Next Article in Journal
Obesity-Induced PVAT Dysfunction and Atherosclerosis Development: The Role of GHSR-1a in Increased Macrophage Infiltration and Adipocytokine Secretion
Next Article in Special Issue
Wearable Devices for Quantifying Atrial Fibrillation Burden: A Systematic Review and Bayesian Meta-Analysis
Previous Article in Journal
Predictive Threshold Value of the Breathing Reserve for the Decline in Cardiorespiratory Fitness Among the Healthy Middle-Aged Population
Previous Article in Special Issue
Atrial Fibrillation Prediction Model Following Aortic Valve Replacement Surgery
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Oral Anticoagulation Choice and Dosage in Very Elderly Patients with Atrial Fibrillation

by
Martha Zergioti
1,†,
Melina Kyriakou
1,†,
Andreas S. Papazoglou
1,
Anastasios Kartas
1,
Dimitrios V. Moysidis
2,
Athanasios Samaras
3,
Efstratios Karagiannidis
2,
Vasileios Kamperidis
1,4,
Antonios Ziakas
1,4 and
George Giannakoulas
1,4,*
1
Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
2
424 General Hospital of Thessaloniki, 56429 Thessaloniki, Greece
3
Second Department of Cardiology, Hippokration Hospital of Thessaloniki, 54643 Thessaloniki, Greece
4
First Department of Cardiology, AHEPA University Hospital of Thessaloniki, 54636 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Cardiovasc. Dev. Dis. 2025, 12(3), 86; https://doi.org/10.3390/jcdd12030086
Submission received: 18 January 2025 / Revised: 13 February 2025 / Accepted: 22 February 2025 / Published: 26 February 2025

Abstract

:
Background: Selecting the optimal oral anticoagulation (OAC) therapy for elderly patients with atrial fibrillation (AF) remains challenging. Our real-world study investigates clinical factors guiding OAC prescription patterns and compares outcomes between full- and reduced-dose direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in this demographic. Methods: This post hoc analysis of the MISOAC-AF trial focused on hospitalized AF patients aged ≥ 75 years prescribed OAC at discharge. Predictors of VKA and reduced DOAC dosing were identified using adjusted odds ratios (aORs). Cox regression models calculated adjusted hazard ratios (aHRs) for primary (all-cause mortality) and secondary outcomes (stroke, bleeding, AF or heart failure hospitalization, cardiovascular death). Results: Among 450 elderly patients, 63.6% received DOACs and 36.4% received VKAs. Higher CHA2DS2-VASc and HAS-BLED scores and antiplatelet use predicted VKA prescription. Hypertension, prior stroke, and bleeding history favored DOAC use. Advanced age and chronic kidney disease correlated with reduced DOAC dosing. Over a 3.7-year follow-up period, there was no significant difference in all-cause mortality between the DOAC and VKA groups (aHR 0.79, 95% CI 0.58–1.06) or between the full-dose and reduced-dose DOAC groups (aHR 0.96, 95% CI 0.60–1.53). Secondary analyses also did not yield statistically significant results in either comparison. Conclusions: Clinical profile parameters in elderly AF patients predict VKA or DOAC use. Clinical outcomes were similar between different OAC therapies.

1. Introduction

Atrial fibrillation (AF) represents the most prevalent form of arrhythmia worldwide, with its incidence escalating notably with advancing age [1]. In adults aged 20 or older, AF prevalence is only 3%, whereas in populations aged 75 or older, it is 9–11%, with further escalation when other cardiac comorbidities exist [2]. Projections suggest that over the forthcoming decade, AF is poised to affect between 14 and 17 million individuals within the European Union [3]. This relative increase is primarily attributed to demographic shifts characterized by an aging population, alongside enhanced detection capabilities and the exacerbating influence of predisposing health conditions such as diabetes mellitus (DM) and hypertension [4].
Over the last decades, direct-acting oral anticoagulants (DOACs) have revolutionized the therapeutic landscape for AF [5]. Since 2016, they have emerged as the preferred first-line oral anticoagulation (OAC) strategy owing to their demonstrated net clinical superiority over vitamin K antagonists (VKAs) [6]. Given the constant aging of the global population and the increasing prevalence of AF in elderly and very elderly populations, it becomes imperative to discern the optimal OAC strategy for these subgroups [7]. Currently, a substantial proportion of elderly AF patients receive suboptimal anticoagulation therapy, primarily due to concerns regarding bleeding risk (attributable to factors such as low body weight, impaired renal function, and frailty), as well as the presence of cardiac or extra-cardiac comorbidities, and non-adherence to therapy [8,9,10].
Consequently, an expanding body of literature endeavors to evaluate OAC and dosage-related outcomes in very elderly AF patients, who are often excluded from clinical trials [10,11,12,13,14,15]. The primary objective of our real-world cohort study, conducted on AF patients enrolled between December 2015 and June 2018, was to provide a succinct overview of OAC-related decision-making in AF patients aged 75 years and older, as observed at discharge by cardiologists in a tertiary hospital, reflecting the clinical practices of that era. Furthermore, our study seeks to contribute to the existing evidence base by addressing the pivotal question of whether full- or reduced-dose DOACs or VKAs offer superior clinical outcomes in the very elderly AF population.

2. Materials and Methods

2.1. Study Design and Study Population

This study constitutes a retrospective post hoc analysis of the MISOAC-AF randomized trial (Motivational Interviewing to Support Oral Anticoagulation adherence in patients with non-valvular Atrial Fibrillation, ClinicalTrials.gov identifier: NCT02941978) [16]. In brief, the MISOAC-AF trial randomized a diverse cohort of 1140 hospitalized AF patients into two groups, exploring the impact of patient–physician interviews and scripted guidance on adherence to OACs. The trial outcomes have been previously published [17]. The study adhered to the World Medical Association Declaration of Helsinki and received approval from the Bioethics Committee of the Aristotle University of Thessaloniki (protocol code: 173, date of approval: 30 November 2015). Each participant provided written informed consent before participating in the study.
In this particular investigation, we included only the subset of AF patients aged 75 and above, defined as a very elderly group of patients. Individuals with incomplete data regarding their discharge OAC regimen and those not receiving any OACs were excluded from the analysis. The included patients were categorized based on the OAC treatment at discharge, namely VKA (acenocoumarol) and DOACs (dabigatran, rivaroxaban, or apixaban). A full DOAC dose was deemed to be one comprising 150 mg dabigatran, 20 mg rivaroxaban, and 5 mg apixaban, while a reduced DOAC dose comprised 110 mg dabigatran, 15 mg rivaroxaban, and 2.5 mg apixaban.

