Atrial fibrillation is the most common form of arrhythmia and, in general, a disease that is becoming increasingly relevant from a clinical viewpoint.1,2 The estimated prevalence of atrial fibrillation is 1.0–2.0% in the population at large,1 with a tendency to increase with age, and reaching a prevalence of 8–10% in patients aged over 80 years.3–5 Prognosis of patients with atrial fibrillation is affected with a risk of death at least double if compared with patients with a normal sinus rhythm.6,7 Atrial fibrillation is associated with a two-fold to seven-fold increased risk of stroke; in addition, atrial fibrillation is believed to be present in at least 15% of all cases of stroke, and in 30% of cases in elderly patients.7–10
The management of patients with atrial fibrillation is particularly complex and depends on many factors, such as the type of arrhythmia and the patient's general characteristics. The aims of atrial fibrillation treatment are control of the heart rate, restoration and maintenance of the normal sinus rhythm and prevention of complications, particularly thromboembolism. Treatment of patients with atrial fibrillation includes both non-pharmacological and pharmacological methods. Pharmacological treatment of atrial fibrillation is based on many drugs, but the use of some of them, mostly antiarrhythmics, is limited by modest efficacy, frequent intolerance and the potential for ventricular proarrhythmia and organ toxicity.11 Of particular importance is the appropriate use of antithrombotic drugs,12–14 as well as their potential interference with concomitant treatments, and the need for strict monitoring for some of them (namely oral anticoagulants).
Patients with atrial fibrillation hospitalized in Internal Medicine departments represent a critical issue because of the high prevalence of arrhythmia and clinical peculiarities. In fact, patients hospitalized in Internal Medicine units often present multiple diseases and receive complex treatments, and this may considerably affect atrial fibrillation management. Moreover, available information on atrial fibrillation in clinical practice focuses on specific patient subsets, such as those cared for by cardiologists15,16 or general practitioners,17–20 and recent data on patients hospitalized in Internal Medicine wards are very limited. The aim of this study was to collect, in a real-world context, some data useful to better define the characteristics of this group of patients, and the therapeutic procedures adopted. This exploratory study should help us to shed light on the clinical characteristics of such patients and to focus on possible discrepancies between guideline recommendations and real-world management, owing to the complexity of patients and limits of existing treatment strategies.
FALP (Fibrillazione Atriale in Liguria e Piemonte) is a retrospective observational study performed under the scientific coordination of the Research Department of FADOI (Italian Federation of Internal Medicine) Foundation.
Data were collected at the beginning of 2010 in 18 Internal Medicine units of the regions Liguria and Piemonte (Italy). Each centre reviewed the hospital charts of the last 50 consecutive patients discharged during the year 2009 in whom a diagnosis of atrial fibrillation had been made (patient's history or during the index hospitalization). To estimate the prevalence of atrial fibrillation, each centre indicated the total number of patients discharged from the unit in the same time-window.
For each patient, the following information was registered: demography, clinical history for atrial fibrillation (classification, previous treatments), concomitant diseases and therapies at admission, management of atrial fibrillation during hospitalization (diagnosis/monitoring, therapies and possible side-effects) and treatments and diagnoses at discharge as assessed by administrative databases [hospital discharge records, the so-called scheda dimissione ospedaliera (SDO)].
The study was approved by the Ethics Committee of the coordinating centre, and it was notified to the Ethics Committees of all participating centres, according to Italian law.
Owing to the exploratory and descriptive aims of the study, no formal definition of the sample size was made.
Summary statistics were calculated for all patient variables. For non-continuous variables, frequency distribution was used.
The association between the prescription of oral anticoagulants at discharge and a number of possible predictors was evaluated by means of a multivariable logistic analysis. Covariates for this analysis were selected on the basis of clinical plausibility, and the list of variables includes age (>75 vs. ≤75 years), sex, classification of atrial fibrillation (paroxysmal vs. other), the possible presence of cerebrovascular disease, hypertension, diabetes, heart failure, cancer, hepatopathy, ischaemic heart disease/peripheral arterial disease, bleeding (active or in patient's history) and the number of concomitant drugs (>4 vs. ≤4). Odds ratios and 95% confidence intervals were reported with two-tailed probability values. A P value of 0.05 or less was considered statistically significant.
