P6545Pacing as new predictor for atrial high rate episodes in patients with dual-chamber pacemakers and no history of atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Benezet Mazuecos ◽  
A Devesa Arbiol ◽  
C S Garcia Talavera ◽  
J A Iglesias ◽  
E Serrano ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Events ◽  
Pacemaker Implantation ◽  
High Rate ◽  
Prior History ◽  
Dual Chamber ◽  
Cardiac Implantable Electronic Devices ◽  
History Of ◽  
Dual Chamber Pacemakers

Abstract Introduction Both atrial and ventricular pacing (AP/VP) have been related to a higher risk of clinical atrial fibrillation (AF) documented on ECG. Subclinical AF is detected as atrial high rate episodes (AHRE) by cardiac implantable electronic devices and is related to a higher risk of stroke. Purpose The aim of this study was to determine whether the percentage of AP and/or VP in patients with pacemakers and no history of AF is related with the future development of subclinical AF (AHRE) and/or clinical AF (ECG documented). Methods From February 2012 to September 2015 we recruited patients with dual chamber pacemakers and no prior history of AF. Patients were followed at 3 months and every year then after. Subclinical AF, clinical AF and cardiovascular events were registered. AHRE (subclinical AF) was defined as an episode of atrial rate ≥225 bpm with a minimum duration of 5 min. Clinical AF was defined as ECG documented AF. Percentage of AP/VP was determined as the mean AP/VP during the first three visits. Mortality and cardiovascular events (including AF, stroke and hospitalization for heart failure) were also recorded. Results 249 patients (57% men; 75±9 years-old) were included. Mean time from pacemaker implantation was 9 months and the main indication was AV-block in 53% of the patients. Mean CHA2DS2-VASc score was 3.5±1.5. After a mean follow-up of 33±11 months, 38.5% of patients developed subclinical AF and 10.4% clinical AF. Patients with AP≥50% presented significantly higher risk of AHRE (62.5% vs 32.3%, OR 3.48; 95% CI [1.93–6.4] p<0.01) and clinical AF (18.7% vs 8.6%, OR 2.4; 95% CI [1.05–5.52] p<0.05). Patients with VP≥50% presented significantly higher risk of AHRE (46.4% vs 31.6%, OR 1.87; 95% CI [1.10–3.24] p<0.05) and clinical AF (25.9% vs 9.7%, OR 2.7; 95% CI [1.13–7.72] p<0.05). The percentage of AP and VP were not related to a higher risk of cardiovascular events or mortality. Multivariate analysis showed that AP≥50% was an independent predictor for AHRE (OR 2.4; 95% CI [1.19–4.97] p=0.014). Conclusions Pacing is related to a higher risk for developing subclinical and clinical AF in patients with dual-chamber pacemakers and no history of previous AF. Our data suggest, that patients presenting a high percentage of AP and VP should be closely followed during routinely pacemaker check-ups assessing for subclinical AF, especially in those with AP ≥50%.

Abstract 2648: Transient Atrial Fibrillation Within the First Month After Dual Chamber Pacemaker Implantation

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Suneet Mittal ◽  
Kenneth Stein ◽  
Shelly A Christman ◽  
Stacia Merkel ◽  
Timothy E Meyer ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Time Course ◽  
De Novo ◽  
Pacemaker Implantation ◽  
High Rate ◽  
Prior History ◽  
Dual Chamber ◽  
Long Term Follow Up ◽  
History Of ◽  
First Time