2.2. Study Endpoints

The primary endpoint of the study was the occurrence of all-cause death during follow-up. The secondary endpoints included any stroke, major bleeding, and the composite endpoint of AF- or heart failure (HF)-related hospitalization or cardiovascular death.

2.3. Definition of Covariates

AF was identified as either previously documented in the patient’s medical history or as new-onset AF observed during hospitalization. The latter was characterized by an irregular heart rhythm persisting for more than 30 s, lacking detectable P waves, as captured by a 12-lead electrocardiogram or a 24 h Holter monitor. Cardiovascular death was defined as a death related to cardiac causes or stroke. Stroke was defined as the emergence of new, focal, or global neurological dysfunction resulting from vascular injury in the brain, spinal cord, or retinal region due to infarction. Stroke criteria included a symptom duration of at least 24 h, or otherwise the presence of a clearly corresponding lesion on CT or MRI scans. Major bleeding was characterized by fatal bleeding, symptomatic hemorrhages in critical areas or organs, a reduction in hemoglobin levels by at least 2 g/dL, or the requirement of a transfusion of at least 2 units of whole blood or red cells.

2.4. Statistical Analysis

Continuous variables are presented as means with standard deviations (SDs), while categorical variables are presented as numbers with percentages. Between-group comparisons of the categorical variables were performed using the chi-square test, while the t-test was utilized for the comparison of continuous variables.
Univariate and multivariate binary logistic regression analyses were performed to identify potential predictors of VKA prescription as compared to DOACs (used as the reference category). The variables forced into the multivariate model were selected based on their clinical relevance and the univariate logistic regression outcomes (i.e., we included the variables with univariate p-value < 0.20).
Survival analyses, accompanied by time-to-event plots (Kaplan–Meier curves), were conducted for each study endpoint to compare the prognostic course of patients receiving VKAs and DOACs (full vs. reduced dose). A multivariate Cox regression hazard model was developed by incorporating variables of clinical interest or those univariately associated with each endpoint (p < 0.20) into the multivariate analysis. These variables included age, gender, body mass index (BMI), history of smoking, HF, coronary artery disease (CAD), chronic kidney disease (CKD), DM, hypertension, stroke, and the CHADS-VASc score. Sensitivity multivariate regression analyses were also performed to include as covariates the eGFR levels at discharge and the rates of anticoagulation adherence during follow-up [18]. A two-tailed significance threshold was set at a = 0.05. The statistical analysis was performed using SPSS version 25 (SPSS Inc., Chicago, IL, USA) software.

3. Results

3.1. Baseline Characteristics

A total of 450 (39.5% of the MISOAC-AF trial population) patients with AF (47.3% males) were treated with OACs and were, thereby, included in this analysis, with a mean age of 81.9 ± 4.3 years. Of them, 286 (63.6%) received a DOAC (59 dabigatran, 103 rivaroxaban, 124 apixaban), and 164 (36.4%) a VKA (acenocoumarol). Patients on DOACs had lower HAS-BLED and CHA2DS2-VASc scores than patients on VKA (p < 0.01). Higher glomerular filtration rates (GFR) were observed in the DOAC group (p = 0.02). Higher rates of prior HF and CAD were documented in the VKA group (p < 0.05).
Regarding the dose of DOACs, 190 patients (66.4% of those under DOACs) received a reduced dose. Between the two subgroups (full vs. reduced DOAC dose), there were significant differences in age, male %, BMI, creatinine, GFR, and the prevalence of peripheral artery disease, AMI, and CKD. Baseline patient characteristics according to OAC status (DOACs vs. VKA) and DOAC dose (full vs. reduced dose) are depicted in detail in Table 1 and Table 2, respectively. The subcategories of the type and dosage of OACs are depicted in Supplementary Table S1.

3.2. Prediction of OAC Discharge Prescription

The binary logistic regression analysis set for the association of baseline covariates with DOAC or VKA prescription yielded that increasing CHA2DS2-VASc score (aOR 0.69, 95% CI 0.50–0.95, p 0.02) and HAS-BLED score (aOR 0.33, 95% CI 0.23–0.48, p < 0.01) were both correlated with a higher probability of VKA prescription. Additionally, the prescription of concomitant antiplatelet medication was negatively linked with DOAC prescription (aOR 0.74, 95% CI 0.54–1.00, p 0.05). On the other hand, comorbid hypertension (aOR 4.80, 95% CI 2.30–10.00, p < 0.01), prior stroke (aOR 4.90, CI 1.80–13.44, p < 0.01), and major bleeding (aOR 2.72, 95% CI 1.26–5.88, p 0.01) were independently linked with increased likelihood of DOAC prescription. A detailed overview of these results can be found in Table 3.

3.3. Association of OAC Type (DOACs vs. VKA) with Clinical Outcomes

The primary endpoint of all-cause death occurred in 203 (45.1%) patients over a median 3.7-year follow-up period. Among the deceased patients, 113 (39.5%) received a DOAC, and 90 (54.9%) a VKA at hospital discharge (Table 4). According to the univariable survival analysis, a lower risk of all-cause death was observed in patients on DOACs (HR 0.69, 95% CI 0.51–0.88; log-rank test: p < 0.01), compared to patients on VKAs. However, after adjustment for potential confounders, the risk for all-cause death did not differ significantly between the two groups (aHR 0.79, 95% CI 0.58–1.06, p 0.12).
Moreover, incidence of bleeding and stroke were investigated as secondary endpoints along with the composite endpoint of cardiovascular mortality and any HF- or AF-related hospitalization. Both adjusted and unadjusted risks for the secondary endpoints did not differ significantly between patients under VKA and those under DOACs. A detailed overview of these endpoints is displayed in Table 4 and Figure 1. The sensitivity analysis including OAC follow-up adherence as a covariate did not alter the prognostic effects of VKA vs. DOACs (Supplementary Table S2).

3.4. Prediction of the Prescription of Full vs. Reduced DOAC Dose

In total, 190 (66.4%) study participants were administered a reduced DOAC dose and 96 (33.6%) a full DOAC dose. The prescription of a reduced DOAC dose was positively correlated with increasing age (aOR 1.09, 95% CI 1.01–1.17, p 0.03) and history of CKD (aOR 3.53, 95% CI 1.92–6.49, p < 0.01). Patients with prior AMI showed a tendency to be administered a reduced DOAC dose (aOR 3.01, 95% CI 0.92–9.88, p 0.07); however, this analysis did not reach the statistical significance threshold. A detailed overview of these results can be found in Table 5. The sensitivity analysis including eGFR levels at discharge as a covariate instead of the CKD history did not alter the significance of the remaining predictors and yielded that increasing eGFR leads to a decreased likelihood of prescription of reduced-dose DOACs (aOR 0.96, 95% CI 0.95–0.98).

