart Fail Rev. 2012; 17:597-613. (
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  5. [5] Ferreira J, Ezekowitz MD, Connolly SJ, Brueckmann M, Fraessdorf M, Reilly PA, et al. Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: A subgroup analysis of the RE-LY trial. Eur J Heart Fail. 2013; 15:1053-1061. (
  6. [6] Marinigh R, Lip GYH, Fiotti N, Giansante C, Lane DA. Age as a risk factor for stroke in atrial fibrillation patients: Implications for thromboprophylaxis. J Am Coll Cardiol. 2010; 56:827-837. (
  7. [7] Krittayaphong R, Boonyapiphat T, Wongvipaporn C, Sairat P. Age-related clinical outcomes of patients with non-valvular atrial fibrillation: Insights from the COOL-AF registry. Clin Interv Aging. 2021; 16:707-719. (
  8. [8] López-López JA, Sterne JAC, Thom HHZ, Higgins JPT, Hingorani AD, Okoli GN, et al. Oral anticoagulants for stroke prevention in atrial fibrillation: Systematic review, network meta-analysis, and cost-effectiveness analysis. BMJ. 2017; 359:j5058. (
  9. [1] Ikeda S, Takayama M, Sakagami S, et al. Clinical outcomes and anticoagulation therapy in elderly non-valvular atrial fibrillation and heart failure patients. ESC Heart Fail. 2023. (


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