Background: Following pacemaker (PPM) implant, atrial fibrillation (AF) is often diagnosed for the first time based on detection of stored atrial high rate episodes (AHRE). However, there are no prospective data regarding the time course of developing AF following dual chamber PPM implantation. Methods: We evaluated data from the Silent Atrial Fibrillation Detection with Stored EGMs (SAFE) registry, which was a multi-center, prospective registry of patients undergoing dual chamber PPM implant. No patient had prior history of AF . Device interrogations were performed at 2-week, 3-, 6-, and 12-months post-implantation. An AHRE was defined as an atrial rate ≥ 180 bpm lasting ≥ 5 minutes. Results: 1488 patients (55% male, 74 ± 12 years) underwent PPM implantation. During the first month, 47 (3.7%) patients were diagnosed with AF for the first time. In 33 (70%) of these 47 patients, AF lasted between 5 and 60 minutes. Overall, the mean duration of AF was 133 ± 276 minutes (range: 5.4 minutes – 22.9 hours). A majority (81%) of these early episodes occurred within the first 15 days of implant. Twenty-four (51%) of these 47 patients did not have AF beyond this first month. Patients who did and did not have AF beyond the first month were similar with respect to baseline demographics, the use of active versus passive atrial leads, duration of first AF event, and time to first AF episode (Table ). Conclusions: In the SAFE registry, nearly 4% of patients with no history of AF exhibited AF in the first 30 days after PPM implant, with a majority occurring within the first 15 days post-implant. However, half of these patients failed to have another AHRE after the first month. These ``transient” episodes of AF may represent proarrhythmia from atrial lead insertion, de novo AF, or simply first-detection AF that was previously silent. Long-term follow-up studies are needed to determine the clinical significance of these transient episodes. SAFE: Demographics Among Patients with AF within 30 Days of Implant

scholarly journals Atrial high‑rate episodes and risk of major adverse cardiovascular events in patients with dual chamber permanent pacemakers: a retrospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Da Lu ◽  
Ju-Yi Chen
Keyword(s):  
Cardiovascular Events ◽  
Cox Regression ◽  
Pacemaker Implantation ◽  
Composite Endpoint ◽  
High Rate ◽  
Major Adverse Cardiovascular Events ◽  
Dual Chamber ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
History Of

AbstractPatients with atrial high-rate episodes (AHRE) are at higher risk of major adverse cardiovascular events (MACE). The cutoff threshold for AHRE duration for MACE, with/without history of atrial fibrillation (AF) or myocardial infarction (MI), is unknown. A total of 481 consecutive patients with/without history of AF or MI receiving dual-chamber pacemaker implantation were included. The primary outcome was a composite endpoint of MACE after AHRE ≥ 5 min, ≥ 6 h, and ≥ 24 h. AHRE was defined as > 175 bpm (MEDTRONIC) or > 200 bpm (BIOTRONIK) lasting ≥ 5 min. Cox regression analysis with time-dependent covariates was conducted. Patients’ mean age was 75.3 ± 10.7 years and 188 (39.1%) developed AHRE ≥ 5 min, 115 (23.9%) ≥ 6 h, and 83 (17.3%) ≥ 24 h. During follow-up (median 39.9 ± 29.8 months), 92 MACE occurred (IR 5.749%/year, 95% CI 3.88–5.85). AHRE ≥ 5 min (HR 5.252, 95% CI 2.575–10.715, P < 0.001) and ≥ 6 h (HR 2.548, 95% CI 1.284–5.058, P = 0.007) was independently associated with MACE, but not AHRE ≥ 24 h. Patients with history of MI (IR 17.80%/year) had higher MACE incidence than those without (IR 3.77%/year, p = 0.001). Significant differences were found between MACE patients with/without history of AF in AHRE ≥ 5 min but not AHRE ≥ 6 h or ≥ 24 h. Patients with dual-chamber pacemakers who develop AHRE have increased risk of MACE, particularly after history of AF or MI.

Prevalence of device-detected atrial fibrillation and stroke in patients with hypertrophic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Fumagalli ◽  
R Ruggieri ◽  
V De Filippo ◽  
F Cappelli ◽  
M Beltrami ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Hypertrophic Cardiomyopathy ◽  
De Novo ◽  
Multivariable Analysis ◽  
Prior History ◽  
Thromboembolic Events ◽  
Cardiac Implantable Electronic Devices ◽  
History Of ◽  
Ischemic Attack