3.5. Association of DOAC Dose (Full vs. Reduced) with Clinical Outcomes

Among the deceased patients, 81 received a reduced DOAC dose (43.1%) and 32 a full DOAC dose (33.7%) at hospital discharge (Table 6). According to the univariable survival analysis, there was no difference in the risk of all-cause mortality in patients receiving reduced vs. full DOAC doses (HR 1.32, 95% CI 0.88–1.99, log-rank test: p 0.12; Figure 2). This did not alter after adjustment for confounding factors (aHR 0.96, 95% CI 0.60–1.53, p 0.85).
Moreover, incidence of bleeding, stroke, and the composite endpoint of any HF- or AF-related hospitalization or cardiovascular death were investigated as secondary endpoints. Both adjusted and unadjusted analyses for those endpoints did not show significantly different risk between patients under reduced and full DOAC doses. A detailed overview of these endpoints is displayed in Table 6 and Figure 2. The sensitivity analysis including OAC follow-up adherence as a covariate did not alter the prognostic effects of a full vs. reduced DOAC dose (Supplementary Table S2).

4. Discussion

In this post hoc observational analysis derived from the MISOAC-AF randomized trial, our investigation centered on evaluating prescription patterns and clinical outcomes associated with various OAC strategies among elderly individuals aged 75 years and older with concomitant AF. The mean age of the participants enrolled in our study was 81.9 years, with a corresponding mean CHA2DS2-VASc score of 5.4, indicative of a very high-risk real-world AF population. Notably, higher CHA2DS2-VASc and HAS-BLED scores, alongside concurrent antiplatelet therapy, were observed to correlate with an augmented likelihood of VKA prescription upon discharge. Conversely, the presence of comorbidities such as hypertension, prior stroke, and major bleeding events were associated with a higher likelihood of DOAC prescription. Furthermore, advancing age and comorbid CKD emerged as independent predictors of a higher prevalence of reduced-dose DOAC prescriptions compared to full-dose regimens. However, our comparative analysis revealed similar rates of adverse cardiovascular events during follow-up when contrasting DOACs with VKAs and full-dose DOACs with reduced-dose DOACs.
Aging is known to be associated with multiple comorbidities, polypharmacy, and altered drug pharmacokinetics [19]. Furthermore, it is considered an independent risk factor for both bleeding and thromboembolic events [20]. This dual increase in bleeding and thrombotic risk in the elderly may lead clinicians to experience uncertainty regarding the optimal anticoagulation regimen. Overall, compared with warfarin, DOACs exhibit a favorable risk–benefit profile, and their efficacy and safety in elderly patients are consistent with those of the overall population [21,22,23,24]. Because DOACs have a wide therapeutic window, predictable anticoagulant effects, and few interactions with other drugs, they may be preferable to VKAs, and their prescription is recommended in the latest guidelines (Class IA, 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of AF) [25].
The primary survival analysis yielded a non-significant trend of higher mortality in patients on VKAs compared to patients on DOACs, which could be attributed to the increasing frailty and complicated status of patients on VKAs. Nevertheless, no statistical superiority of either VKAs or DOACs was proved after adjustment, and the clinical superiority of DOACs over VKAs was not confirmed in this multimorbid AF population. A comprehensive review of the latest literature reveals the safety and efficacy of DOACs as an anticoagulation regimen in the elderly. For example, the prospective multicenter START2-REGISTER study, which included AF patients aged ≥85 years, indicated a significant survival benefit in those treated with DOACs with similar bleeding risk but a higher risk for cerebral thrombotic events compared to VKAs [26]. Moreover, a Norwegian nationwide cohort study of elderly AF patients initiating thromboprophylaxis showed that both full and reduced DOAC doses were associated with similar risks of thromboembolism to those of warfarin and lower or similar risks of bleeding [27]. Subgroup analyses of the RE-LY trial [28], the ROCKET-AF trial [22], and the ARISTOTLE trial [29] also demonstrated the clinical benefit and safety of DOAC use in patients aged ≥75 years. However, a recent randomized trial (the FRAIL-AF) concluded that switching from VKAs to DOACs in frail older patients with AF was associated with more bleeding complications, without a reduction in thromboembolic complications, compared with continuing VKA treatment [30]. Nevertheless, a recent study conducted in Sichuan, China reached a different conclusion regarding elderly, frail patients with AF and highlighted the importance of DOAC therapy to reduce risk of thrombotic events; at the same time, there was no increase in fatal bleeding [31].
Choosing the appropriate dosing of DOACs is a complex question for most physicians, especially when treating elderly populations, where they must consider competing risks of stroke and bleeding, anticipated changes in renal function, interacting medications, and patient frailty to establish an appropriate starting dose. These difficulties are compounded by the exclusion or underrepresentation of the most complex cases, such as patients with severe CKD or prior intracranial bleeding, in pivotal DOAC trials. The possibility of underdosing or overdosing should also be taken into account. A recent study from the Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) investigated the degree of recommended and non-recommended dosing of DOACs among 10,426 AF patients and found that 23.2% were underdosed and 3.8% were overdosed. Interestingly, the prescription of non-recommended doses was associated with a 25% higher risk of all-cause mortality. Similarly, the PAVE-AF study (Tzeis et al.) also revealed reluctance in DOAC prescription or prescription with inappropriate dosing in elderly population; the EUROSAF study also highlighted the underuse of optimal DOAC dosing despite the preference of DOACs over VKAs, concluding that significant treatment gaps may exist, driven by multimorbidity, polypharmacy, and concerns about bleeding risks [32,33,34,35].

Limitations

The primary limitation of this study is its retrospective design. Τhe presence of unmeasured confounders that may have influenced the choice of OAC treatment in this subgroup is highly likely. While we adjusted for baseline characteristics with clinical and statistical significance, the lack of information on follow-up changes in anticoagulation treatment or INR/eGFR levels during follow-up could lead to misleading outcomes. No propensity-score matching approach was implemented in this study to reduce potential treatment selection bias. Moreover, there were no frailty indices documented to assess patient stratification and explore the role of frailty in anticoagulation decision. Furthermore, the limited sample size of this study resulted in analyses with insufficient power to assess hard clinical endpoints and prevented subgroup analyses based on DOAC type. Consequently, our findings should be considered exploratory.
The data, as they were extracted from the MISOAC-AF trial, reflect an older time period in terms of recommended anticoagulation patterns; the first enrollment and randomization took place in December 2015, and subsequent recruitment in MISOAC-AF was completed in June 2018. The timing of the study may possibly explain the non-significant trend of higher mortality observed in patients on VKAs in the univariate survival analysis. During that period, doctors tended to prescribe VKAs to patients with more complex AF, a practice that may no longer be common today. Finally, our sample size may not have been sufficient to replicate the previously reported results from other trials. It is important to highlight the small number of patients divided into either of the two subgroups (190 vs. 96 patients under the full and reduced DOAC dose, respectively) in our study. However, the lack of large randomized controlled trials comparing DOACs head-to-head at different dosages, and the difficulty of conducting future large-scale clinical trials investigating outcomes associated with different doses, should also be taken into account; such trials are hardly feasible, as deliberately underdosing or overdosing patients in a clinical trial is ethically problematic.

