JAMDA xxx (2015) 1e4

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Original Study

Treatment of Nonagenarians With Atrial Fibrillation: Insights From the Berlin Atrial Fibrillation (BAF) Registry Alexander Wutzler MD, MA *, Sophie von Ulmenstein, Philipp Attanasio MD, Martin Huemer MD, Abdul Shokor Parwani MD, Leif-Hendrik Boldt MD, Wilhelm Haverkamp MD Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin

a b s t r a c t Keywords: Atrial fibrillation elderly nonagenarians anticoagulation

Objectives: The objective of this study was to determine course and treatment of atrial fibrillation (AF) in nonagenarians. Incidence of AF increases with age. Due to the demographic change in the industrialized world, an increase of AF in the group of elderly and very elderly is expected in the next decades. However, only few data exist on the clinical relevance of AF in patients aged 89 years or older. Design: Observational, mono-centric registry. Setting: University hospital. Participants: Of the 11,888 patients included in the Berlin Atrial Fibrillation (BAF) Registry, 279 patients aged 89 years or older were identified. All patients presented to our hospital with AF between January 2001 and December 2014. Measurements: AF type, symptoms, comorbidities, CHA2DS2-VASc and HAS-BLED, treatment strategy, and anticoagulant treatment were assessed at baseline. A composite of stroke/transient ischemic attack (TIA), thromboembolic events, major bleeding, and death was the primary endpoint. Stroke/TIA, thromboembolic events and major bleeding, presence of AF, new onset of heart failure and change of NYHA class, and bradyarrhythmia necessitating pacemaker implantation were secondary endpoints. Results: Patients (age 92  2.7 years, range 89e108) presented in EHRA class I in 38.4% of the cases, class II in 49.5%, class III in 10%, and class IV in 2%. Rhythm control was attempted in 37 (13.3%) of the patients. Baseline CHA2DS2-VASc and HAS-BLED were 5.0  1.3 and 3.1  0.9, respectively. Oral anticoagulation (OAC) was initiated in 74 (26.5 %) of the patients. Of all patients, 33 (11.8%) patients died in hospital. Of the remaining patients, 104 were followed over 13.8  17.5 months with 3.5  2.3 visits during follow-up. Rhythm control was attempted in 10 patients (9.6%). OAC was initiated in 37 patients (35.6 %). Fifty-nine (56.7%) patients reached the primary composite endpoint. Stroke/TIA (34.6%) and heart failure (49%) were common. Subgroup analysis revealed no significant differences in any of the endpoints between patients undergoing rhythm versus rate control and between patients under OAC compared with patients without OAC. INR at follow-up and TTR were 1.76  1.0 and 29.5%  37.8% in patients receiving VKA. Conclusion: In this real-world cohort of very elderly patients with AF, a rhythm control strategy and OAC treatment were chosen only in a minority of the cases. If OAC was initiated, most received VKAs with a poor TTR during follow-up. A high incidence of stroke/TIA was observed in patients with and without OAC. Further data are needed to define optimal treatment of AF in this particular patient group. Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

The incidence of atrial fibrillation (AF), the most common cardiac arrhythmia, is rapidly increasing due to the demographic development of the industrialized countries.1 Large population-based studies

The authors declare no conflicts of interest. * Address correspondence to Alexander Wutzler, MD, MA, Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail address: [email protected] (A. Wutzler). http://dx.doi.org/10.1016/j.jamda.2015.05.012 1525-8610/Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

have shown that very elderly patients show both the highest burden of AF as well as AF-related complications.1,2 Because of the demographic changes in the industrialized world, an increase of AF in the group of elderly and very elderly is expected in the next years. In 2050, the number of nonagenarians is expected to rise to more than 70 million worldwide. Yet, the treatment of the very elderly remains challenging because of altered pharmacokinetics and dynamics and the presence of relevant comorbidities.3 Only limited data exist on the clinical relevance of AF in patients aged

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A. Wutzler et al. / JAMDA xxx (2015) 1e4

89 years or older. Elderly patients are underrepresented in those clinical trials that lead to guideline conclusions for clinical treatment of AF and other cardiovascular disorders.4 Therefore, the general AF treatment and anticoagulation strategy that is recommended in actual guidelines may not be appropriate for the very elderly patients.5 Given the estimated rise of the proportion of elderly and very elderly persons in the industrialized countries with its huge impact on health care and economics,6 the knowledge of the clinical course and treatment of AF in nonagenarians is paramount. We sought to clarify these challenging questions using a large AF registry.