Abstract Introduction Atrial fibrillation (AF) is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and is associated with adverse outcome, impaired quality of life, loss of productivity, and the risk for embolic stroke. However, still today, the real burden of AF is unresolved due to the unknown frequency of silent asymptomatic episodes. Purpose To assess the prevalence of device-detected AF and stroke in patients with HCM implanted with cardiac implantable electronic devices (CIEDs) at our institution, a long-standing high flow referral center for cardiomyopathies. Methods Clinical and instrumental data of HCM patients implanted with CIEDs (either pacemakers [PM] or implantable cardioverter defibrillator [ICD]) from 1998 to 2019 were retrospectively reviewed. Inclusion criteria were site-designated diagnosis of HCM, age at diagnosis &gt;18 years, &gt;1 follow up visit, follow up &gt;1 year. HCM phenocopies (e.g. Fabry disease) were carefully excluded. Patients were divided into three categories according to presence of AF (“AF prior to CIED implantation” vs “AF after CIED implantation” vs “no arrhythmia detected”). Outcome was measured against prevalence of thromboembolic events (stroke or transient ischemic attack [TIA]) at follow up. All-cause and cardiovascular (CV) mortality were also assessed. Results A total of 255 patients received a CIED (57% men, mean age at implantation 54±17 years). Men were younger at implantation (52±17 vs 56±18 years, p=0.022). At baseline, AF was present in 90 (35.3%) patients. During 5.0±4.1 years, de novo AF was detected in 30 (11.8%) individuals, resulting in an annual incidence rate of 6.1%/year. Overall, 135 (52.9%) of patients remained is sinus rhythm. Stroke/TIAs were reported in 30 (11.8%) patients: 16 (53.3%) occurred in patients with prior history of AF, 3 (10%) in patients with de novo AF (with men being at higher risk, OR 3.73, 95% CI 1.88–6.09, p=0.041), and 11 (36.7%) in patients with no history of arrhythmias. Long term, 45 (17.6%) patients died (CV mortality N=38, 14.9%). At multivariable analysis, history of stroke was directly related to all-cause mortality irrespective of AF in men (OR 4.15, 95% CI 1.35–12.77, p=0.018) but not in women (OR 0.891, 95% CI 0.17–4.64, p=0.801). Conclusions In a large cohort of consecutive high risk HCM patients referred to CIED implantation, the incidence of de-novo AF was high. Thromboembolic events were associated to worse outcome only in men, likely due to competing heart failure related causes in women. Strategies promoting early identification of AF and anticoagulation may play an important role in management and prevention of disease-related complications. Prevalence of AF and Stroke Funding Acknowledgement Type of funding source: None

Abstract 13274: Predictors of Mortality in Critically Ill Covid-19 Patients - A Multicenter Prospective Analysis of 159 Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Randy Ip ◽  
Zulfiqar Qutrio Baloch ◽  
manel boumegouas ◽  
Abdullah Al abcha ◽  
Steven Do ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Critically Ill ◽  
Demographic Data ◽  
Prior History ◽  
Multivariable Logistic Regression Analysis ◽  
Elevated Troponin ◽  
Ischemic Disease ◽  
Patient Status ◽  
History Of

Introduction: Certain patient demographics and biomarkers have been shown to predict survival in patients infected with COVID-19. However, predictors of outcome in patients who are critically ill and require advanced respiratory support are unclear. Methods: We performed a multicenter analysis of 159 consecutive patients with confirmed COVID-19 who were admitted to Intensive Care Unit (ICU) between March 01, 2020 and April 30, 2020. Patients were then followed until May 23, 2020. Demographic data (age, sex, race, BMI) and past medical history (hypertension, diabetes, COPD, CKD, history of cardiac ischemic disease, atrial fibrillation and heart failure) were recorded. Laboratory values (troponin, CPK, pro-BNP, ferritin, LDH and d-dimer) were analyzed. Patient status was classified as either alive or deceased at hospital discharge or the end of follow up period. Results: Mean patient age was 66+/-15 and 53% were male. Mean BMI was 31+/- 9. Mean hospital ICU stay was 11+/-8 days. Mortality rate of this ICU cohort at the end of follow-up was 63%. Fifty-five (34%) patients were discharged from the hospital. A multivariable logistic regression analysis identified four factors (age, prior history of diabetes, prior history of atrial fibrillation and elevated troponin) that had significant and independent contributions to the likelihood of survival. Each increase in decade of age above 40 (p = 0.010) was predicted to reduce survival by 30%, the presence of diabetes (p = 0.041) by 57%, a prior history of atrial fibrillation (p= 0.011) by 75%, and each increase of 0.1 ng/mL of troponin above 0.05 ng/ml (p = 0.001) by 55%. Conclusion: Mortality of critically ill COVID-19 patients is high. Early aggressive treatment of high-risk patients identified in this study (advanced age, history of diabetes and atrial fibrillation and elevated troponin) could improve clinical outcome. The highly predictive value of elevated troponin levels on survival may indicate cardiac involvement of COVID-19 infection as a determinant of mortality. Additionally, of available published literature at this time, this is the first study that suggests a relationship between atrial fibrillation and increased mortality from COVID-19. Larger studies are needed to confirm these findings.

