Paulus Kirchhof1, A John Camm1, Andreas Goette1, Axel Brandes1, Lars Eckardt1, Arif Elvan1, Thomas Fetsch1, Isabelle C van Gelder1, Doreen Haase1, Laurent M Haegeli1, Frank Hamann1, Hein Heidbüchel1, Gerhard Hindricks1, Josef Kautzner1, Karl-Heinz Kuck1, Lluis Mont1, G Andre Ng1, Jerzy Rekosz1, Norbert Schoen1, Ulrich Schotten1, Anna Suling1, Jens Taggeselle1, Sakis Themistoclakis1, Eik Vettorazzi1, Panos Vardas1, Karl Wegscheider1, Stephan Willems1, Harry J G M Crijns1, Günter Breithardt1. 1. From the Department of Cardiology, University Heart and Vascular Center (P.K.), and Institute of Medical Biometry and Epidemiology (A.S., E.V., K.W.), University Medical Center Hamburg-Eppendorf, LANS Cardio (K.-H.K.), and the Department of Cardiology, Asklepios Klinik St. Georg (S.W.), Hamburg, Atrial Fibrillation Network (AFNET) (P.K., A.G., L.E., T.F., D.H., K.-H.K., N.S., U.S., J.T., K.W., S.W., G.B.) and the Department of Cardiology II (Electrophysiology), University Hospital Münster (L.E., G.B.), Münster, the German Center of Cardiovascular Research, Partner Site Hamburg/Lübeck/Kiel (P.K., K.W., S.W.), St. Vincenz Hospital, Paderborn (A.G.), the Working Group of Molecular Electrophysiology, University Hospital Magdeburg, Magdeburg (A.G.), the Clinical Research Institute, Munich (T.F.), Hospital Konstanz, Konstanz (F.H.), the Department of Cardiology and Electrophysiology, University Heart Center-Helios, and Leipzig Heart Institute, Leipzig (G.H.), University Heart Center Schleswig-Holstein, Campus Lübeck, Lübeck (K.-H.K.), Cardiology Practice Schön, Mühldorf (N.S.), and Cardiology Practice Taggeselle, Markkleeberg (J.T.) - all in Germany; the Institute of Cardiovascular Sciences, University of Birmingham, Birmingham (P.K.), the Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St. George's University of London, London (A.J.C.), and the Department of Cardiovascular Sciences, University of Leicester, National Institute for Health Research Leicester Biomedical Research Centre, Glenfield Hospital, Leicester (G.A.N.) - all in the United Kingdom; the Department of Cardiology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense (A.B.); Isala Hospital and Diagram B.V., Zwolle (A.E.), the University of Groningen, University Medical Center Groningen, Groningen (I.C.G.), and the Department of Physiology, Cardiovascular Research Institute Maastricht (U.S.), and the Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht (H.J.G.M.C.), Maastricht - all in the Netherlands; University Hospital Zurich, Zurich (L.M.H.), and the Division of Cardiology, Medical University Department, Kantonsspital Aarau, Aarau (L.M.H.) - both in Switzerland; University Hospital Antwerp and Antwerp University, Antwerp, Belgium (H.H.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (J.K.); the Hospital Clinic, University of Barcelona and Institut de Recerca Biomèdica, August Pi-Sunyer, Barcelona (L.M.), and Centro Investigación Biomedica en Red Cardiovascular, Madrid (L.M.); Department of Cardiology, Hospital Wojewódzka Stacja Pogotowia Ratunkowego i Transportu Sanitarnego (WSRiTS) Meditrans, Warsaw, Poland (J.R.); the Department of Cardiology, Ospedale dell'Angelo, Venice, Italy (S.T.); and Heart Sector, Hygeia Hospitals Group, Athens (P.V.).
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 eitherearly 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.).
RCT Entities:
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.).
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