5. Conclusions

This observational post hoc analysis of a randomized clinical trial explored prescription patterns and clinical outcomes of OAC strategies in very elderly patients aged over 75 years with comorbid AF. The study population exhibited a high-risk profile which is indicative of a real-world AF cohort. In this population, the survival benefit of DOACs over VKAs was not confirmed. The intricacies of dosing remain a clinical conundrum, particularly in elderly populations with complex medical histories. Individualized dosing decisions should consider factors such as renal function, concurrent medications, past medical history, and frailty. Larger-scale observational studies and randomized controlled trials are needed to compare the effects of DOACs at different dosages in this clinical context.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcdd12030086/s1, Table S1: Type and dose of OAC prescribed at hospital discharge. Table S2: Sensitivity analysis outcomes after adjustment for patients’ anticoagulation adherence during follow-up.

Author Contributions

M.K., M.Z. and A.S.P. wrote the manuscript. A.K., A.S., D.V.M., E.K. and V.K. reviewed the manuscript and contributed to the data collection. A.Z. and G.G. supervised the study. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Bioethics Committee of the Medical School of the Aristotle University of Thessaloniki (protocol code: 173, date of approval: 30 November 2015).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Data are available from George Giannakoulas (e-mail: ggiannakoulas@auth.gr) upon reasonable request and with the permission of AHEPA University Hospital.

Acknowledgments

The authors thank Anastasios Papanastasiou, Eleni Vrana, Dimitra Vasdeki, George Dividis, George Fotos, Eleni Paschou, Evropi Forozidou, Paraskevi Tsoukra, Eleni Kotsi, and Ioannis Goulas for their contribution to the initial data collection of the MISOAC-AF trial.

Conflicts of Interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

List of Abbreviations

OAC: oral anticoagulation, AF: atrial fibrillation, DOACs: direct oral anticoagulants, VKAs: vitamin K antagonists, GFR: glomerular filtration rate, BMI: body mass index, HF: heart failure, CAD: coronary artery disease, CKD: chronic kidney disease, DM: diabetes mellitus, aOR: adjusted odds ratio, HR: hazard ratio, 95% CI: 95% confidence interval.