Statistical analyses were carried out using SAS software (version 9.1, SAS Institute Inc., Cary, North Carolina, USA).
A total of 903 patients were included in the study, and details of their characteristics are specified in Table 1. As detailed in Fig. 1, the majority of patients had multiple active comorbidities (63.4% of the patients had three or more chronic or active diseases other than atrial fibrillation) and received multiple pharmacological treatments (three or more drugs, excluding those for atrial fibrillation, in 64% of the patients). Around one of five patients (19.3%) had a positive anamnesis for ischaemic stroke (and one-third of these patients was receiving oral anticoagulant), and/or active stroke at the time of hospital admission.
Patients management during hospital stay
Mean duration of hospitalization in an Internal Medicine unit was 11.7 days (range 1–108). The prevalence of atrial fibrillation in the study setting was 18.2%. General characteristics of atrial fibrillation at admission to hospital and specific treatments in patients’ history are listed in Table 2. Of note, in 24% of the patients, atrial fibrillation was first detected during hospitalization. Twelve patients (1.3%) could be classified as having ‘lone’ atrial fibrillation.2
A measure of heart rate at hospital admission and at discharge was available for 740 patients. The percentage of patients with heart rate at rest within the target 60–80 beats/min1 was more than double at discharge (66.3%) vs. hospital admission (30.9%, P < 0.0001). All patients had at least one ECG during hospitalization, and in 40.3% of patients three or more ECGs were recorded. Among the 633 patients with at least two ECGs, 520 had atrial fibrillation at the first exam, and of these 67 had a sinus rhythm at the last control. Holter monitoring was performed in 3.0% of the patients, and echocardiogram in 29.8%. Additional testing related to atrial fibrillation was required in 114 patients (12.6%), and a consultancy by the cardiologist for 96 patients (10.6%).
During hospital stay, 80.5% of the patients received at least one treatment for atrial fibrillation, and the details are provided in Fig. 2. On the whole, 501 patients (55.5%) received an antithrombotic agent for atrial fibrillation, and 558 patients (61.8%) a drug for the arrhythmia which, in the majority of cases (47.2%), was aimed at obtaining rate control (11.2% for rhythm control and 3.4% for both rate with rhythm control). When done, direct current and pharmacological cardioversion were considered effective in four of seven (57.1%) and 38 of 44 (86.4%) patients, respectively.
In the subgroup of patients with diagnosis of atrial fibrillation known before hospitalization, it was shown that during hospital stay rate or rhythm control treatment was introduced in 108 (12.0%) patients, withheld in 58 (6.4%) and maintained in 283 (31.3%). As for antithrombotic prophylaxis, it was introduced in 142 (15.7%), withheld in 113 (12.5%) and maintained in 254 (28.1%) patients.
By combining patients’ history and events that occurred during hospitalization, 116 patients (12.8%) experienced side-effects related to treatment for atrial fibrillation, the more frequent being bleeding (68 patients), bradycardia/other arrhythmias (28 patients) and thyroid dysfunction (six patients).
In-hospital mortality was 13.4%, and 4.6% of the patients were transferred from Internal Medicine to other units. Among the 782 patients discharged from the hospital or transferred to other units, 696 (89%) received prescription of at least one pharmacological treatment for atrial fibrillation (70.2% received a drug for rate or rhythm control and 68.9% an antithrombotic treatment, respectively, Table 3). In addition, 88 patients (11.2%) received prescription for antithrombotic treatment for indication other than atrial fibrillation.
Figure 3 reports the thromboembolic risk profile of patients [according to cardiac failure, hypertension age, diabetes, stroke (CHADS)2 score and indications by the American College of Chest Physicians (ACCP)],12–14 and the percentage of patients receiving antithrombotic treatment for atrial fibrillation at home, in each category. In patients with CHADS2 score of at least 2 or ACCP risk profile ‘intermediate–high’/‘high’, for whom treatment with oral anticoagulant is indicated, antiplatelet agents for atrial fibrillation were prescribed in 28.7 and 28.8% of the patients, respectively. In the case of patients with indications to aspirin or no antithrombotic treatment (CHADS2 score = 0 or ACCP risk profile ‘low’), oral or parenteral anticoagulant was used in 50% of the patients.
