Routine vs. Aggressive upstream rhythm Control for prevention of Early persistent atrial fibrillation in heart failure study - RACE 3

Contribution To Literature:

The RACE 3 trial showed that upstream risk factor modification was superior at maintaining sinus rhythm.


The goal of the trial was to evaluate upstream risk factor modification compared with conventional therapy among patients with early persistent atrial fibrillation.

Study Design

  • Randomized
  • Parallel

Patients with early persistent atrial fibrillation and heart failure were randomized to upstream therapy (n = 119) versus conventional therapy (n = 126).

Upstream therapy consisted of mineralocorticoid receptor antagonist, statin, angiotensin-converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker, and cardiac rehabilitation.

Inclusion criteria:

  • Early persistent atrial fibrillation and mild to moderate heart failure
  • Total atrial fibrillation history <5 years, total persistent duration >7 days but <6 months, and ≤1 electrical cardioversion
  • History of heart failure <1 year with preserved ejection fraction or left ventricular ejection fraction ≥45%
  • Total number of enrollees: 245
  • Duration of follow-up: 1 year

Principal Findings:

The primary outcome, incidence of sinus rhythm at 1 year, occurred in 75% of the upstream therapy group versus 63% of the conventional therapy group (p = 0.021).


Among patients with early persistent atrial fibrillation, upstream risk factor modification was effective at maintaining sinus rhythm at 1 year. Use of mineralocorticoid receptor antagonists, statins, ACE inhibitor and/or angiotensin receptor blockers, and cardiac rehabilitation can be considered in patients with persistent atrial fibrillation.


Rienstra M, Hobbelt AH, Alings M, et al. Targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent atrial fibrillation: results of the RACE 3 trial. Eur Heart J 2018;Feb 1:[Epub ahead of print].

Editorial: Pavlovic D, Kirchhof P, Fabritz L, et al. The RACE-3 is on: double-locking sinus rhythm by upstream and downstream therapy. Eur Heart J 2018;Feb 7:[Epub ahead of print].

Presented by Dr. Michiel Rienstra at the European Society of Cardiology Congress, Barcelona, Spain, August 27, 2017.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Nonstatins, Novel Agents, Statins, Acute Heart Failure

Keywords: Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Arrhythmias, Cardiac, Atrial Fibrillation, Cardiac Rehabilitation, ESC Congress, ESC2017, Heart Failure, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Mineralocorticoid Receptor Antagonists, Primary Prevention, Risk Factors

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