References

  1. Lippi, G.; Sanchis-Gomar, F.; Cervellin, G. Global epidemiology of atrial fibrillation: An increasing epidemic and public health challenge. Int. J. Stroke 2021, 16, 217–221. [Google Scholar] [CrossRef] [PubMed]
  2. Kannel, W.B.; Wolf, P.A.; Benjamin, E.J.; Levy, D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: Population-based estimates. Am. J. Cardiol. 1998, 82, 2N–9N. [Google Scholar] [CrossRef]
  3. Chugh, S.S.; Havmoeller, R.; Narayanan, K.; Singh, D.; Rienstra, M.; Benjamin, E.J.; Gillum, R.F.; Kim, Y.-H.; McAnulty, J.H., Jr.; Zheng, Z.-J.; et al. Worldwide epidemiology of atrial fibrillation: A Global Burden of Disease 2010 Study. Circulation 2014, 129, 837–847. [Google Scholar] [CrossRef] [PubMed]
  4. Papazoglou, A.S.; Kartas, A.; Moysidis, D.V.; Tsagkaris, C.; Papadakos, S.P.; Bekiaridou, A.; Samaras, A.; Karagiannidis, E.; Papadakis, M.; Giannakoulas, G. Glycemic control and atrial fibrillation: An intricate relationship, yet under investigation. Cardiovasc. Diabetol. 2022, 21, 39. [Google Scholar] [CrossRef]
  5. Hanon, O.; Jeandel, C.; Jouanny, P.; Paccalin, M.; Puisieux, F.; Krolak-Salmon, P.; Berrut, G. Anticoagulant treatment in elderly patients with atrial fibrillation: A position paper. Geriatr. Psychol. Neuropsychiatr. Vieil. 2019, 17, 341–354. [Google Scholar] [CrossRef]
  6. Kirchhof, P.; Benussi, S.; Kotecha, D.; Ahlsson, A.; Atar, D.; Casadei, B.; Castella, M.; Diener, H.-C.; Heidbuchel, H.; Hendriks, J.; et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace 2016, 18, 1609–1678. [Google Scholar] [CrossRef] [PubMed]
  7. Papazoglou, A.S.; Moysidis, D.V.; Kartas, A.; Bekiaridou, A.; Samaras, A.; Giannakoulas, G. Oral anticoagulation challenges and therapeutic dilemmas in the very elderly: To treat and how to treat octogenarians and nonagenarians? Pol. Arch. Intern. Med. 2023, 133, 16508. [Google Scholar] [CrossRef]
  8. Besford, M.; Graham, S.; Sammon, C.; Mehmud, F.; Allan, V.; Alikhan, R.; Ramagopalan, S. Factors associated with non-prescription of oral anticoagulant treatment in non-valvular atrial fibrillation patients with dementia: A CPRD-HES study. Age Ageing 2020, 49, 679–682. [Google Scholar] [CrossRef] [PubMed]
  9. Kapoor, A.; Foley, G.; Zhang, N.; Zhou, Y.; Crawford, S.; McManus, D.; Gurwitz, J. Geriatric Conditions Predict Discontinuation of Anticoagulation in Long-Term Care Residents With Atrial Fibrillation. J. Am. Geriatr. Soc. 2020, 68, 717–724. [Google Scholar] [CrossRef]
  10. Okumura, K.; Yamashita, T.; Akao, M.; Atarashi, H.; Ikeda, T.; Koretsune, Y.; Shimizu, W.; Suzuki, S.; Tsutsui, H.; Toyoda, K.; et al. Oral Anticoagulants in Very Elderly Nonvalvular Atrial Fibrillation Patients With High Bleeding Risks: ANAFIE Registry. JACC Asia 2022, 2, 720–733. [Google Scholar] [CrossRef] [PubMed]
  11. Kim, I.-S.; Kim, H.-J.; Kim, T.-H.; Uhm, J.-S.; Joung, B.; Lee, M.-H.; Pak, H.-N. Non-vitamin K antagonist oral anticoagulants have better efficacy and equivalent safety compared to warfarin in elderly patients with atrial fibrillation: A systematic review and meta-analysis. J. Cardiol. 2018, 72, 105–112. [Google Scholar] [CrossRef] [PubMed]
  12. Kim, H.M.; Choi, E.K.; Park, C.S.; Cha, M.-J.; Lee, S.-Y.; Kwon, J.-M.; Oh, S. Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in octogenarian patients with non-valvular atrial fibrillation. PLoS ONE 2019, 14, e0211766. [Google Scholar] [CrossRef]
  13. Lai, C.L.; Chen, H.M.; Liao, M.T.; Lin, T.T. Dabigatran, Rivaroxaban, and Warfarin in the Oldest Adults with Atrial Fibrillation in Taiwan. J. Am. Geriatr. Soc. 2018, 66, 1567–1574. [Google Scholar] [CrossRef]
  14. Lee, S.; Monz, B.U.; Clemens, A.; Brueckmann, M.; Lip, G.Y.H. Representativeness of the dabigatran, apixaban and rivaroxaban clinical trial populations to real-world atrial fibrillation patients in the United Kingdom: A cross-sectional analysis using the General Practice Research Database. BMJ Open 2012, 2, e001768. [Google Scholar] [CrossRef] [PubMed]
  15. Oqab, Z.; Pournazari, P.; Sheldon, R.S. What is the Impact of Frailty on Prescription of Anticoagulation in Elderly Patients with Atrial Fibrillation? A Systematic Review and Meta-Analysis. J. Atr. Fibrillation 2018, 10, 1870. [Google Scholar] [CrossRef]
  16. Samaras, A.; Kartas, A.; Vasdeki, D.; Dividis, G.; Forozidou, E.; Fotos, G.; Kotsi, E.; Paschou, E.; Tsoukra, P.; Goulas, I.; et al. Rationale and design of a randomized study comparing Motivational Interviewing to Support Oral Anticoagulation adherence versus usual care in patients with nonvalvular atrial fibrillation: The MISOAC-AF trial. Hell. J. Cardiol. 2020, 61, 453–454. [Google Scholar] [CrossRef] [PubMed]
  17. Tzikas, A.; Samaras, A.; Kartas, A.; Vasdeki, D.; Fotos, G.; Dividis, G.; Paschou, E.; Forozidou, E.; Tsoukra, P.; Kotsi, E.; et al. Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with non-valvular Atrial Fibrillation (MISOAC-AF): A randomized clinical trial. Eur. Heart J. Cardiovasc. Pharmacother. 2021, 7, f63–f71. [Google Scholar] [CrossRef] [PubMed]
  18. Patsiou, V.; Samaras, A.; Kartas, A.; Moysidis, D.V.; Papazoglou, A.S.; Bekiaridou, A.; Baroutidou, A.; Ziakas, A.; Tzikas, A.; Giannakoulas, G. Prognostic implications of adherence to oral anticoagulants among patients with atrial fibrillation: Insights from MISOAC-AF trial. J. Cardiol. 2023, 81, 390–396. [Google Scholar] [CrossRef] [PubMed]
  19. Caldeira, D.; Nunes-Ferreira, A.; Rodrigues, R.; Vicente, E.; Pinto, F.J.; Ferreira, J.J. Non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis. Arch. Gerontol. Geriatr. 2019, 81, 209–214. [Google Scholar] [CrossRef] [PubMed]
  20. Patti, G.; Lucerna, M.; Pecen, L.; Siller-Matula, J.M.; Cavallari, I.; Kirchhof, P.; De Caterina, R. Thromboembolic Risk, Bleeding Outcomes and Effect of Different Antithrombotic Strategies in Very Elderly Patients With Atrial Fibrillation: A Sub-Analysis From the PREFER in AF (PREvention oF Thromboembolic Events–European Registry in Atrial Fibrillation). J. Am. Heart Assoc. 2017, 6, e005657. [Google Scholar] [CrossRef] [PubMed]
  21. Eikelboom, J.W.; Wallentin, L.; Connolly, S.J.; Ezekowitz, M.; Healey, J.S.; Oldgren, J.; Yang, S.; Alings, M.; Kaatz, S.; Hohnloser, S.H.; et al. Risk of Bleeding With 2 Doses of Dabigatran Compared With Warfarin in Older and Younger Patients With Atrial Fibrillation. Circulation 2011, 123, 2363–2372. [Google Scholar] [CrossRef] [PubMed]
  22. Halperin, J.L.; Hankey, G.J.; Wojdyla, D.M.; Piccini, J.P.; Lokhnygina, Y.; Patel, M.R.; Breithardt, G.; Singer, D.E.; Becker, R.C.; Hacke, W.; et al. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the rivaroxaban once daily, oral, direct factor xa inhibition compared with vitamin k antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation 2014, 130, 138–146. [Google Scholar] [CrossRef]
