RACE 7 ACWAS: Delayed Cardioversion Effective for Recent-Onset AF

Daniel M. Keller, PhD

March 20, 2019

LISBON — After delaying cardioversion based on a "wait-and-see" (WAS) approach for recent onset, symptomatic atrial fibrillation (AF) was just as good as acute cardioversion (AC) in getting patients back into sinus rhythm, assessed at 4 weeks, a noninferiority trial has shown.

Such patients usually undergo immediate pharmacologic or electrical cardioversion in the emergency department (ED) to restore sinus rhythm.

But because AF often stops spontaneously, the Rate Control versus Electrical Cardioversion Trial 7 – Acute Cardioversion versus Wait and See (RACE 7 ACWAS) asked the question of whether immediate restoration of sinus rhythm is really necessary for hemodynamically stable patients.

The trial randomly assigned patients with AF of up to 36 hours to either acute cardioversion or to rate-control medication alone. If in the delayed group the AF had not resolved within 48 hours, patients then received cardioversion.

"The wait-and-see strategy is noninferior to acute cardioversion in obtaining sinus rhythm in patients with symptomatic recent-onset atrial fibrillation, and it's associated with more spontaneous conversions and much lower need for unplanned acute cardioversions, similar, if not shorter, time spent in the emergency department, no safety concerns, and maintained quality of life," said Harry Crijns, MD, PhD, Cardiovascular Research Institute Maastricht and Maastricht University Medical Center, the Netherlands.

Crijns presented the findings here at the European Heart Rhythm Association 2019 Congress, and they were also published online March 18 in the New England Journal of Medicine.

Sinus Rhythm

The primary end point of the trial was achievement of sinus rhythm at 4 weeks. This open-label, Dutch multicenter trial would confirm noninferiority of WAS to acute cardioversion if the lower limit of the 95% confidence interval for the between-group difference in the primary end point in percentage points was greater than –10. End-point evaluation was done by observers blinded to the treatment group.

Patients coming to the ED were eligible for the trial if they had symptomatic AF that was documented by electrocardiogram (ECG) with a heart rate of at least 70 beats per minute (bpm) and were at least 18 years old. Among the exclusion criteria were hemodynamic instability (systolic blood pressure below 100 mm Hg; heart rate above 170 bpm), acute coronary syndrome, acute heart failure, Wolff–Parkinson–White syndrome or sick sinus syndrome, unexplained syncope, or persistent AF.

All eligible patients received antithrombotic therapy and were then randomized to the WAS (n = 218) or AC (n = 219) group.

WAS patients received rate-control drugs and were discharged with telemetric rhythm monitoring if they were in sinus rhythm or had AF of less than 110 bpm, with instructions to return the next day for ECG. If on the return visit they were in sinus rhythm, they were discharged and put on telemetric rhythm monitoring three times a day and told to return at 4 weeks for ECG.

If patients returned the next day for repeat ECG and were still in AF, they received cardioversion and, after stabilization, were discharged on the same telemetric monitoring and 4-week follow-up instructions.

After randomization to the AC group, patients received pharmacologic agents to try to return them to sinus rhythm. If that failed, they received electrical cardioversion and were discharged after stabilization to telemetric monitoring and 4-week follow-up for ECG.

The two groups of the trial were well balanced in terms of patient characteristics: mean age of 65 years, about 60% male, most with palpitations, a heart rate of around 124 bpm, about one-quarter with dyspnea, about one-quarter with chest pain, about 40% on an oral anticoagulant, and 21% to 24% on an antiarrhythmic drug. Notably, 62% to 66% of patients had a CHA2DS2VASC score of at least 2.

On the index visit of the WAS group (as close to 48 hours after symptom onset as possible), 69% had spontaneously returned to sinus rhythm, 4% received pharmacologic therapy and 24% electrical therapy for cardioversion, for a total of 97% of patients in sinus rhythm.

On their first visit to the ED, 94% of AC patients were converted to sinus rhythm, 40% by electrical cardioversion, 38% with pharmacologic management, and 16% spontaneously without cardioversion.

The total median duration of the index visit was 120 minutes for the WAS group (range, 60 to 253 min) and, for the AC group, was 158 minutes (range, 110 to 228 min). The 30-minute difference was statistically significant (95% CI, 6 - 51 min).

"Ninety-one percent of patients [were] in sinus rhythm at 4 weeks in the wait-and-see group and 94% in the acute cardioversion group," Crijns reported. "The between-group difference was –2.9%, which is [a] 95% confidence interval between –8.2 and 2.2, which is above the lower limit of –10%, which yields a value of .005 for noninferiority" of the WAS approach compared with AC.

Thirty percent of patients in each group had a recurrence of AF during the 4 weeks as assessed through telemetric monitoring (hazard ratio, 0.97). Over the 4 weeks, he said, "you can see that recurrences occur gradually over time."

