RACE 7 ACWAS

Published

Pluymaekers NAHA, et al. "Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation". The New England Journal of Medicine. 2019. 380(16):1499-1508.
PubMed • Full text • PDF • ClinicalTrials.gov

Clinical Question

In hemodynamically stable patients who present with new-onset atrial fibrillation within 36 hours, is delayed cardioversion at 48 hours non-inferior to early cardioversion for normal sinus rhythm at 4 weeks?

Bottom Line

In patients presenting with recent-onset symptomatic atrial fibrillation, delaying cardioversion until 48 hours after symptom onset was noninferior to early cardioversion in obtaining sinus rhythm after 4 weeks.

Major Points

Common clinical practice for patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation (AF) is to attempt early restoration of sinus rhythm through pharmacological or electrical cardioversion. However, it is well recognized that AF can spontaneously convert to sinus rhythm without intervention. An alternative "wait-and-see" approach has been proposed to reduce hospitalization and overtreatment.

Published in 2019, the Rate Control versus Electrical Cardioversion Trial 7–Acute Cardioversion versus Wait and See (RACE 7 ACWAS) randomized 437 patients presenting with recent-onset (<36 hours) symptomatic AF to early cardioversion or delayed cardioversion at 48 hours. In the early arm, cardioversion was preferably achieved pharmacologically (preferably via flecainide); electrical cardioversion was reserved for patients in which pharmacologic cardioversion was unsuccessful or contraindicated. In the delayed arm, patients were rate controlled to a heart rate (HR) <110 beats per minute (bpm) and discharged with follow-up scheduled ~48 hours from symptom onset. At this follow-up, the patient was referred to cardioversion if 12-lead ECG demonstrated ongoing AF. A subset of patients (~75%) were provided with a telemetric ECG device (MyDiagnostick) with instructions to use it three times daily and with recurrent symptoms to detect AF recurrences in the 4 weeks after the initial visit.

The primary endpoint of the study was maintenance of sinus rhythm, and this was measured via 12-lead ECG at an outpatient clinical follow-up 4 weeks after the incident visit. The proportion of patients in sinus rhythm was not different between the delayed (91%) compared to the early (94%) cardioversion groups. A secondary endpoint evaluated the recurrence of AF within the 4-week follow-up period. Neither the rate of AF recurrence nor the time to first AF recurrence were different between groups (30% delayed vs. 29% early recurrence rate; time-to-recurrence HR 0.97). Furthermore, visits to the emergency department due to recurrent AF were similar (7% in each group). The rates of successful conversion to sinus rhythm (either spontaneously or after pharmacologic ± electrical cardioversion) were similar between the two groups (97% delayed vs. 95% early). Notably, about two thirds of participants in the delayed arm spontaneously converted to sinus rhythm, compared to 18% in the early arm.

The study concludes that among patients presenting to the emergency department with recent onset, symptomatic AF, a wait-and-see approach is noninferior to early cardioversion at achieving sinus rhythm at 4 weeks.

Guidelines

2020 ESC Guidelines

• Guidelines acknowledge delayed and early cardioversion as acceptable approaches to managing atrial fibrillation within 48 hours of onset, depending upon the clinical circumstances.

Design

• Multicenter, randomized, open-label, non-inferiority trial
• N=437 patients with new-onset symptomatic AF
  • Delayed-cardioversion (n=218)
  • Early-cardioversion (n=219)
• Setting: 15 centers in the Netherlands
• Enrollment: 2014-2018
• Mean follow-up: 4 weeks
• Analysis: Non-inferiority of delayed compared to early cardioversion
• Primary Outcome: Presence of normal sinus rhythm at 4 weeks

Population

Inclusion Criteria

• Age >18 years
• Atrial fibrillation demonstrated on ECG
• Heart rate >70 bpm
• Presenting symptom(s) most likely due to AF
• Symptom duration <36 hours
• Able and willing to use a telemetric rhythm recorder, in this study the MyDiagnostic® device

Exclusion Criteria

• Hemodynamic instability, defined as either:
  • Systolic BP <100 mmHg
  • Heart rate >170 bpm
• Evidence of MI on ECG
• Presence of pre-excitation syndrome
• A history of sick sinus syndrome
• A history of unexplained syncope
• A prior AF episode lasting >48 hours
• Acute heart failure

Baseline Characteristics

From the delayed groups.

• Demographics
  • Age: 65±11 years
  • Female: 40%
  • Medical History
    • Hypertension: 54%
    • Diabetes: 10%
    • Myocardial infarction: 11%
    • Ischemic stroke or TIA: 6%
  • Medication use:
    • Vitamin K antagonist: 16%
    • Non-vitamin K oral anticoagulant: 26%
    • Antiarrhythmic drug: 21%
  • CHA₂DS₂-VASc Score
    • 0: 17%
    • 1: 22%
    • ≥2: 62%
• Presenting symptoms
  • Palpitations: 86%
  • Exercise-induced fatigue: 55%
  • Dyspnea: 26%
  • Chest pain: 25%
• Median HR during AF: 123 bpm

Interventions

• Randomization in a 1:1 ratio to delayed or early cardioversion
• Delayed cardioversion:
  • Rate control of heart rate <110 bpm with beta-blockers, non-dihydropyridine calcium channel blockers, or digoxin
  • Once deemed clinically stable, discharged with follow-up ~48h from onset of symptoms
  • At follow-up visit, if atrial fibrillation still present underwent cardioversion
• Early cardioversion:
  • Pharmacological (preferably with flecainide)
  • Electrical if pharmacological was contraindicated or unsuccessful

Outcomes

Comparisons are delayed vs. darly cardioversion.

Primary Outcomes

Sinus rhythm demonstrated on ECG 4 weeks after the incident visit

91% vs. 94% (between-group difference −2.9%; 95% CI −8.2-2.2; P=0.005)

Secondary Outcomes

Recurrence of AF within 4-weeks

30% vs. 29%

Time to recurrence of AF

Similar between groups (delayed HR 0.97; 95% CI 0.65-1.43)

Duration of the index visit

120 vs. 158 minutes (estimate for median difference 30 minutes, 95% CI 6 - 51)

Recurrent visit to the emergency department due to AF

7% in each group

Quality of life

Assessed via the Atrial Fibrillation Effect on Quality-of-Life questionnaire (AFEQT). Scores ranged from 0 to 100, higher scores indicating better quality of life

72±19 vs. 73±19 points (difference −1 point; 95% CI −5.3 - 4.0)

Cardiovascular complications

During either the index visit or 4-weeks of follow-up. Included Heart Failure; Ischemic stroke or transient ischemic attack; Unstable angina or acute coronary syndrome; Tachycardia, bradycardia or hypotension

10 vs. 8 complications

Criticisms

• Follow-up at 48 hours as an outpatient to reassess presence of AF may be challenging in some settings
• The early cardioversion group had a shortened time until sinus conversion was achieved. The time spent in AF correlates with the risk of thromboembolic sequelae. It is therefore conceivable that the delayed approach increases the risk thromboembolic sequelae. While there was not a difference in the rate of cardiovascular complications (including stroke/TIA), the study was not sufficiently powered for this assessment.
• Surveillance of recurrent AF was limited by intermittent telemetric assessment and likely underreported the true incidence.

Funding

• Netherlands Organization for Health Research and Development–Health Care Efficiency Research Program Grant 837002524
• Maastricht University Medical Center
• Boehringer Ingelheim provided some of the remote monitoring devices.