  23. Halvorsen, S.; Atar, D.; Yang, H.; De Caterina, R.; Erol, C.; Garcia, D.; Granger, C.B.; Hanna, M.; Held, C.; Husted, S.; et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: Observations from the ARISTOTLE trial. Eur. Heart J. 2014, 35, 1864–1872. [Google Scholar] [CrossRef] [PubMed]
  24. Giugliano, R.P.; Ruff, C.T.; Braunwald, E.; Murphy, S.A.; Wiviott, S.D.; Halperin, J.L.; Waldo, A.L.; Ezekowitz, M.D.; Weitz, J.I.; Špinar, J.; et al. Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N. Engl. J. Med. 2013, 369, 2093–2104. [Google Scholar] [CrossRef]
  25. Joglar, J.A.; Chung, M.K.; Armbruster, A.L.; Benjamin, E.J.; Chyou, J.Y.; Cronin, E.M.; Deswal, A.; Eckhardt, L.L.; Goldberger, Z.D.; Gopinathannair, R.; et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2024, 149, E1–E156. [Google Scholar] [CrossRef] [PubMed]
  26. Poli, D.; Antonucci, E.; Ageno, W.; Bertù, L.; Migliaccio, L.; Martinese, L.; Pilato, G.; Testa, S.; Palareti, G. Oral anticoagulation in very elderly patients with atrial fibrillation: Results from the prospective multicenter START2-REGISTER study. PLoS ONE 2019, 14, e0216831. [Google Scholar] [CrossRef] [PubMed]
  27. Rutherford, O.C.W.; Jonasson, C.; Ghanima, W.; Söderdahl, F.; Halvorsen, S. Effectiveness and safety of oral anticoagulants in elderly patients with atrial fibrillation. Heart 2022, 108, 345–352. [Google Scholar] [CrossRef]
  28. Connolly, S.J.; Ezekowitz, M.D.; Yusuf, S.; Eikelboom, J.; Oldgren, J.; Parekh, A.; Pogue, J.; Reilly, P.A.; Themeles, E.; Varrone, J.; et al. Dabigatran versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 2009, 361, 1139–1151. [Google Scholar] [CrossRef] [PubMed]
  29. Granger, C.B.; Alexander, J.H.; McMurray, J.J.V.; Lopes, R.D.; Hylek, E.M.; Hanna, M.; Al-Khalidi, H.R.; Ansell, J.; Atar, D.; Ave-zum, A.; et al. Apixaban versus Warfarin in Patients with Atrial Fibrillation. N. Engl. J. Med. 2011, 365, 981–992. [Google Scholar] [CrossRef] [PubMed]
  30. Joosten, L.P.T.; Van Doorn, S.; Van De Ven, P.M.; Köhlen, B.T.; Nierman, M.C.; Koek, H.L.; Hemels, M.E.; Huisman, M.V.; Kruip, M.; Faber, L.M.; et al. Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial. Circulation 2024, 149, 279–289. [Google Scholar] [CrossRef]
  31. Ding, J.; Sun, Y.; Zhang, K.; Huang, W.; Tang, M.; Zhang, D.; Xing, Y. Effects of Anticoagulant Therapy and Frailty in the Elderly Patients with Atrial Fibrillation. Clin. Interv. Aging 2024, 19, 247–254. [Google Scholar] [CrossRef] [PubMed]
  32. Camm, A.J.; Cools, F.; Virdone, S.; Bassand, J.-P.; Fitzmaurice, D.A.; Fox, K.A.A.; Goldhaber, S.Z.; Goto, S.; Haas, S.; Mantovani, L.G.; et al. Mortality in Patients With Atrial Fibrillation Receiving Nonrecommended Doses of Direct Oral Anticoagulants. J. Am. Coll. Cardiol. 2020, 76, 1425–1436. [Google Scholar] [CrossRef] [PubMed]
  33. Kartas, A.; Samaras, A.; Vasdeki, D.; Dividis, G.; Fotos, G.; Paschou, E.; Forozidou, E.; Tsoukra, P.; Kotsi, E.; Goulas, I.; et al. Flaws in Anticoagulation Strategies in Patients With Atrial Fibrillation at Hospital Discharge. J. Cardiovasc. Pharmacol. Ther. 2019, 24, 225–232. [Google Scholar] [CrossRef] [PubMed]
  34. Tzeis, S.; Savvari, P.; Skiadas, I.; Patsilinakos, S.; Stamatelopoulos, K.; Kourouklis, S.; Kyrikos, S.; Tsatiris, K.; Menegas, D.; Hahalis, G.; et al. Right drug, wrong dosage: Insights from the PAVE-AF antithrombotic study in older patients with atrial fibrillation. J. Thromb. Thrombolysis 2021, 51, 81. [Google Scholar] [CrossRef]
  35. Pilotto, A.; Veronese, N.; Polidori, M.C.; Strandberg, T.; Topinkova, E.; Cruz-Jentoft, A.J.; Custodero, C.; Maggi, S.; on behalf of the EUROSAF Study Investigators. The role of prognostic stratification on prescription of anticoagulants in older patients with atrial fibrillation: A multicenter, observational, prospective European study (EUROSAF). Ann. Med. 2022, 54, 2411. [Google Scholar] [CrossRef] [PubMed]
Figure 1. Kaplan–Meier curves plotted to illustrate the association of VKAs or DOACs with the occurrence of any: (A) all-cause mortality, (B) stroke, (C) major bleeding episode, (D) AF- or HF-related hospitalization or cardiovascular death.
Figure 1. Kaplan–Meier curves plotted to illustrate the association of VKAs or DOACs with the occurrence of any: (A) all-cause mortality, (B) stroke, (C) major bleeding episode, (D) AF- or HF-related hospitalization or cardiovascular death.
Jcdd 12 00086 g001
Figure 2. Kaplan–Meier curves plotted to illustrate the association of full or reduced DOAC dose with the occurrence of any: (A) all-cause mortality, (B) stroke, (C) major bleeding episode, (D) AF- or HF-related hospitalization or cardiovascular death.
Figure 2. Kaplan–Meier curves plotted to illustrate the association of full or reduced DOAC dose with the occurrence of any: (A) all-cause mortality, (B) stroke, (C) major bleeding episode, (D) AF- or HF-related hospitalization or cardiovascular death.
Jcdd 12 00086 g002
Table 1. Baseline characteristics according to oral anticoagulation scheme prescribed.
Table 1. Baseline characteristics according to oral anticoagulation scheme prescribed.
All Patients Under OACs
(n = 450, 100%)
Patients Under VKA
(n = 164, 36.4%)
Patients Under DOAC
(n = 286, 63.6%)
p-Value
Demographics
Male gender, n (%) 213 (47.3)77 (47)136 (47.6)0.90
Age, mean (SD)81.9 (4.3)81 (4.2)81.2 (4.3)0.85
Type of AF
Temporal type of AF, n (%)445163282
First diagnosed AF, n (%)40 (9)10 (2.2)30 (6.7)0.29
Paroxysmal AF or atrial flutter, n (%)137 (30.8)42 (9.4)95 (21.3)0.29
Persistent or permanent AF, n (%)268 (60.2)111 (24.9)157 (35.3)0.29
Cardiovascular risk factors and comorbidities
BMI (kg/m2), mean (SD)28 (4.8)27.6 (4.9)28 (4.8)0.84
History of smoking (prior or current), n (%)234 (53.3)84 (52.2)150
(54)
0.72
Serum creatinine (mg/dL), mean (SD)1.33 (0.88)1.37 (0.86)1.16 (0.41)<0.01
CHA2DS2-VASc score, mean (SD)5.4 (1.4)5.8 (1.6)5.3 (1.4)<0.01
HAS-BLED score, mean (SD)12 (0.9)2.43 (1.0)1.7 (0.8)<0.01
HAS-BLED ≥ 3, n (%)118 (26.2)77 (47)41 (14.3)<0.01
Estimated GFR with Cockcroft–Gault formula, mean (SD)27.5 (29.69)24 (27)28.6 (30.8) 0.02
Estimated GFR with CKD-EPI formula, mean (SD)53.4 (19.9)51.9 (19.5)56.3 (18.3) 0.43
Hemoglobin (g/dL), mean (SD)12.30 (2.32)12.3 (2.3)12.4 (2.5) 0.29
Coronary artery disease, n (%)270 (60.9)117 (71.8)153
(54.6)
<0.01
Heart failure, n (%)270 (60.9)117 (71.8)153
(54.6)
<0.01
Prior myocardial infarction, n (%)270 (60.9)117 (71.8)153
(54.6)
<0.01
Pacemaker/ ICD, n (%)48 (2.5)25 (5.7)23 (5.2)0.07
Hypertension, n (%)389 (87.4)131 (80.9)258 (91.2)<0.01
Dyslipidemia, n (%)218 (49.2)86 (52.8)132 (47.1)0.25
Diabetes mellitus, n (%)165 (37.1)68
(41.7)
97
(34.4)
0.12
Peripheral artery disease, n (%)217 (49.3)95 (59)122 (43.7)<0.01
Prior ischemic stroke (%) 57 (12.8)25 (15.5)32 (11.2)0.19
Prior systemic thromboembolic disease, n (%)38 (8.5)19 (11.8)19 (6.6)0.06
Prior intracranial bleeding, n (%)3 (0.7)2 (1.2)1 (0.4)0.27
Prior upper gastrointestinal bleeding, n (%)35 (7.9)14 (8.7)21 (7.4)0.62
Prior lower gastrointestinal bleeding, n (%)36 (8.1)13 (2.9)23 (8.1)0.99
