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Kirchhof P, Camm AJ, Goette A, et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020 Oct 1;383(14):1305-1316. doi: 10.1056/NEJMoa2019422. Epub 2020 Aug 29. (Original study)
Abstract

BACKGROUND: Despite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control therapy can reduce this risk.

METHODS: In this international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial, we randomly assigned patients who had early atrial fibrillation (diagnosed =1 year before enrollment) and cardiovascular conditions to receive either early rhythm control or usual care. Early rhythm control included treatment with antiarrhythmic drugs or atrial fibrillation ablation after randomization. Usual care limited rhythm control to the management of atrial fibrillation-related symptoms. The first primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome; the second primary outcome was the number of nights spent in the hospital per year. The primary safety outcome was a composite of death, stroke, or serious adverse events related to rhythm-control therapy. Secondary outcomes, including symptoms and left ventricular function, were also evaluated.

RESULTS: In 135 centers, 2789 patients with early atrial fibrillation (median time since diagnosis, 36 days) underwent randomization. The trial was stopped for efficacy at the third interim analysis after a median of 5.1 years of follow-up per patient. A first-primary-outcome event occurred in 249 of the patients assigned to early rhythm control (3.9 per 100 person-years) and in 316 patients assigned to usual care (5.0 per 100 person-years) (hazard ratio, 0.79; 96% confidence interval, 0.66 to 0.94; P = 0.005). The mean (±SD) number of nights spent in the hospital did not differ significantly between the groups (5.8±21.9 and 5.1±15.5 days per year, respectively; P = 0.23). The percentage of patients with a primary safety outcome event did not differ significantly between the groups; serious adverse events related to rhythm-control therapy occurred in 4.9% of the patients assigned to early rhythm control and 1.4% of the patients assigned to usual care. Symptoms and left ventricular function at 2 years did not differ significantly between the groups.

CONCLUSIONS: Early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions. (Funded by the German Ministry of Education and Research and others; EAST-AFNET 4 ISRCTN number, ISRCTN04708680; ClinicalTrials.gov number, NCT01288352; EudraCT number, 2010-021258-20.).

Ratings
Discipline Area Score
Family Medicine (FM)/General Practice (GP) 7 / 7
General Internal Medicine-Primary Care(US) 7 / 7
Cardiology 6 / 7
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

I`m not sure that I see as much benefit to early rhythm control as the authors see. The excess number of people harmed by the therapy is nearly as many as the number of people who benefited from it, so I would be interested to see whether the benefit is still statistically significant if that is taken into account. The enrolled population is very restricted, which is evidenced by the fact that only an average of 20 patients per site were able to be enrolled over a five year period, so I wonder how generally applicable this information is to practice. Also, a significant number of people from the usual care group crossed over to rhythm control, and the article doesn`t say whether the analysis was by intention to treat, so I don`t know how this affects the results. Additionally, the article states that there was a decreased incidence of hospitalizations for CHF and ACS, but it appears from the Table that that may not be true since the CI crosses 1.

General Internal Medicine-Primary Care(US) rater

At this point, many physicians reflexively view rhythm control as no more effective than rate control. The AFFIRM study is the landmark study that forms the foundation of this opinion. From this article and the editorial, we see that the reality is more nuanced and depends on timing, whether ablation is part of the options, and what the other background treatments are. So, I think it's a good article for all clinicians to highlight that the situation has evolved and is not as simple as we once thought.

Hospital Doctor/Hospitalists rater

The benefit from rhythm control including ablation does not seem particularly dramatic (1 event/100 person-years). Also, since this research was done in European healthcare systems, it would be interesting to hear from qualified readers regarding how the benefits provided by a system of universal access to healthcare might impact what is "usual care" vs the US healthcare system, especially when contemplating applying the interventions of this paper to US clinical protocols.

Hospital Doctor/Hospitalists rater

This is an important study that showed superiority of rhythm control over rate control in early atrial fibrillation. Despite its limitations, the study adds data to the discussion about preferred strategy in the management of atrial fibrillation.
Comments from EvidenceAlerts subscribers

Dr. Frank Tyers (10/1/2020 3:08 PM)

Maintenance of an atrially based cardiac rhythm is optimal and should be continued as long as practical. However, an implanted pacemaker's electrogram recordings are often the only way to be sure you are actually successful, and the right atrial electrode should be low septal. Typical right-atrial appendage pacing actually increases inter-atrial conduction delay, so that in some patients LA and LV contraction are almost simultaneous. Then of course, a left atrial or adjacent focus will re-fibrillate regardless of drugs and or ablation. Many patients presenting with long interatrial conduction delays can be controlled for years with low-risk biatrial pacing to achieve atrial resynchronization, on its own or with a touch of Class I antiarrhythmic.