There was no difference in mortality when rate control versus rhythm control was used in the management of atrial fibrillation

 

Clinical Problem: A 66 year old man, who has had a prior stroke, has an episode of atrial fibrillation, recorded on EKG, lasting more than six hours.

 

Clinical Question: Does rhythm control decrease mortality relative  to rate control in the treatment of atrial fibrillation?

 

Search Strategy:

Keywords: (MeSH terms) “atrial fibrillation” AND “heart rate” AND “cardioversion”

Limits: RCT or Meta-analysis, Human, English, 5 years

Sources: PubMed, DARE, SumSearch, Cochrane

Results: 21 articles, three of which were relevant.RCTs:  The HOT CAFE trial (ref. 1) examined management of persistent atrial fibrillation (>7d); the RACE trial (ref. 2) examined management of recurrent persistent atrial fibrillation or flutter (>10d); the AFFIRM trial (ref. 3, 4) was selected for review as it was broader, allowing inclusion of patients with new-onset or episodic atrial fibrillation and examining management after as few as six hours of atrial fibrillation.  No relevant meta-analyses were found.  One set of guidelines from the ACC/AHA/ESC was found (ref. 5), but these guidelines were published before the three relevant RCTs and were therefore not considered up-to-date. 

 

Clinical Bottom Lines:

1.      A rhythm control strategy was neither superior nor inferior to a rate control strategy in preventing mortality in patients with atrial fibrillation. (RR=1.15; 95%CI from 0.99 to 1.34)

2.      Comparison of the incidence of pre-specified adverse events between rate- and rhythm-controlled groups showed either nonsignificant differences or a benefit with rate control.

3.      The risk of ischemic stroke in a patient with atrial fibrillation is 6.3% overall (at five years) with no significant difference between management strategies.

 

The Evidence: The AFFIRM study is an unblinded, randomized, multicenter treatment study involving 4060 patients, which compares a rhythm control strategy to a rate control strategy for the management of atrial fibrillation.  All patients were aged 65 or older, or had at least one risk factor for stroke.  The primary endpoint was mortality; a composite secondary endpoint comprised death, disabling stroke, disabling anoxic encephalopathy, major bleeding, and cardiac arrest. 

 

Data:

Number of patients enrolled: 4060

Study period: November 1995 – October 1999, at 213 centres

Average duration of follow-up: 3.5 years (range 2 years to 6 years)

 


                        Rate control                   Rhythm control                          Total

Number dead:          310                                 356                                     666

Number alive:         1717                               1677                                   3394

Total:                    2027                               2033                                   4060

 

RR = (356/2033) / (310/2027) = 1.15; 95%CI = 0.99 to 1.34; P = 0.08

ARR = N/A        RRR = N/A

 

Comments:

1.       Well-designed trial:  Randomized, ITT analysis, low dropout rate, subgroup analysis pre-specified

2.       Not a blinded trial.

3.       This trial compared strategies for management of atrial fibrillation, not specific drugs.

4.       Kaplan-Meier curves suggest a trend toward increased mortality with time in the rhythm-controlled arm, but the effect does not achieve significance.

5.       The authors stress that anticoagulation should be continued in all patients with atrial fibrillation.

6.       It is not clear where the authors enroll their patients from – clinics, emergency rooms, etc.

7.       The authors do not describe how many patients in each group have had prior strokes.

8.       The HOT CAFÉ and RACE trials show similar findings to the AFFIRM trial.

9.       The methodology and study design of the AFFIRM trial are described in much more detail in a previously published paper (see Reference 4, below).

 

References:

1.       Opolski G, Torbicki A, Kosior D, Szulc M, Zawadzka M, Pierscinska M, Kolodziej P, Stopinski M, Wozakowska-Kaplon B, Achremczyk P, Rabczenko D.  “Rhythm control versus rate control in patients with persistent atrial fibrillation.  Results of the HOT CAFE Polish Study.”  Kardiol Pol.  2003 Jul; 59(7):1-16.

2.       Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermans AJ, Tissen JG, Crijns HJ.  “A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation.” [RACE trial].  N Engl J Med.  2002 Dec 5; 347(23): 1834-40.

3.       Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD.  “A comparison of rate control and rhythm control in patients with atrial fibrillation.”  [AFFIRM trial].  N Engl J Med.  2002 Dec 5; 347(23): 1825-33.

4.       The Planning and Steering Committees of the AFFIRM Study for the NHLBI AFFIRM Investigators.  “Atrial fibrillation follow-up investigation of rhythm management – the AFFIRM study design.”  Am J Cardiol 1997; 79:1198-1202.

5.       http://www.acc.org/clinical/guidelines/atrial_fib/af_index.htm

 

Key Words: atrial fibrillation, arrhythmia, rate control, rhythm control, cardioversion

 

Appraiser: Alex Fraser and the UWO Evidence Based Neurology Group

 

Date Appraised: May 2004

 

                                                                                   

Copyright 2002-2004

Evidence Based Neurology Group

University of Western Ontario