scholarly journals Determinants of development of permanent atrial fibrillation and its treatment

EP Europace ◽  
1999 ◽  
Vol 1 (1) ◽  
pp. 35-39 ◽  
Author(s):  
L. Gianfranchi ◽  
M. Brignole ◽  
C. Menozzi ◽  
G. Lolli ◽  
N. Bottoni
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Risk Group ◽  
Pacemaker Implantation ◽  
Structural Heart Disease ◽  
High Risk Group ◽  
Symptom Duration ◽  
Permanent Atrial Fibrillation ◽  
History Of

Abstract We evaluated the rate of progression of permanent atrial fibrillation (AF) and identified clinical factors that predict this event in 63 consecutive patients who had undergone AV junctional ablation and DDDR pacemaker implantation for drug-refractory paroxysmal atrial fibrillation/flutter. Immediately after ablation, anti-arrhythmic drugs were discontinued in all cases. Permanent AF was con-sidered to have developed if AF was present on two consecutive 6-monthly examinations with no interim documented sinus rhythm. During a mean follow-up of 23±16 months, 22 (35%) of the 63 patients developed permanent AF. The actuarial estimate of progression of permanent AF was 22%, 40% and 56%, respectively, 1, 2 and 3 years after ablation. Age and underlying heart disease were independent predictors of progression of permanent AF. Only one (6%) of 16 patients with idiopathic AF had permanent AF (low risk group). Among the 47 patients with structural heart disease, permanent AF developed in 18 (62%) of the 29 who were aged >75 years or had >12 arrhythmic episodes per year and a symptom duration >4 years (high risk group), but only in three (17%) of the remaining 18 patients who did not (intermediate risk group). In conclusion, during a 3-year follow-up period, about half of the patients with a history of drug-refractory paroxysmal AF did not develop permanent AF after AV junctional ablation and dual-chamber pacemaker implantation, even in the absence of anti-arrhythmic drug therapy. Moreover, subgroups of patients whose risk of permanent AF progression differed were identified on the basis of simple baseline clinical variables. The results of this study form the necessary background for the correct management of patients after AV junction ablation and for the planning of future trials in this field.

scholarly journals Subclinical Atrial Fibrillation and Risk of Stroke: Past, Present and Future

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 611 ◽  
Author(s):  
AlTurki ◽  
Marafi ◽  
Russo ◽  
Proietti ◽  
Essebag
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Electronic Devices ◽  
High Rate ◽  
Cardiac Monitoring ◽  
Stroke Event ◽  
Cardiac Implantable Electronic Devices ◽  
Increased Risk ◽  
History Of ◽  
New Evidence

Subclinical atrial fibrillation (SCAF) describes asymptomatic episodes of atrial fibrillation (AF) that are detected by cardiac implantable electronic devices (CIED). The increased utilization of CIEDs renders our understanding of SCAF important to clinical practice. Furthermore, 20% of AF present initially as a stroke event and prolonged cardiac monitoring of stroke patients is likely to uncover a significant prevalence of SCAF. New evidence has shown that implanting cardiac monitors into patients with no history of atrial fibrillation but with risk factors for stroke will yield an incidence of SCAF approaching 30–40% at around three years. Atrial high rate episodes lasting longer than five minutes are likely to represent SCAF. SCAF has been associated with an increased risk of stroke that is particularly significant when episodes of SCAF are greater than 23 hours in duration. Longer episodes of SCAF are incrementally more likely to progress to episodes of SCAF >23 hours as time progresses. While only around 30–40% of SCAF events are temporally related to stroke events, the presence of SCAF likely represents an important risk marker for stroke. Ongoing trials of anticoagulation in patients with SCAF durations less than 24 hours will inform clinical practice and are highly anticipated. Further studies are needed to clarify the association between SCAF and clinical outcomes as well as the factors that modify this association.

