Title of Trial
A Comparison of Rate Control and Rhythm Control in Patients With Recurrent Persistent Atrial Fibrillation (RACE)

Date and Citation of Primary Publication(s) or References
Van Gelder IC. Hagens VE. Bosker HA. Kingma JH. Kamp O. Kingma T. Said SA. Darmanata JI. Timmermans AJ. Tijssen JG. Crijns HJ. Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. New England Journal of Medicine. 347(23):1834-40, 2002 Dec 5

Purpose of the Trial
The purpose of this study was to compare the long term effects of rate control versus rhythm control using electrical cardioversion in patients with persistent atrial fibrillation.

Study Catagory
Atrial Fibrillation. Randomized, multicenter, prospective trial

Patient Population
The patients were enrolled at 31 centers in the Netherlands.

Inclusion Criteria
Recurrent, persistent atrial fibrillation or flutter defined as non-self terminating arrhythmia requiring cardioversion, with no contraindication to anticoagulation. Patients had to have undergone between one and two cardioversions within the 2 years prior to enrollment.

Exclusion Criteria
Duration of arrhythmia greater than 1 year, NYHA functional class IV CHF, current or previous treatment with amiodarone or pacemaker.

Study Design
Patients were randomly assigned to either a rate control or rhythm control strategy. Rate control was achieved with beta-blockers, calcium channel blockers, and digitalis, either alone or in combination. The target for rate control was a resting heart rate of less than 100 bpm. Cardioversion or AV node ablation with implantation of a pacemaker was allowed if symptoms of AF were intolerable; if intolerance to the rate control medications occurred, or if LV dysfunction occurred as a result of AF (tachymyopathy).

The rhythm control group underwent initial cardioversion without any anti-arrhythmic drugs. After the first cardioversion patients were placed on sotalol. If AF recurred within six months, cardioversion was repeated and sotalol replaced by flecanide or propafenone. If AF recurred within six months of the second cardioversion, amiodarone was started and another cardioversion attempted. If AF recurred after six months of the initiation of any antiarrhythmic regimen, that drug was continued.

Anticoagulation with either acenomoumarol or fenprocoumon (target INR 2.5-3.5) was mandated for four weeks prior and four weeks after cardioversion. If four weeks after cardioversion, sinus rhythm was present, oral anticoagulation could be stopped or replaced with low dose aspirin. Patients in the rate control group were allowed to be on aspirin in the absence of structural heart disease if they were younger than 65 years. All other patients received anticoagulation therapy.

Primary Endpoints

The combined primary endpoint was death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, need for a pacemaker, or severe adverse effects of an antiarrhythmic drug.

Secondary Endpoint
None

Baseline Characteristics

	Rate Control (n=256)	Rhythm Control (n=266)
Mean Age (yrs)	68	68
Male Sex (%)	63	64
Median duration of current AF episode (days)	32 (1-399)	34 (1-395)
CAD (%)	29	26
Valvular Disease (%)	18	16
HTN (%)*	43	55
CHF history (%)	51	49
Mean LA size (mm)	45	45
Mean Fractional Shortening (%)	30	30

*There were significantly more patients with hypertension in the rhythm control group (p=0.007)

Time to Follow-up: 

The mean follow up time was 2.3 years.

Results
The primary endpoint was reached in 17.2% of the rhythm control group and 22.6% of the rate control group. This 5.4% absolute difference in the primary endpoint translated into a trend favoring the rate control group with the 90% confidence interval of -11.0 to 0.4%. This met the preset non-inferiority criteria and approached superiority of the rate control group over the rhythm control group. When reanalyzed to adjust for the baseline difference in hypertension between the two groups, this non-inferiority persisted. There were no significant differences in the separate components of the primary combined endpoint between the two groups except for the rate of severe adverse effects of antiarrhythmic drugs which occurred more frequently in the rhythm control group (4.5% vs. 0.8% (90% C.I. -6.0 to -1.4)

39% of the rhythm control group was in sinus rhythm at last follow up, while 10% of the rate control group was in sinus rhythm. In subgroup analysis, the primary endpoint occurred significantly more frequently in the rhythm control group among women and patients with hypertension.

Sponsor
Center for Health Care Insurance
Interuniversity Cardiology Institute, the Netherlands
Unrestricted Grant 3M Pharma, the Netherlands

Trial Status: Completed