Potential predictors for the prescription of oral anticoagulants have been evaluated by means of a multivariable analysis, the results of which are reported in Table 4. Patients with hypertension had a greater chance of being treated with vitamin K antagonists (P < 0.05), although previous bleeding (P < 0.001), age above 75 years (P < 0.001), paroxysmal atrial fibrillation (P < 0.001), male sex (P < 0.01) and a number of concomitant medications of more than four (P < 0.05) were strong negative predictors of prescription of oral anticoagulants.
By reviewing hospital records (SDO), atrial fibrillation was reported at discharge in 682 patients (75.5%). In the details, atrial fibrillation was reported as the primary diagnosis in 31 cases (3.4%), and as the first, second and third or more than third coexisting condition in 22.5, 22.7 and 26.9% of patients, respectively. The more frequent primary diagnoses recorded in SDO were heart failure (28.4%), pneumonia (7.6%), ischaemic stroke (6.3%), respiratory insufficiency (6.0%), cancer (5.5%), acute infection (3.7%) and chronic obstructive pulmonary disease (3.4%).
This observational study provides an updated real-world snapshot of the characteristics and management of patients with atrial fibrillation hospitalized in Internal Medicine wards. Internal Medicine units very often admit patients with advanced age, multiple comorbidities and a number of treatments, and this may considerably influence atrial fibrillation management. In this perspective, our data may be of interest and add interesting information to this topic.
Atrial fibrillation is recognized as an increasingly growing problem of healthcare, owing to a combination of factors including aging, and the rising prevalence of underlying conditions such as ischaemic heart disease or heart failure.1,2,21 Internal Medicine is a setting where this trend may be amplified, owing to the more advanced age and the high number of comorbidities of the patients hospitalized in these units. Our study confirms that atrial fibrillation is a very frequent finding among patients hospitalized in Internal Medicine units, with a prevalence close to 20%. Furthermore, according to our data, around one of 20 patients admitted to Internal Medicine units for any reason receives a diagnosis of ‘de-novo’ atrial fibrillation during the hospital stay.
One of the major findings of our study is the high all-cause in-hospital mortality. In fact, the overall in-hospital death in this study is far higher than that observed in two recent surveys we performed in Internal Medicine units in Italy, the first considering all consecutive patients hospitalized for any cause22 and the second which enrolled patients with heart failure.23 In these two surveys mean age of the patients and burden of comorbidities were slightly lower than those registered in the present study, and this is a plausible explanation for the observed worse prognosis. Although the study design does not allow speculating on this issue, we cannot rule out a possible role of atrial fibrillation per se in determining prognosis, thus confirming that atrial fibrillation is not a benign disease.2 This issue is probably worth addressing in future specifically designed studies.
The present study confirms that patients hospitalized in Internal Medicine units have a high degree of comorbidity, and only very few had ‘lone atrial fibrillation’, with a far lower prevalence if compared with other clinical settings.15,24,25 This condition reasonably affects prognosis, and it influences patient management as well. Of particular interest is the concomitant presence of atrial fibrillation and heart failure which occurred in 29.4% of the patients in our study. It is known that the combination of atrial fibrillation and heart failure is associated with increased morbidity and mortality compared with each disorder alone. Atrial fibrillation and heart failure share common mechanisms and treatment strategies, and drugs such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have been proposed as upstream therapies for atrial fibrillation, both in patients with or without heart failure.1,26
Management of patients with atrial fibrillation involves three principal objectives: rate control, rhythm control and prevention of thromboembolism. Rhythm control was thought to have potential advantages over rate control, but this concept is at present only theoretical, given the findings from large randomized clinical trials which showed that rate control seems safer and as effective as rhythm control.27,28 This suggests that available rhythm control strategies are probably inadequate and that there is an unmet need for safe and efficacious antiarrhythmics for control of atrial fibrillation.15 In this perspective, new drugs such as dronedarone or atrial specific agents could enrich the therapeutic scenario in the near future.11,29 Although some aspects of rate control are still under debate (optimal target of heart rate, lenient vs. strict rate control),1,2,30,31 this strategy is, therefore, preferred by most physicians as therapy for patients with atrial fibrillation. Rhythm control may be considered as an initial approach for younger individuals, especially those with paroxysmal lone atrial fibrillation, and should be applied only in symptomatic patients.2 Coherently with these assumptions, and with the high percentage of permanent atrial fibrillation we observed, in our study the majority of patients received typical rate control drugs (digoxin/β-blockers, verapamil or diltiazem), and drugs for rhythm control were more frequently used in symptomatic than in asymptomatic patients (18 vs. 8.6%) and in those with paroxysmal vs. non-paroxysmal atrial fibrillation (27.6 vs. 11.7%).