scholarly journals 444 Epidemiology of subclinical atrial fibrillation in patients with cardiac implantable electronic devices: a systematic review and meta-regression

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Marco Borgi ◽  
Marco Proietti ◽  
Giulio Francesco Romiti ◽  
Marco Vitolo ◽  
Arianna Di Rocco ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Regression Analysis ◽  
Electronic Devices ◽  
Older Age ◽  
Cardiac Implantable Electronic Devices ◽  
History Of ◽  
Meta Regression ◽  
Meta Regression Analysis

Abstract Aims In recent years, attention to subclinical atrial fibrillation (SCAF), defined as the presence of atrial high-rate episodes (AHREs), in patients with cardiac implantable electronic devices (CIEDs), has gained much interest as a determinant of clinical AF and stroke risk. To perform a systematic review and meta-regression of the available scientific evidence regarding the epidemiology of SCAF in patients receiving CIEDs. Methods and results PubMed and EMBASE were searched for all studies documenting the incidence of AHREs in patients (n = 100 or more) with CIEDs without any previous history of AF from inception to 20 August 2021, screened by two independent blind reviewers. This study was registered in PROSPERO: CRD42019106994. Among the 2614 results initially retrieved, 54 studies were included, with a total of 72 784 patients. Meta-analysis of included studies showed a pooled prevalence of SCAF of 28.1%, with an incidence rate (IR) of 16 new SCAF cases per 100 patient-years (I2 = 100%). Multivariate meta-regression analysis showed that age and follow-up time were the only significant determinants of IR, explaining a large part of the heterogeneity (R2 = 61.5%, P &lt; 0.001), with higher IR at earlier follow-up and in older patients, decreasing over follow-up time and increasing according to mean age. Older age, higher CHA2DS2-VASc score, history of AF, hypertension, CHF, and stroke/TIA were all associated with SCAF occurrence. Conclusions In this systematic review and meta-regression analysis, IR of SCAF increased with age and decreased over longer follow-up times. SCAF was associated with older age, higher thromboembolic risk, and several cardiovascular comorbidities.

Abstract 225: Healthcare Burden Associated with Dyspepsia Among Nonvalvular Atrial Fibrillation Patients

2013 ◽  
Vol 6 (suppl_1) ◽  
Author(s):  
Michael H Kim ◽  
Kelly F Bell ◽  
Dinara Makenbaeva ◽  
Daniel Wiederkehr ◽  
Jay Lin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Baseline Period ◽  
Charlson Comorbidity Index Score ◽  
Prior History ◽  
Nonvalvular Atrial Fibrillation ◽  
Entire Study ◽  
Healthcare Burden ◽  
History Of ◽  
Study Population

