By Joshua D. Moss, MD
Associate Professor of Clinical Medicine, Cardiac Electrophysiology, Division of Cardiology, University of California, San Francisco
Dr. Moss reports he is a consultant for Biosense Webster and Abbott.
SYNOPSIS: Intermittent anticoagulation guided by continuous assessment of arrhythmia status in patients with low-to-moderate risk did not result in any strokes or thromboembolic events over a relatively short follow-up period.
SOURCE: Waks JW, et al. Intermittent anticoagulation guided by continuous atrial fibrillation burden monitoring using dual chamber pacemakers and implantable cardioverter-defibrillators: Results from the Tailored Anticoagulation for Non-Continuous Atrial Fibrillation (TACTIC-AF) pilot study. Heart Rhythm 2018 Jul 5. pii: S1547-5271(18)30593-9. doi: 10.1016/j.hrthm.2018.06.027. [Epub ahead of print].
Anticoagulation with warfarin or direct oral anticoagulants (DOACs) for prevention of stroke and other thromboembolic events is a cornerstone of therapy for atrial fibrillation (AF). Whether AF is associated with symptoms, and regardless of episode duration and frequency, anticoagulation is recommended based on presence of risk factors such as age, hypertension, diabetes, and congestive heart failure. However, chronic anticoagulation therapy comes with the cost of elevated bleeding risk. Waks et al hypothesized that in patients with low arrhythmia burden and relatively low thromboembolic risk, the continuous monitoring afforded by modern implantable pacemakers and defibrillators could facilitate “tailored anticoagulation.” Patients could start and stop anticoagulation based on AF burden, enabling protection from stroke and other thromboembolic events while reducing bleeding risks. This multicenter pilot study initially was designed as a randomized trial, with 1:1 assignment to standard therapy vs. tailored anticoagulation and 12 months follow-up. However, the control arm was removed after about two years to facilitate enrollment, and the trial continued as a single-arm prospective trial. Ultimately, 61 patients with a CHADS2 score ≤ 3 and a St. Jude pacemaker or ICD with a functioning atrial lead and capability for remote monitoring were enrolled at 10 centers in the United States. Patients had to have experienced at least one episode of AF but a “low” overall burden: < 30 minutes of total AF per day, and no continuous episodes lasting > 6 minutes.
For 48 patients, tailored anticoagulation therapy was used. After one month of mandatory anticoagulation, their DOAC was discontinued if no significant AF burden was present. Anticoagulation was restarted if biweekly remote monitoring revealed an episode of continuous AF > 6 minutes or a total burden of > 6 hours over a 24-hour period. Automatic transmissions for AF also were programmed for atrial rates > 200 bpm lasting > 30 minutes, and for total AF burden > 6 hours over a 24-hour period. For 13 patients who remained in a control arm, anticoagulation was continued, regardless of AF burden. Patients in the tailored therapy group averaged 71 years of age, 52% demonstrated a CHADS2 score of 2 and 35% a CHADS2 score of 1. During follow-up, these patients logged 3,763 total days on DOAC therapy after the first 30 days, out of 14,826 total monitored days. Due to protocol violations, 1,777 of those days on anticoagulation actually were “unnecessary.” There were two gastrointestinal bleeds in patients on anticoagulation and one fatal intracranial hemorrhage in a patient not on anticoagulation at the time. No strokes or transient ischemic attacks (TIAs) occurred. There were two episodes of epistaxis in the smaller control group. The authors concluded that this approach could certainly improve patient compliance and decrease cost and bleeding risk compared with continuous DOAC therapy.
In many ways, anticoagulation for thromboembolic prophylaxis in patients with AF has become considerably easier with the advent of DOACs. With fewer dietary and drug interactions than warfarin and no need for regular monitoring of therapeutic levels, the threshold for physicians to prescribe the medications and patients to take them has decreased. Nevertheless, anticoagulation for AF remains underused, and the added expense of DOACs compared with warfarin can be an obstacle. Additionally, bleeding risks remain an important consideration. It is possible that a tailored approach to anticoagulation could reduce the risk of thromboembolic events in a select group of patients to the same degree as daily chronic anticoagulation, while simultaneously reducing both bleeding risks and costs. This pilot study represents an important step toward demonstrating the feasibility of such an approach. Although it was underpowered to detect thromboembolic events, with an average of only 309 days of follow-up per patient, the lack of any strokes or TIAs was reassuring. There also were very few adverse events and a dramatic reduction in the use of anticoagulation, despite protocol violations at one study site, which resulted in many days of unnecessary therapy.
The principal weaknesses of the study are the sample size, the limited follow-up, and the lack of a true control group. Additionally, patients were required to have an implanted pacemaker or defibrillator with an atrial lead and remote monitoring capabilities, which limits the population for which this approach is currently applicable. Other studies have demonstrated the use of an implantable loop recorder to assess AF burden. However, additional data will be needed to test whether the cost of invasive monitoring is offset by the savings on drug therapy, confirm whether thromboembolic risk is adequately addressed, and assess whether there are fewer bleeding events or improved quality of life with tailored therapy.
Additionally, some prior studies have shown strokes and TIAs can occur without an apparent temporal relationship to periods of AF, suggesting that other nonarrhythmic factors (such as left atrial size and/or function) may play a role. For now, the safest approach for paroxysmal AF in patients with stroke risk factors likely remains chronic, uninterrupted anticoagulation, particularly considering the relatively low rates of serious or fatal bleeding events in trials of DOACs. However, as further trials are conducted and additional safety data gathered, tailored therapy may eventually prove to be a viable or even superior alternative.