Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation
Pluymaekers NAHA, Dudink EAMP, Luermans JGLM, et al.; RACE 7 ACWAS Investigators.
N Engl J Med. 2019 Apr 18;380(16):1499-1508. [Full text]
Visual Abstract @Visualmed
Summary by Andrew Hill
Treatment options for a recent onset (<36 hour) episode of atrial fibrillation include rate control or cardioversion, and this can be pharmacologic or electrical. On many occasions however, there is spontaneous conversion of atrial fibrillation to normal sinus rhythm suggesting a “wait-and-see” approach could be appropriate in some casses. The multicenter Race Control versus Electrical Cardioversion Trial 7 – Acute Cardioversion versus Wait and See (RACE 7 ACWAS) was published in early 2019 in the NEJM.
Adults (age >18) presenting to the emergency department with symptomatic, recent onset (<36 hour), hemodynamically stable atrial fibrillation were eligible. The study enrolled patients at 15 hospitals in the Netherlands. Exclusion criteria included hemodynamic instability (SBP <100, HR >170), signs of MI on ECG, presence of pre-excitation syndrome, history of sick sinus syndrome, history of unexplained syncope, history of persistent AF (>48h), or acute heart failure.
Patients were randomized 1:1 to early cardioversion, preferably with flecainide, versus a “wait-and-see” approach with rate control and outpatient follow up within 48 hours (“delayed-cardioversion”). In the delayed-cardioversion group, rate-control medications were used to achieve a heart rate < 110 beats per minute and relief of symptoms.
A total of 437 patients underwent randomization with 218 in the delayed-cardioversion group and 219 in the early-cardioversion group of which 212 and 215 respectively were included in primary analysis.
The average age was 65 +/- 11 years with 40% being female. 192 patients (44%) had their first episode of atrial fibrillation with palpitations (87%) being the most common presenting symptom. Upon presentation, 40% of patients were previously taking anticoagulation. The CHA2DS2-VASc score was ≥2 in most patients (62%).
The primary outcome was presence of sinus rhythm on ECG at 4 week follow up. Secondary outcomes included duration of index visit at the emergency department, emergency department visits related to atrial fibrillation, cardiovascular complications (events leading to ED visit or hospital admission – HF, ischemic stroke, TIA, unstable angina/ACS, symptomatic bradycardia/tachycardia, or hypotension), time until recurrence of atrial fibrillation, and quality of life as assessed by Atrial Fibrillation Effect on Quality-of-Life questionnaire (AFEQT).
Sinus rhythm on ECG at 4 week follow up was present in 91% (n=193) of patients in the delayed-cardioversion group versus 94% (n=202) in the early-cardioversion group. This had a group difference of negative 2.9 percentage points and assessed to be non-inferior (CI -8.2 to 2.2, p=0.005) using a cut off of negative 10 percentage points. In the delayed-cardioversion group, 69% (n=150) of patients spontaneously converted to sinus rhythm with 16% (n=36) in the early-cardioversion group.
With regards to secondary outcomes, the duration of the index visit was 120 minutes in the delayed cardioversion group (range, 60 to 253) vs 158 minutes (range, 110 to 228). Very few patients were admitted to the hospital (n=3 and n=5) and 7% of patients in both groups (n= 14 and n=14) had emergency department visits related to atrial fibrillation within the next 4 weeks.
Ten patients had cardiovascular complications in the delayed-cardioversion group and 8 patients in the early cardioversion group. Of the patients who participated in telemetry monitoring, recurrence of atrial fibrillation was similar at 4 weeks, 30% vs 29%. The time to event analysis was similar, HR 0.97, 95% CI, 0.65 to 1.43. If there was recurrence the median time was 12 days (range, 3 to 18) and 8 days (range, 2 to 18). Finally, quality of life assessed via the Atrial Fibrillation Effect on Quality-of-Life questionnaire (AFEQT) showed global scores of 72±19 in the delayed-cardioversion group and 73±19 in the early-cardioversion group (difference, −1 point; 95% CI, −5.3 to 4.0).
The authors concluded that a wait-and-see approach was non-inferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. Early cardioversion did shorten the time until conversion to sinus rhythm but did not increase overall number of patients who eventually converted. Also, a “wait-and-see” strategy was not more time consuming than early cardioversion nor were there more hospital admissions.
There is a theoretical benefit to earlier restoration of sinus rhythm and observational data has suggested sinus rhythm at discharge from the ED is associated with improved outcomes [1, 2], but this is not supported by RACE 7 ACWAS. Instead, the long term outcome can likely de better addressed by appropriate use of anti-coagulation and risk factor modification .
Of note, two of the centers utilized a systemic screening log while the majority of the centers enrolled patients without a screening log; this could have led to selection bias. Furthermore, around 100 patients were not included in the telemetry monitoring as there was a limit in the number of devices. Finally, there is the question of generalization of the findings to other regional areas, specifically the United States, immediate follow up (within 48 hours) can be limited and peri-cardioversion anesthetization is performed by the emergency department provider.
Since publishing in 2019, the findings have been included in the most recent update to the ESC guidelines  where both early and delayed pharmacologic or electrical cardioversion can be considered in atrial fibrillation within 48 hours. Early cardioversion remains an option for patients who have had atrial fibrillation for more than 36 hours if they are receiving long-term anticoagulation and/or are low risk for transesophageal echocardiography.
Finally, the ESC guidelines suggest utilizing an “Atrial fibrillation Better Care (ABC) holistic pathway (“A” – Anticoagulation/Avoid stroke; “B” – Better symptom management; “C” – Cardiovascular and Comorbidity). anticoagulation. It cannot be emphasized enough that stroke risk assessment should be considered in each patient, in addition to risk factor modification and establishing good follow up.
|F: Follow up||4 weeks|
|I: Intention to treat||Yes|
|S: Similar at baseline||Yes|
|E: Equal treatment||Not discussed / by design|
|S: Source (funding)||Netherlands Organization for Health Research and Development, Maastricht University Medical Center. Boehringer Ingelheim provided remote monitoring devices.|
- Stiell IG, Clement CM, Rowe BH, et al.; Outcomes for Emergency Department Patients With Recent-Onset Atrial Fibrillation and Flutter Treated in Canadian Hospitals. Ann Emerg Med. 2017 May;69(5):562-571.e2.
- Healey JS, McIntyre WF. The RACE to Treat Atrial Fibrillation in the Emergency Department. N Engl J Med. 2019 Apr 18;380(16):1578-1579.
- Hindricks G, Potpara T, Dagres N, et al.; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021 Feb 1;42(5):373-498. doi: 10.1093/eurheartj/ehaa612. PMID: 32860505.