Methods From a local database (the Berlin Atrial Fibrillation [BAF] database) all patients aged 89 years or older were identified. The BAF database consists of 11,888 patients who presented to our university hospital center with AF between January 2001 and December 2014. Patients with hyperthyroidism, shock of any type, sepsis, known end-stage malignant disease, or severe trauma were excluded from the registry. The study complies with the Declaration of Helsinki and was approved by the ethics committee of the Charité-Universitätsmedizin Berlin. Informed consent was waived due to the observational character of the study. At baseline, stroke and bleeding risk was assessed using the CHA2DS2-VASc7 and HAS-BLED8 scores, respectively. Furthermore, type of AF, symptoms using New York Heart Association (NYHA) and European Heart Rhythm Association (EHRA) class, comorbidities, treatment strategy (rate versus rhythm control) and anticoagulant treatment (vitamin K antagonists [VKAs], direct oral anticoagulants [DOACs] or no anticoagulants) were assessed. A composite of stroke/ transient ischemic attack (TIA), thromboembolic events, major bleeding, and death was the primary endpoint. Follow-up visits were scheduled at the discretion of the treating physician but at least once a year. Stroke/TIA, thromboembolic events and major bleeding, presence of atrial fibrillation, new onset of heart failure and change of NYHA class, and bradyarrhythmia necessitating pacemaker implantation were secondary endpoints. Endpoints were assessed at scheduled and unscheduled visits during follow-up. Study results are presented as numbers and percentages for categorical variables or mean and SD for continuous variables. A Mann-Whitney U test (for skewed data) or t test were used for comparison of continuous variables, whereas a c2 test was used to analyze discrete variables. All analyses were performed using SPSS software version 22.0 (SPSS Inc., Chicago, IL) with a P value less than .05 considered to be statistically significant.

Results Baseline Results Of all patients who presented to our hospital center and were included in the BAF registry between January 2001 and December 2014 (n ¼ 11,888), 279 (2.3 %) were 89 years or older. Mean age was 92.0  2.7 years (range 89e108); characteristics are presented in Table 1. Patients’ baseline medication is listed in Table 2. Of all patients, 17.2% had first-diagnosed AF, 42.3% had paroxysmal AF, 9% had persistent AF, and 31.5% permanent AF. Patients initially presented with EHRA class I in 38.4% of the cases, class II in 49.5%, class III in 10.0%, and class IV in 2.0%. Rhythm control was attempted by electrical or pharmacological cardioversion in 37 (13.3%) of the patients. Baseline CHA2DS2-VASc and HAS-BLED were 5.0  1.3 and 3.1  0.9, respectively. In the baseline cohort, 231 patients had known

Table 1 Patients’ Baseline Characteristics No. of patients Age, y Male Body mass index Left ventricular ejection fraction, % Heart rate, min1 Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg CHA2DS2-VASc HAS-BLED Smoker EHRA EHRA class I EHRA class II EHRA class III EHRA class IV AF type First diagnosed AF Paroxysmal AF Persistent AF Permanent AF Comorbidities Hypertension CAD Prior myocardial infarction Peripheral arterial disease Heart failure Previous stroke or TIA Diabetes mellitus Hyperlipoproteinemia COPD Carcinoma Impaired renal function Hypothyroidism Cognitive dysfunction Depression Neurological disorder Rheumatoid arthritis

279 92.0  2.7 74 (26.5) 25.1  5.4 50  11.9 90  31.9 136.3  28 77  20.8 5.0  1.3 3.1  0.9 7 (0.4) 107 138 28 6

(38.4) (49.5) (10) (2.2)

48 118 25 88

(17.2) (42.3) (9) (31.5)

222 84 66 24 125 68 63 55 34 29 110 31 39 11 5 7

(79.6) (30.1) (23.7) (8.6) (44.8) (24.4) (22.6) (19.7) (12.2) (10.4) (39.4) (11.1) (14) (3.9) (1.8) (2.5)

AF, atrial fibrillation; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; EHRA, European Heart Rhythm Association; TIA, transient ischemic attack. Values are n (%) or mean  SD.

AF with an indication for oral anticoagulation (OAC). Of those patients, 74 (32%) were under OAC at the time of presentation. Follow-up Results Of all patients, 33 (11.8%) died in hospital after admission. Causes of death were (absolute numbers): acute coronary syndrome (5), stroke (2), heart failure (5), respiratory failure (4), infection (7), renal failure (2), unknown (4), sudden cardiac death (1), aortic stenosis (1), aortic aneurysm (1), or mamma carcinoma (1). Of the remaining patients, 104 were followed over 13.8  17.5 months with 3.5  2.3 visits during follow-up. In the follow-up group, rhythm control was attempted in 10 patients (9.6%). OAC was initiated in 37 patients (35.6 %); 29 patients received VKAs, 6 received factor Xa inhibitors, and 2 received a thrombin inhibitor. Fifty-nine (56.7%) patients reached the primary composite endpoint. Stroke/TIA (34.6%) and heart failure (49.0%) were common in the study cohort. Thirty-eight percent of the patients were in sinus rhythm during follow-up (Table 3). Patients presented in NYHA class I in 8.7%, in NYHA II in 23%, in NYHA III in 13.5%, and in NYHA IV in 3.8% during follow-up. Subgroup Analysis Subgroup analysis revealed no significant differences in any of the endpoints between patients undergoing rhythm versus rate control