Prior bleeding episodes, n (%)147 (33)57 (35.4)90 (31.7)0.42
Chronic kidney disease, n (%)269 (60.6)107
(66)
162 (57.4)0.07
Hepatic disease, n (%)9 (2.1)3 (1.9)6 (2.2)0.83
Thyroid disease, n (%)96 (21.8)32 (19.9)64 (22.9)0.45
Medication
Use of rate control medication at discharge (b-blocker, digoxin, or both), n (%)362 (80.4)128 (78)234 (81.8)0.33
Use of antiplatelets at discharge (aspirin, clopidogrel, or both), n (%)75 (17.1)49 (29.9)26
(9.5)
<0.01
Use of rhythm control medication at discharge (propafenone, amiodarone, sotalol), n (%)79 (17.6)27 (16.5)52 (18.2)0.65
Table 2. Baseline patient characteristics according to DOAC dose (full vs. reduced).
Table 2. Baseline patient characteristics according to DOAC dose (full vs. reduced).
All Patients Under DOACs (N = 286, 100%)Reduced Dose of DOACs (N = 190, 66.4%)Full Dose of DOACs (N = 96, 33.6%)p-Value
Demographics
Male gender, n (%)134 (46.9)97 (51.1)37 (38.5)0.04
Age (years), mean (SD)81.2 (4.3)81.9 (4.4)79.9 (3.7)<0.01
Type of AF
First diagnosed AF, n (%)30 (10.8)15 (16)15 (8.1)0.12
Paroxysmal AF or atrial flutter, n (%)94 (33.7)66 (35.7)28 (29.8)0.12
Persistent or permanent AF, n (%)155 (55.6)104 (56.2)51 (54.3)0.12
Cardiovascular risk factors and comorbidities
BMI (kg/m2), mean (SD)28.0 (4.8)27.6 (4.7)28.9 (4.8)0.03
History of smoking (prior or current), n (%)148 (53.8)106 (58.2)42 (45.2)0.04
Serum creatinine (mg/dL), mean (SD)1.16 (0.4)1.2 (0.4)1 (0.3)<0.01
CHA2DS2-VASc score, mean (SD)5.3 (1.4)5.3 (1.3)5.2 (1.4)0.47
HAS-BLED score, mean (SD)1.7 (0.8)1.7 (0.8)1.7 (0.8)0.94
HAS-BLED ≥ 3, n (%)41 (14.5)29 (15.4)12 (12.6)0.53
Estimated GFR with Cockcroft–Gault formula, mean (SD)28.6 (30.8)29.2 (29.2)27.1 (34.0)0.59
Estimated GFR with CKD-EPI formula, mean (SD)56.3 (18.3)52 (17.7)64.5 (16.5)<0.01
Hemoglobin (g/dL), mean (SD)12.4 (2.5)12.4 (2.7)12.4 (2.0)0.91
Coronary artery disease, n (%)91 (32.4)72 (38.7)19 (20.0)<0.01
Heart failure, n (%)164 (58)116 (61.7)48 (50.5)0.07
Prior myocardial infarction, n (%)48 (17.3)41 (22.3)7 (7.5)<0.01
Pacemaker/ ICD, n (%)23 (8.3)17 (9.2)6 (6.5)0.28
Hypertension, n (%)256 (91.4)169 (90.9)87 (92.6)0.63
Dyslipidemia, n (%)130 (46.9)84 (45.7)46 (49.5)0.55
Diabetes mellitus, n (%)97 (34.8)62 (33.3)35 (37.6)0.48
Peripheral artery disease, n (%)120 (43.5)87 (47.5)33 (35.5)0.06
Prior ischemic or hemorrhagic stroke or transient ischemic attack, n (%)47 (16.7)34 (18.1)13 (13.8)0.63
Systemic thromboembolic disease, n (%)19 (6.7)14 (7.4)5 (5.3)0.49
Prior intracranial bleeding, n (%)1 (0.4)1 (0.5)0 (0.0)0.47
Prior upper gastrointestinal bleeding, n (%)21 (7.5)13 (7.0)8 (8.4)0.67
Prior lower gastrointestinal bleeding, n (%)23 (8.2)15 (8.1)8 (8.4)0.92
Prior bleeding episodes, n (%)90 (32.0)56 (30.1)34 (35.8)0.33
Chronic kidney disease, n (%)161 (57.7)126 (68.1)35 (37.2)<0.01
Hepatic disease6 (2.2)4 (2.2)2 (2.2)0.98
Medication
Use of rate control medication at discharge (b-blocker, digoxin, or both), n (%)231 (81.6)152 (80.9)79 (83.2)0.90
Use of antiplatelets at discharge (aspirin, clopidogrel, or both), n (%)25 (9.1)21 (11.4)4 (4.4)0.10
Use of rhythm control medication at discharge (propafenone, amiodarone, sotalol), n (%)52 (18.3)33 (20)19 (6.7)0.35
Table 3. Logistic regression outcomes for the prediction of VKA prescription at hospital discharge.
Table 3. Logistic regression outcomes for the prediction of VKA prescription at hospital discharge.
Univariate p-ValueMultivariate p-ValueAdjusted OR
(95% CIs)
Female gender0.900.941.02 (0.55–1.90)
Age0.630.710.99 (0.94–1.05)
Smoking (ever)0.720.810.94 (0.57–1.55)
Body mass index0.690.620.99 (0.94–1.04)
CHA2DS2-VASc score<0.010.020.69 (0.50–0.95)
HAS-BLED score<0.01<0.010.33 (0.23–0.48)
Coronary artery disease<0.010.800.93 (0.52–1.66)
Hypertension<0.01<0.014.80 (2.30–10.00)
Diabetes mellitus0.120.241.43 (0.79–2.58)
Chronic kidney disease0.080.090.64 (0.39–1.07)
Prior stroke or TIA0.05<0.014.90 (1.8–13.44)
Prior major bleeding0.940.012.72 (1.26–5.88)
Antiplatelet use<0.010.050.74 (0.54–1.00)
Table 4. Survival analysis outcomes based on the type of OAC received (VKA vs. DOACs).
Table 4. Survival analysis outcomes based on the type of OAC received (VKA vs. DOACs).
Outcome Rates of Occurrence in VKARates of Occurrence in DOACsLog-Rank Test p-ValueUnivariate HR
Cis (95%)
Multivariate HR * Cis (95%)
All-cause mortality90 (54.9)113 (39.5)0.0040.69 (0.50–0.88)0.79 (0.58–1.06)
CV mortality69 (42.1)80 (28.0)0.0030.62 (0.45–0.85)0.76 (0.53–1.07)
Bleeding5 (3.4)16 (6.1)0.3021.69 (0.62–4.60)1.50 (0.52–4.27
Stroke11 (7.5)11 (4.2)0.1100.51 (0.22–1.17)0.43 (0.17–1.08)
AF- or HF-related hospitalization or CV death116 (70.7)163 (57.0)0.2970.95 (0.64–1.43)0.84 (0.63–1.11)
* Cox regression analysis adjusted for age, gender, smoking, BMI, Hx of diabetes mellitus, Hx of HF, Hx of CAD, Hx of hypertension, Hx of CKD, Hx of stroke, and CHADS-VASc score.
Table 5. Logistic regression outcomes for the prediction of full vs. reduced DOAC dose prescription.
Table 5. Logistic regression outcomes for the prediction of full vs. reduced DOAC dose prescription.
CovariateUnivariate p-ValueMultivariate p-ValueAdjusted OR
(95% CIs)
Diabetes mellitus0.4770.4490.74 (0.35–1.60)
Age<0.0010.0331.09 (1.01–1.17)
Female gender0.0440.4500.73 (0.32–1.65)
Body mass index0.0350.9691.00 (0.94–1.07)
Smoking (ever)0.0400.0981.68 (0.91–3.12)
Heart failure0.0730.6391.20 (0.56–2.56)
Coronary artery disease0.0020.7301.18 (0.46–3.05)
Prior acute myocardial infarction0.0030.0693.01 (0.92–9.88)
Chronic kidney disease<0.001<0.0013.53 (1.92–6.49)
History of any stroke or TIA0.3660.9241.07 (0.26–4.45)
History of bleeding0.3350.1800.64 (0.33–1.23)
HAS_BLED > 30.5280.8541.09 (0.42–2.82)
CHA2DS2_VASC0.3340.8871.04 (0.64–1.67)
Table 6. Survival analysis outcomes based on the differentiation of full vs. reduced DOAC dose.
Table 6. Survival analysis outcomes based on the differentiation of full vs. reduced DOAC dose.
OutcomeRates of Occurrence in DOAC Reduced DoseRates of Occurrence in DOAC Full DoseLog-Rank Test p-ValueUnivariate HR (95% CIs)Multivariate aHR * (95% CIs)
All-cause mortality81 (43.1)32 (33.7)0.1181.32 (0.88–1.99)0.96 (0.60–1.53)
CV mortality59 (31.4)21 (22.1)0.1371.46 (0.89–2.40)0.84 (0.47–1.50)
Bleeding11 (6.6)5 (5.5)0.6591.24 (0.43–3.56)1.32 (0.42–4.16)
Stroke7 (4.2)4 (4.4)0.9930.97 (0.28–3.31)1.24 (0.27–5.70)
AF- or HF-related hospitalization or CV death93 (49.5)39 (41.1)0.8031.09 (0.75–1.59)0.79 (0.50–1.22)
* Cox regression analysis adjusted for age, gender, smoking, BMI, Hx of diabetes mellitus, Hx of HF, Hx of CAD, Hx of hypertension, Hx of CKD, Hx of stroke, and CHADS-VASc score.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Zergioti, M.; Kyriakou, M.; Papazoglou, A.S.; Kartas, A.; Moysidis, D.V.; Samaras, A.; Karagiannidis, E.; Kamperidis, V.; Ziakas, A.; Giannakoulas, G. Oral Anticoagulation Choice and Dosage in Very Elderly Patients with Atrial Fibrillation. J. Cardiovasc. Dev. Dis. 2025, 12, 86. https://doi.org/10.3390/jcdd12030086