Atrial fibrillation is a strong, independent risk factor for stroke.32,33 A number of algorithms are available to stratify the risk of stroke in patients with atrial fibrillation, the most popular being based on the CHADS2 score13,14 and the indications by the American College of Chest Physicians.12 We applied these classifications to the patients of our study, and they appeared to have an elevated risk, as more than three-quarters of the patients were in those categories (CHADS2 score 2–6 /ACCP risk intermediate–high or high) for which guidelines recommend treatment with oral anticoagulants. In our study, the number of patients in the lowest classes of risk was very limited. If related to a recently proposed scoring system, called Cardiac failure, hypertension, age at least 75 (doubled), diabetes, stroke (doubled), vascular disease, age 65–74 years, sex category (female)34 only six patients in our population (0.6%) belonged to the category which would not need any antithrombotic therapy.
The incidence of stroke in patients with atrial fibrillation can be substantially reduced by using antithrombotic prophylaxis33 and, therefore, an antithrombotic preventive treatment is recommended for the majority of atrial fibrillation patients, including those with paroxysmal atrial fibrillation.1,2,12 However, several observational studies have documented in different settings that compliance with the above recommendation is far from satisfactory, especially with respect to oral anticoagulants.15,20,32,35–37 In our study, the overall mean percentage of patients receiving an antithrombotic treatment for atrial fibrillation was around 55% during hospitalization and near 70% at discharge. This difference can be only partially accounted for by the high rate of patients without antithrombotic therapy who died. The figures of antithrombotic treatment assessed in our study are not easy to compare with data from the literature, due to heterogeneity among available studies as for design and target population. The percentage of antithrombotic treatment we observed at discharge was slightly higher than those previously reported in Italy in in-patients37 and outpatients,20 but lower than those shown in prospective registries in cardiologic settings.15,16 Furthermore, the retrospective design of the study did not allow exact identification of patients with actual contraindication to antithrombotic treatment, and we cannot draw any conclusion on the suboptimal use of antithrombotics. However, if we also consider the background use of antithrombotics for indications other than atrial fibrillation, three of four of our patients received chronic preventive antithrombotic treatment at discharge.
Although there is a consensus that oral anticoagulants offer better protection than antiplatelets against ischaemic stroke in patients with atrial fibrillation,1,2,38–40 these drugs are frequently underused in patients with atrial fibrillation, with reported percentages of prescription between 30 and 60% in most of the studies.15,20,37,41–43 The tendency toward underuse of oral anticoagulants seems confirmed in our study. In fact, at least 75% of the patients had indication for this treatment according to CHADS2 score or ACCP, but less than half actually received it. The gap between guidelines and clinical practice is not completely attributable to the presence of contraindications, although they are not negligible in atrial fibrillation patients.44–46 As known, vitamin K antagonists are cumbersome to use, and the caring doctors have a number of factors to consider in evaluating whether a patient should receive oral anticoagulants or not. In our study, patients with hypertension were more frequently treated with vitamin K antagonists, while previous bleeding, age above 75 years, paroxysmal atrial fibrillation, male sex and a number of concomitant drugs of more than four were strong negative predictors of prescription of oral anticoagulants. Hypertension is a major risk factor for stroke, and its presence led physicians to adopt preventive anticoagulation more frequently. Despite the risk of stroke being similar for paroxysmal vs. persistent/permanent atrial fibrillation,47,48 as previously reported,32 we showed that classification of atrial fibrillation guided the treatment decision toward the use of oral anticoagulant, although it should not be the case. Of interest is the negative association between the number of concurrent medications and treatment with oral anticoagulant, opposite to that shown by a recent survey in the setting of primary care.20 This finding may be due to the concern that polytherapy will increase the risk of bleeding, or that patients with a significant burden of diseases may have more disadvantages than benefits from anticoagulant treatment. The same may apply to the negative correlation between aging and prescription of vitamin K antagonists.