A. Wutzler et al. / JAMDA xxx (2015) 1e4 Table 2 Patients’ Baseline Medication No. of patients Flecainide Beta-blocker Amiodarone Sotalol Verapamil Diltiazem Digitoxin Clopidogrel Aspirin ACEI ARB Dihydropiridine CCB Nitrate Statin Insuline L Thyroxine Diuretics Antidepressant Neuroleptics Levodopa Oral anticoagulants VKA Factor Xa inhibitor Direct thrombin inhibitor

279 1 191 12 2 8 4 44 36 152 145 41 50 28 72 20 41 139 11 2 4

(0.4) (68.5) (4.3) (0.7) (2.9) (1.4) (15.8) (12.9) (54.5) (52) (14.7) (17.9) (10) (25.8) (7.2) (14.7) (49.8) (3.9) (0.7) (1.4)

59 (21.1) 12 (4.3) 3 (1.1)

ACEI, angiotensin-converting-enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker. Values are n (%).

and between patients under OAC compared with patients without OAC (Table 4). International normalized ratio (INR) was significantly higher in patients treated with VKAs compared with patients without OAC. Time in therapeutic INR range (TTR) was 29.5%  37.8% in patients taking VKAs. Discussion Here we present the results of a study on the treatment and outcomes of AF in nonagenarians. Our data show a proportion of 2.3% of patients who presented between 2001 and 2014 and were included in the BAF registry who were 89 years or older. Among those, most (61.6 %) was symptomatic. Rate control was chosen as a treatment strategy in most of the cases (86.7%), although roughly two-thirds of the patients had paroxysmal or even firstdiagnosed AF. The presence of relevant comorbidities and concomitant medication may have mainly influenced this decision. Rate control was in most cases achieved with beta-blocking agents, which have in general fewer pro-arrhythmic effects compared with treatment with class I and III antiarrhythmics. 9,10 Furthermore, betablocker treatment seems feasible and considerably safe in the very elderly.10 Beta-blockers have been shown to be excellent agents for

Table 3 Outcome During Follow-up Outcome During Follow-up, n ¼ 104 Composite endpoint (stroke/TIA, SE, major bleeding, death) Stroke/TIA SE Major bleeding Death Sinus rhythm at follow-up PM implantation Heart failure PM, pacemaker; SE, systemic embolism. Values are n (%).

59 (56.7) 36 14 12 15 40 11 51

(34.6) (13.5) (11.5) (14.4) (38.5) (10.6) (49)

3

Table 4 Subgroup Analysis of Outcome During Follow-Up Compared Between Patient With Rate Versus Rhythm Control and Patients Under Anticoagulants Versus Patients Without an Oral Anticoagulant Rhythm Control, n ¼ 10

Rate Control, n ¼ 94

P Value

Composite endpoint Stroke/TIA SE Major bleeding Death Sinus rhythm at follow-up PM implantation Heart failure

6 (60) 3 (30) 3 (30) 1 (10) 3 (30) 5 (50) 1 (10) 4 (40) OAC n ¼ 37

53 (56.4) 33 (35.1) 11 (11.7) 11 (11.7) 12 (12.8) 35 (37.2) 10 (10.6) 46 (48.9) No OAC n ¼ 67

.83 .75 .11 .87 .14 .43 .95 .59

CHA2DS2VASc HAS-BLED Composite endpoint Stroke/TIA SE Major bleeding Death Sinus rhythm at follow-up PM implantation Heart failure VKA DOAC INR at follow-up Time in therapeutic range (INR 2e3)

5.0  1.6 2.9  0.72 21 (56.8) 13 (35.1) 6 (16.2) 5 (13.5) 8 (21.6) 17 (45.9) 2 (5.4) 18 (48.6) 29 (78.4) 8 (21.6) 1.76  1.0* 29.5  37.8*

5.0  1.4 3.2  1.0 38 (56.7) 23 (34.3) 8 (11.9) 7 (10.4) 7 (10.4) 23 (34.3) 9 (13.4) 32 (47.8) d d 1.26  0.4 5  17

.93 .19 1 .93 .54 .64 .12 .24 .2 .93 d d

Treatment of Nonagenarians With Atrial Fibrillation: Insights From the Berlin Atrial Fibrillation (BAF) Registry.

The objective of this study was to determine course and treatment of atrial fibrillation (AF) in nonagenarians. Incidence of AF increases with age. Du...
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