Objective: To evaluate the annual healthcare burden associated with dyspepsia among nonvalvular atrial fibrillation (NVAF) patients Methods: NVAF patients ≥18 years of age with continuous medical/prescription coverage were identified (1/1/2007-12/31/2009) from the MarketScan ® Commercial and Medicare Research Databases. Patients with at least 1 inpatient or 2 outpatient dyspepsia diagnoses within 12 months following any NVAF diagnosis were grouped into the dyspeptic cohort, with patients without any dyspepsia diagnosis during the entire study period grouped into the non-dyspeptic cohort. The date of first dyspepsia diagnosis after NVAF diagnosis and a random date within 12 months after NVAF diagnosis were selected as the index dates for dyspeptic and non-dyspeptic patients, respectively. Baseline and follow-up periods were each 12 months. Of the overall dyspeptic and non-dyspeptic cohorts, patients were matched (1:1) by key patient characteristics. The dyspeptic cohort was further categorized as having a prior history of dyspepsia (chronic) or no dyspepsia (non-chronic) during the baseline period. Healthcare utilization and costs were evaluated and compared during the follow-up for matched cohorts. Results: Of 142,322 NVAF patients included in the overall study population (mean age: dyspeptic: 73.68, non-dyspeptic: 72.09 years, p<0.001), 10.2% were diagnosed with dyspepsia, with 67% of them having no history of prior dyspepsia during the baseline. Among the matched study population (N=28,172), patients had similar baseline characteristics: mean Charlson Comorbidity Index score of 2.3 in both cohorts and mean CHADS 2 scores of 1.9 and 1.8 for the non-dyspeptic and dyspeptic cohort, respectively. During the follow-up period, healthcare resource utilization and related costs were significantly greater for the dyspeptic cohort vs. the non-dyspeptic cohort (Table). Patients with chronic dyspepsia were the least likely to receive warfarin in the follow-up period (non-dyspeptic: 57.2%, non-chronic: 50.4%, chronic: 46.6%, p<0.001). Conclusions: NVAF patients with dyspepsia used healthcare resources to a greater extent and had greater healthcare costs than NVAF patients without dyspepsia. Warfarin usage appeared to be lower among NVAF patients with dyspepsia.

scholarly journals Characteristics of Apixaban-Treated Patients, Evaluation of the Dose Prescribed, and the Persistence of Treatment

2018 ◽  
Vol 23 (6) ◽  
pp. 494-501 ◽  
Author(s):  
Ainhoa Gomez-Lumbreras ◽  
Jordi Cortes ◽  
Maria Giner-Soriano ◽  
M. Angeles Quijada-Manuitt ◽  
Rosa Morros
Keyword(s):  
Atrial Fibrillation ◽  
Primary Care ◽  
Factor Xa ◽  
Recommended Dose ◽  
Prior History ◽  
Nonvalvular Atrial Fibrillation ◽  
Treatment Naïve ◽  
History Of ◽  
Using Data

Background: Apixaban is a direct oral anticoagulant, which inhibits factor Xa. It has demonstrated clinical efficacy in prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation and a better safety profile compared to warfarin. Objectives: (1) To describe the characteristics of patients with nonvalvular atrial fibrillation beginning treatment with apixaban, (2) to analyze concomitant prescriptions of medications that could potentially interact with apixaban, (3) to evaluate the level of appropriate usage according to the recommended dosage, and (4) to estimate the level of apixaban persistence among naive and non-naive patients. Methods: Cohort study using data from primary care (System for Research in Primary Care database, users of the Institut Català de la Salut; Catalonia, Spain) from August 2013 to December 2015. Results: Mean age for apixaban-treated patients was 71.8 years (standard deviation = 11.1) and 55.6% were male. In all, 3.2% of patients receiving apixaban were taking drugs described as potentially related to either pharmacokinetic or pharmacodynamic interactions. According to the summary of product characteristics, 81.1% of patients with a recommended dose of 2.5 mg twice daily and 51.8% with a recommended dose of 5 mg twice daily actually took this dose. After 1 year of follow-up, 62.6% of the apixaban users showed good adherence. Conclusion: The prescribed dose of apixaban did not fully follow the recommended dose, particularly in patients who were treatment naive. Patients with a prior history of anticoagulant treatment were more likely to remain persistent to treatment with apixaban.

Atrial Fibrillation in CLL/SLL Patients on Ibrutinib

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2933-2933 ◽  
Author(s):  
Mohammed Farooqui ◽  
Janet Valdez ◽  
Susan Soto ◽  
Amanda Bray ◽  
Xin Tian ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
General Population ◽  
Incidence Rate ◽  
Single Agent ◽  
Bleeding Complications ◽  
Prior History ◽  
History Of ◽  
Previously Treated ◽  
Grade 3

Abstract INTRODUCTION: Ibrutinib is approved for treatment (tx) of CLL in patients (pts) with previously treated disease and CLL with deletion (del) 17p. It has shown substantial improvements in progression free survival (PFS) and overall survival (OS) with a tolerable safety profile. Atrial fibrillation (Afib) has been observed in pts treated with ibrutinib, particularly in pts with cardiac risk factors, acute infections, and history of Afib. In the RESONATE study 3% of pts on ibrutinib developed Afib (median follow-up (f/u) 8.6 months (mo)) while 1% of pts on ofatumumab (median f/u 5.3 mo) developed Afib. Here we assessed the incidence of Afib in an independent cohort of pts with long f/u enrolled in our investigator-initiated trial of single agent ibrutinib. PATIENTS AND METHODS: This phase II trial (NCT01500733) enrolled 86 pts (Cohort 1: ≥ 65 years old (yo) without del 17p (n=35); Cohort 2: ≥ 18 yo with presence of del 17p (n=51)) who were treated with ibrutinib 420 mg daily continuously. Treatment-naive and previously treated pts in need of treatment (tx) were eligible. Safety data for Afib was compiled on all pts who received tx. All pts who developed Afib (per patient report or incidental finding) stopped ibrutinib therapy and underwent a cardiology evaluation which may have included an echocardiogram, stress test, and/or holter monitor at the discretion of the evaluating cardiologist. The annualized exposure adjusted incidence rate of Afib was estimated and compared between subgroups. RESULTS: At a median follow-up of 28 mo, 14 (16%) of 86 patients were found to have Afib while on study, 11 pts were ≥65 yo; 3 pts < 65 yo. In 9 (10%) pts this was the first recorded event, while 5 (6%) had a prior history of Afib. One patient developed Afib during pneumonia and in all other pts no contributing factors were identified. The median time to the first event on study was 18.24 (IQR: 10.8-26.0) mo. The annualized incidence was 0.052 (95% CI, 0.024- 0.099) events per person-year of treatment exposure among pts (n=81) without a prior history of Afib, 0.061 (95% CI: 0.025-0.126) in pts ≥65 yo (n=52), and 0.035 (95% CI: 0.004-0.125) in pts <65 yo (n=29, P =0.43 for difference in incidence based on age). In 11 (79%) of 14 pts Afib was grade 2, and in 3 (21%) grade 3. The grade 3 events required hospitalization and control of Afib through intravenous medications. All 3 pts had resolution of Afib and completed cardiology evaluation prior to restarting ibrutinib at a lower dose (280 mg), one received only aspirin (ASA) 81 mg, one received ASA 81 mg and an antiarrhythmic (sotalol), and one patient was anticoagulated with apixaban. Of 11 pts with grade 2 events, 6 (55%) pts currently do not have any symptoms or EKG findings of Afib, 3 (27%) pts intermittently have symptoms or EKG findings of Afib, and 2 (18%) pts have ongoing Afib. All of these 11 pts restarted ibrutinib at the same dose (420 mg); 5 received ASA 81 mg, 2 were on dabigatran transiently and then continued ASA 81 mg, and the other 4 pts started apixiban. F/u on apixiban ranges from 7-17 mo with no bleeding-related adverse events grade >1. CONCLUSION: The rate of Afib in this study at 16% is higher than previously reported, likely due to longer f/u. Indeed, the estimated Afib rate at 17 mo in RESONATE was 5.1%, similar to 5.6% at the same timepoint in our study. The annualized incidence rate of Afib in our study at 0.052 (95% CI, 0.024- 0.099) is higher than the estimated rate of 0.0124 per person-year in the general population (Schnabel et al, Lancet 2015). Given that the rate of Afib is higher in illness, longer follow-up in randomized studies will be needed to distinguish disease from drug-related factors. Notably, none of our pts had to discontinue ibrutinib because of Afib. Furthermore, there is currently no evidence that the severity of Afib in pts on ibrutinib differs from the general population. Given that the majority of our patients have del 17p and/or previously treated disease we feel that the risk-benefit profile favors continued ibrutinib treatment. In a small number of pts and with limited duration of observation we have not noted any serious bleeding complications in pts on ibrutinib and concurrent apixaban or 81 mg ASA. Research supported by the Intramural Research Program of NHLBI. We thank our patients for participation. We acknowledge Pharmacyclics for providing study drug. Disclosures Wiestner: Pharmacyclics: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document