As a further explanation for the gap between indication and prescription of oral anticoagulants, some authors have suggested a lack of awareness among clinicians of patient risk stratification criteria, or poor appreciation of the risk–benefit ratio of vitamin K antagonists, with an overestimation of their bleeding risks.20,49 In our study, risk stratification criteria did not significantly drive the use of oral anticoagulants, as these drugs were prescribed at discharge in 31.5% of the patients with CHADS2 score 0–1 and in 34.1% of those with CHADS2 score 2–6. However, it has to be kept in mind that in clinical practice anticoagulation treatment is highly dependent on the individual patient and takes into account factors such as age, feasibility of adequate monitoring of therapy, comorbidities and the patient's lifestyle and personal preference. Thus, the decision not to give anticoagulants for a patient eligible for anticoagulation may still be the most appropriate strategy for that individual. Apart from this, it is likely that at present anticoagulation in patients with atrial fibrillation is globally suboptimal. Simplification of thromboprophylaxis in atrial fibrillation patients is long overdue for real-life clinical practice, and the availability of the new anticoagulants that would overcome the inherent restrictions and disadvantages of vitamin K antagonists may facilitate their use.50–51
Our study, due to its design, may have some intrinsic limitations. Retrospective audits may be affected by incomplete data recording in the source documents, and we cannot exclude that this has led to underestimation of some figures (e.g. those related to patients’ history, or adverse events due to treatment for atrial fibrillation). Furthermore, some assessments, such as patients’ eligibility for anticoagulant treatment, were difficult to make. On the contrary, the retrospective design of the study allows a rigorous description of the management of patients in clinical practice which was not influenced by the study itself. Our study had a descriptive aim, and it was neither powered to assess prevalence of atrial fibrillation in Internal Medicine units nor the association between anticoagulant treatment and predictors of use. For this latter, we were not able to include in our analysis potential predictors such as those related to social environment, or cognitive status of the patient. The information we provide has, therefore, to be taken as an indication, although reliable and interesting. Finally, our study was confined to two regions of Italy, and we cannot tout court extrapolate the results either to the whole country or to the overall setting of Internal Medicine units. However, as we included hospitals of different location (from cities to small towns) and healthcare organization, we consider our setting representative enough of Internal Medicine units in Italy. It is possible that the therapeutic approach of patients with atrial fibrillation may be different between Internal Medicine and Cardiology wards, owing to reasons such as different age and comorbidities of the patients. A response to this question will be provided by the ATA-AF study (collaborative research ongoing in Italy and involving scientific societies in the cardiology – ANMCO – and the internal medicine –FADOI – field).
In conclusion, atrial fibrillation is a frequent finding in patients hospitalized in Internal Medicine units, with a prevalence of nearly 20%. Patients with atrial fibrillation hospitalized in Internal Medicine units are of advanced age, with a high grade of comorbidity, and characterized by a severe prognosis. These features, added to the existence of some ‘grey zones’ even in the most recent international guidelines (especially in the elderly), make management of patients challenging. More precise indications on some open issues relevant to patients’ treatment and improved treatment strategies (convenient to use other than effective and safe) are needed to optimize atrial fibrillation management in the heterogeneous real-world clinical practice.
The study was supported by an unrestricted grant from Sanofi Aventis Italia, having no involvement in the study design, management, analysis and reporting.
There are no conflicts of interest.
The authors are indebted to Irene Zaratti and Davide Ghilardi for data management and organization.
Members of the FALP Study Group:
F. Orlandini (La Spezia); R. Cavaliere, C. Norbiato (Torino); I. Brandolin, F. Raggi (Genova); M.C. Bertoncelli (Vercelli); A. Rossi (Novara); P. Davio, G. Aiosa, C. Donati (Alessandria); E. Haupt, D. Bessarione (Lavagna - GE); F. Torta, A. Martini (Chieri - TO); M. Delucchi, M.P. Checcucci, S. Reynaud (Saluzzo - CN); C. Marengo, M. Grigoletto (Moncalieri - TO); G. Imperiale (Torino); C. Pascale, A. Bosio, F. Cerrato, O. Pallisco (Torino); S. Pesce, M. Giannotti (Genova); M. Dugnani, G. Cornaglia (Galliate - NO); G. Bertinieri, S. Giovannetti (Biella); T. Defranceschi, R. Durante (Albenga - SV); M. Carosio, A. Marandino (Pinerolo - TO); G. Calò (Verbania).
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