Revisits to the ED during that time were 7% in both groups. Cardiovascular complications were very infrequent, both during the index visit and during follow-up. Two strokes occurred: one in each group at 5 and 10 days after the index visit. Quality-of-life measures did not differ between the groups.

Based on the study results, Crijns listed some advantages of the WAS approach.

"Cardioversion along with its potential complications may be avoided with a wait-and-see strategy," he said. "And also, the burden to the emergency department can be significantly reduced."

In addition, he noted that spontaneous conversions to sinus rhythm can occur, reducing the number of misclassifications of persistent AF, "enhancing appropriate rhythm control." Patients whose AF terminates by itself may recognize that they have more treatment options.

Clinically Relevant Question

Roy Beinart, MD, Sheba Medical Center, Ramat Gan, Israel, provided commentary on the study, calling the work "phenomenal," and the basis for it, comparing outcomes of the WAS and AC approaches, a "very simple and clinically relevant question."

He was concerned that at 4 weeks, three patients in each group had unstable angina or acute coronary syndrome, the reasons for which were not obvious.

He agreed with Crijns that the equivalence of outcomes in the two groups allows patients more opportunity for decision making "so that if a patient comes to the emergency room with atrial fibrillations... you can discuss with him several ways to approach his disorder."

Beinart concluded by raising a few open questions. The first was whether the WAS approach would be applicable to all centers, considering patient expectations, infrastructure, and costs. Then there is the issue of whether these results can be extrapolated to other patient populations, such as postpulmonary vein isolation, long-term recurrent paroxysmal AF, moderate to severe left atrial enlargement, valvular disorders, rheumatic heart disease, and octogenarians. He also wondered why there was a relatively high number of cases of acute coronary syndrome.

Jeff S. Healey, MD, McMaster University, Hamilton, Ontario, Canada, coauthored an editorial accompanying the RACE trial publication.

Commenting on the study for theheart.org | Medscape Cardiology, he said of the WAS approach: "More than to delay, it's to avoid [cardioversion], so approximately one in two patients in that study who were cardioverted in the acute cardioversion arm, if you look at the [WAS] group, would have spontaneously converted on their own without interventions. So you save a lot of resources, but also the risks of a general anesthetic and approximately half an hour on average of time spent in the emergency room."

He said the recurrence of AF among about one-third of patients in each group at 4 weeks is in keeping with the natural history of most AF, so neither the WAS or AC approach provided any long-term advantage over the other in terms of AF recurrence.

Healey said that both the study publication and the editorial make the point that the return scheduled visits to the ED within 2 days after discharge of the WAS patients were good because approximately half the patients who come into the ED for atrial fibrillation have been there before, "and I think the more attention we focus on ER management getting patients to proper follow-up care where things like anticoagulation, AF suppression, possibly ablation, but also risk factor management, can be addressed... this is better for the global treatment of patients rather than cardiovert and go home."

It is not reasonable to assume that once cardioversion has occurred and produced a sinus rhythm, a patient would continue in sinus rhythm for a long time, he added.

"I think what this [study] shows is the large number of people [who] are going to go back into atrial fibrillation if you don't do anything else. That is the point," Healey said. Although it was not a part of this trial, possibly better long-term management of patients could reduce the risk for AF re-emerging.

He noted that in the trial, the use of class Ic agents for cardioversion, as is done in the Netherlands, was quite effective, although for some patients going on to electrical cardioversion was required.

"I think this speaks to the broader issue: Should I even convert by any means in the first place?" he said. For these patients without previous persistent AF who are relatively early in the onset, "you could avoid cardioversion in one in two patients by simply waiting." However, what is required is a healthcare system that can see the patients again within 1 to 2 days to make the approach possible, he added.

Looking ahead from this study, Healey said, "I see this changing guidelines." Previous cardioversion studies raised concerns about the safety of cardioverting certain people with atrial fibrillation. "Here, that whole consideration is just out the window if we're not going to cardiovert them."

In the present study, he said all the patients were started on guideline-indicated antithrombotic therapy at the start of the trial "so you can avoid that concern about the risks and the perils of cardioversion entirely if you're not even cardioverting them."

He predicted that along with guideline changes, healthcare administrators "will be impressed" by less time spent attending to a patient in the emergency department and identical rates of return to the emergency department of only 7% of patients in both groups. So he foresees health economics will be an important driver of the WAS approach used in this trial.

The study was funded by the Netherlands Organization for Health Research and Development and others. Crijns and Beinart reported no disclosures. Healey reported grants and personal fees from BMS/Pfizer, Medtronic, and Boston Scientific, and personal fees from Servier.

N Engl J Med. Published online March 18, 2019. Full text, Editorial

European Heart Rhythm Association (EHRA) 2019 Congress: Abstract 800. Presented March 18, 2019.

 

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