AMA Style

Zergioti M, Kyriakou M, Papazoglou AS, Kartas A, Moysidis DV, Samaras A, Karagiannidis E, Kamperidis V, Ziakas A, Giannakoulas G. Oral Anticoagulation Choice and Dosage in Very Elderly Patients with Atrial Fibrillation. Journal of Cardiovascular Development and Disease. 2025; 12(3):86. https://doi.org/10.3390/jcdd12030086

Chicago/Turabian Style

Zergioti, Martha, Melina Kyriakou, Andreas S. Papazoglou, Anastasios Kartas, Dimitrios V. Moysidis, Athanasios Samaras, Efstratios Karagiannidis, Vasileios Kamperidis, Antonios Ziakas, and George Giannakoulas. 2025. "Oral Anticoagulation Choice and Dosage in Very Elderly Patients with Atrial Fibrillation" Journal of Cardiovascular Development and Disease 12, no. 3: 86. https://doi.org/10.3390/jcdd12030086

APA Style

Zergioti, M., Kyriakou, M., Papazoglou, A. S., Kartas, A., Moysidis, D. V., Samaras, A., Karagiannidis, E., Kamperidis, V., Ziakas, A., & Giannakoulas, G. (2025). Oral Anticoagulation Choice and Dosage in Very Elderly Patients with Atrial Fibrillation. Journal of Cardiovascular Development and Disease, 12(3), 86. https://doi.org/10.3390/jcdd12030086

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop