Intermittent vs. Continuous Anticoagulation theRapy in patiEnts with Atrial Fibrillation (iCARE-AF): a randomized pilot study

PurposeWe hypothesized that intermittent anticoagulation based on daily rhythm monitoring using the novel oral anticoagulants (NOACs) is feasible and safe among patients with paroxysmal atrial fibrillation (AF).MethodsPatients with paroxysmal AF and ≥1 risk factors for stroke were randomized to either intermittent or continuous anticoagulation. Those in the intermittent group were instructed to transmit a daily ECG using an iPhone-based rhythm monitoring device. If AF was detected, patients received one of the NOACs for 48 h–1 week. Patients who failed to transmit an ECG for three consecutive days or more than 7 days total were crossed over to continuous anticoagulation. Patients in the continuous group received one of the NOACs.ResultsFifty-eight patients were randomized to either intermittent (n = 29) or continuous anticoagulation (n = 29). Over a median follow-up of 20 months, 20 patients in the intermittent group failed to submit a daily ECG at least once (median three failed submissions). Four patients (14 %) crossed over to continuous anticoagulation due to failure to submit an ECG for three consecutive days. One stroke (continuous group) occurred during the study. Major bleeding occurred in two patients in the continuous and one patient in the intermittent group, after crossing over to continuous anticoagulation. In a prespecified per-protocol analysis, gastrointestinal bleeding was more frequent in the continuous group (16 vs. 0 %; p = 0.047).ConclusionsIntermittent anticoagulation based on daily rhythm monitoring is feasible and may decrease bleeding in low-risk patients with paroxysmal AF. A larger trial, adequately powered to detect clinical outcomes, is warranted.

[1]  E. Antman,et al.  Edoxaban versus warfarin in patients with atrial fibrillation. , 2013, The New England journal of medicine.

[2]  Jinkwon Kim,et al.  Stroke mechanism in patients with non‐valvular atrial fibrillation according to the CHADS2 and CHA2DS2‐VASc scores , 2012, European journal of neurology.

[3]  D. Euler,et al.  The effect of atrial pacing therapies on atrial tachyarrhythmia burden and frequency: results of a randomized trial in patients with bradycardia and atrial tachyarrhythmias. , 2003, Journal of the American College of Cardiology.

[4]  A. Capucci,et al.  Presence and Duration of Atrial Fibrillation Detected by Continuous Monitoring: Crucial Implications for the Risk of Thromboembolic Events , 2009, Journal of cardiovascular electrophysiology.

[5]  Dongfeng Qi,et al.  The Relationship Between Daily Atrial Tachyarrhythmia Burden From Implantable Device Diagnostics and Stroke Risk: The TRENDS Study , 2009, Circulation. Arrhythmia and electrophysiology.

[6]  F. Morady,et al.  Short-term effect of atrial fibrillation on atrial contractile function in humans. , 1999, Circulation.

[7]  Mukul Sharma,et al.  Evaluation of patients’ attitudes towards stroke prevention and bleeding risk in atrial fibrillation , 2013, Thrombosis and Haemostasis.

[8]  Daniel E. Singer,et al.  Device-detected atrial fibrillation and risk for stroke: an analysis of >10 000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices) , 2013, European heart journal.

[9]  W. Nelson,et al.  Impact of Daily Dosing Frequency on Adherence to Chronic Medications Among Nonvalvular Atrial Fibrillation Patients , 2012, Advances in Therapy.

[10]  Christopher E Hilker,et al.  Temporal relationship of atrial tachyarrhythmias, cerebrovascular events, and systemic emboli based on stored device data: a subgroup analysis of TRENDS. , 2011, Heart rhythm.

[11]  H. Sievers,et al.  Atrial Fibrillation Burden Estimates Derived from Intermittent Rhythm Monitoring are Unreliable Estimates of the True Atrial Fibrillation Burden , 2014, Pacing and clinical electrophysiology : PACE.

[12]  A. Natale,et al.  Initial real world experience with a novel insertable (Reveal LinQ(@Medtronic)) compared to the conventional (Reveal XT(@Medtronic)) implantable loop recorder at a tertiary care center - Points to ponder! , 2015, International journal of cardiology.

[13]  J Crowley,et al.  Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. , 1999, Statistics in medicine.

[14]  G. Breithardt,et al.  Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial , 2014, European heart journal.

[15]  Prashanthan Sanders,et al.  The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. , 2016, European heart journal.

[16]  Y. Chun,et al.  Incidence of Stroke or Systemic Embolism in Paroxysmal Versus Sustained Atrial Fibrillation: The Fushimi Atrial Fibrillation Registry , 2015, Stroke.

[17]  R. Simon,et al.  Optimal two-stage designs for phase II clinical trials. , 1989, Controlled clinical trials.

[18]  Hugh Calkins,et al.  2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. , 2014, Journal of the American College of Cardiology.

[19]  P. Sanders,et al.  Performance of a new atrial fibrillation detection algorithm in a miniaturized insertable cardiac monitor: Results from the Reveal LINQ Usability Study. , 2016, Heart rhythm.

[20]  W. Manning,et al.  Impaired left atrial mechanical function after cardioversion: relation to the duration of atrial fibrillation. , 1994, Journal of the American College of Cardiology.

[21]  R. Passman,et al.  Targeted Anticoagulation for Atrial Fibrillation Guided by Continuous Rhythm Assessment With an Insertable Cardiac Monitor: The Rhythm Evaluation for Anticoagulation With Continuous Monitoring (REACT.COM) Pilot Study , 2016, Journal of cardiovascular electrophysiology.

[22]  Glenn Salkeld,et al.  Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies , 2014, Thrombosis and Haemostasis.

[23]  Alexander Parkhomenko,et al.  Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials , 2014, The Lancet.

[24]  G. Lip,et al.  Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices. , 2015, European heart journal.

[25]  Apixaban versus Warfarin in Patients with Atrial Fibrillation , 2012 .

[26]  D. Singer,et al.  Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. , 2001, JAMA.

[27]  B. Gersh,et al.  Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial. , 2013, European heart journal.

[28]  S. Barold,et al.  Diagnosis of Paroxysmal Atrial Fibrillation in Patients with Implanted Pacemakers: Relationship to Symptoms and Other Variables , 2009, Pacing and clinical electrophysiology : PACE.

[29]  J. Reiffel.  If it were only that simple. , 2016, European heart journal.

[30]  Jonathan W. Waks,et al.  Role of atrial fibrillation burden in assessing thromboembolic risk. , 2014, Circulation. Arrhythmia and electrophysiology.

[31]  G. Breithardt,et al.  Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. , 2011, The New England journal of medicine.

[32]  F. Violi,et al.  Impact of new oral anticoagulants on gastrointestinal bleeding in atrial fibrillation: A meta-analysis of interventional trials. , 2015, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[33]  P. Sanders,et al.  Effect of atrial fibrillation on atrial thrombogenesis in humans: impact of rate and rhythm. , 2013, Journal of the American College of Cardiology.

[34]  Leon Poller,et al.  Dabigatran versus warfarin in patients with atrial fibrillation. , 2009, The New England journal of medicine.

[35]  A. Kadish,et al.  Course of Intraatrial Thrombi Resolution Using Transesophageal Echocardiography , 2003, Echocardiography.

[36]  D. Levy,et al.  Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. , 1998, Circulation.

[37]  A. Capucci,et al.  Temporal Relationship Between Subclinical Atrial Fibrillation and Embolic Events , 2014, Circulation.

[38]  Michael Markl,et al.  Evaluating the Atrial Myopathy Underlying Atrial Fibrillation: Identifying the Arrhythmogenic and Thrombogenic Substrate , 2015, Circulation.

[39]  T. Ikeda,et al.  Time course for resolution of left atrial appendage stunning after catheter ablation of chronic atrial flutter. , 2003, Journal of the American College of Cardiology.

[40]  J. Halperin,et al.  Subclinical atrial fibrillation and the risk of stroke. , 2012, The New England journal of medicine.

[41]  Massimo Santini,et al.  Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers. , 2005, Journal of the American College of Cardiology.