RACE II RAte Control Efficacy in Permanent Atrial Fibrillation A Randomized Comparison of Lenient Rate Control versus Strict Rate Control Concerning Morbidity and Mortality Isabelle C Van Gelder, Hessel F Groenveld, Harry J Crijns, Jan G Tijssen, Hans H Hillege, Ype Tuininga, Marco Alings, Hans Bosker, Jan Cornel, Raymond Tukkie, Otto Kamp, Dirk J Van Veldhuisen, Maarten P Van den Berg, on behalf of the RACE II Investigators
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RACE II RAte Control Efficacy in Permanent Atrial Fibrillation A Randomized Comparison of Lenient Rate Control versus Strict Rate Control Concerning Morbidity.
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RACE II
RAte Control Efficacy in Permanent Atrial Fibrillation
A Randomized Comparison of Lenient Rate Control versus Strict Rate Control Concerning Morbidity and
Mortality
Isabelle C Van Gelder, Hessel F Groenveld, Harry J Crijns, Jan G Tijssen,Hans H Hillege, Ype Tuininga, Marco Alings, Hans Bosker, Jan Cornel,
Raymond Tukkie, Otto Kamp, Dirk J Van Veldhuisen, Maarten P Van den Berg,on behalf of the RACE II Investigators
Rates of complications and death were similar in patients treated with rate-control and rhythm-control therapy
Since then, rate control has become front-line therapy in the management of AF
The optimal level of heart-rate control during AF is unknown
AFFIRM, RACE
Wyse et al. New Engl J Med 2002Van Gelder et al. New Engl J Med 2002
ACC/AHA/ESC 2006 Guidelines
Strict rate control
At rest: 60 - 80
During moderate exercise: 90-115
Fuster et al. Guidelines J Am Coll Cardiol 2006
Strict rate control ?
Contra
Difficult to achieve
Adverse effects drugs
More frequent pacemaker implants
Higher costs
Hypothesis
Lenient rate control is not inferior to
strict rate control in patients with
permanent AF in terms of
cardiovascular morbidity and mortality
RACE II trial
Prospective, randomized, open trial with
blinded endpoint evaluation
Multicenter, noninferiority trial conducted in
The Netherlands
2-3 years follow-up
Inclusion criteria
Permanent AF ≤ 12 months
Resting heart rate > 80 bpm
On oral anticoagulation
Age ≤ 80 years
Exclusion criteria
Paroxysmal or transient AF Known contra-indications for either strict or
lenient rate control (e.g. previous adverse effects on rate control drugs)
Unstable heart failure Cardiac surgery < 3 months Stroke Current or foreseen PM/ ICD/ CRT Inability to walk or bike
The null hypothesis of inferiority will be rejected when the upper limit of the 2-sided 90%-confidence interval of the risk difference does not exceed 10%.
Statistical analysis
* Comparable to the noninferiority boundary in the first RACE trial
Inferiority hypothesis rejected for both subgroups (*p=0.02 and **p<0.001)
Primary outcome
Symptoms
0
20
40
60
80
100
120
palpitations
fatigue
dyspnea
Lenient Strict Lenient Strict
% S
ymp
tom
s
PalpitationsFatigueDyspnea
baseline
end of study
The RACE II study shows that lenient rate control is not inferior to strict rate control
Lenient rate control is more convenient since fewer outpatient visits, fewer examinations, lower doses and less often combination of drugs are needed
Conclusions
Lenient rate control may be adopted as first choice rate control strategy in patients with permanent atrial fibrillation
This applies for high and low risk patients
Clinical implications
Van Gelder,Groenveld,Van Veldhuisen, Van den Berg University Medical Center Groningen
Janssen, Tukkie Kennemer Hospital HaarlemBendermacher, Olthof Elkerliek Hospital HelmondRobles de Medina Hospital Leyenburg The HagueKuijer, Zwart Hospital Bernhoven OssCrijns Maastricht University Medical CenterAlings Amphia Hospital BredaPost Hospital HengeloPeters, Van Stralen, Buys Hospital Gooi Noord BlaricumDaniëls Jeroen Bosch Hospital Den BoschTimmermans Medical Spectrum Twente EnschedeKuijper, Van Doorn Spaarne Hospital HoofddorpHoogslag Diaconessen Hospital MeppelDen Hartog Hospital Gelderse Vallei EdeVan Rugge Diaconessen Hospital LeidenDerksen, Bosker Rijnstate Hospital ArnhemHamraoui Tweesteden Hospital TilburgDe Milliano Hospital HilversumKamp VU Medical Center AmsterdamKragten Atrium Medical Center HeerlenLinssen Twenteborg Hospital AlmeloTuininga, Badings Deventer Hospital DeventerNierop St. Franciscus Hospital RotterdamGratama VieCurie Hospital VenloNio, Muys, Van den Berg IJsselland Hospital, Capelle aan de
IJsselThijssen Maxima Medical Center VeldhovenVan Dijkman Bronovo Hospital The HagueCornel Medical Center AlkmaarVan der Galiën St.Lucas Hospital WinschotenBoersma St.Antonius ospital NieuwegeinBronzwaer Zaans Medical Center De Heel
ZaandamSpanjaard Delfzicht Hospital DelfzijlBartels Martini Hospital Groningen
Steering CommitteeIsabelle C Van GelderHarry JGM CrijnsJan GP TijssenHans L HillegeYpe S TuiningaA Marco AlingsHans A BoskerJan H CornelOtto KampDirk J Van VeldhuisenMaarten P Van den Berg
Thesis ofHessel F Groenveld
Data Safety and Monitoring BoardHein J WellensRichard N HauerArthur A Wilde
Adjudication CommitteeJan Van der Meer†
Gert J LuijckxJohan Brügemann
Trial Coordination CenterHans L HillegeJanneke A BergsmaMarco AssmannOlga Eriks-De VriesMyke Mol
This article is now available on the
New England Journal of Medicine’s
website, NEJM.org
0 5 10 15 minutes 25% exercise duration
total exercise recovery
150
100
bpm
Heart rate moderate exercise
50
02 8
0 5 10 15 minutes 25% exercise duration
total exercise recovery
150
100
bpm
Heart rate moderate exercise
50
0
Heart rate 95 bpm
2 8
Symptoms
Lenient control Strict control
At baseline 56% 58%Palpitations 20% 27%Dyspnea 34% 37%Fatigue 28% 32%
At end of study 46% 46%Palpitations 11% 10%Dyspnea 30% 30%Fatigue 24% 23%
Patients were seen
Every 2 weeks until the rate control target
was achieved
After 1, 2 and 3 years of follow-up
Follow up visits
Primary outcome according to HRat end dose adjustment phase
Lenient control Strict
control
% (events/total pts)
Total group 12.9 (38/311) 14.9 (43/303)
Heart rate < 70 - (1/1) 20.4
(13/67)
Heart rate 70-80 20.0 (1/5) 11.7
(18/161)
Heart rate 81-90 15.0 (16/112) 10.7 (4/39)
Heart rate 91-100 9.1 (11/123) 5.6 (1/20)
Heart rate > 100 14.1(9/70) 46.4 (7/16)
Lenient control Strict
control
% (events/total pts)
Total group 12.9 (38/311) 14.9 (43/303)
Heart rate < 70 - (1/1) 20.4
(13/67)
Heart rate 70-80 20.0 (1/5) 11.7
(18/161)
Heart rate 81-90 15.0 (16/112) 10.7 (4/39)
Heart rate 91-100 9.1 (11/123) 5.6 (1/20)
Heart rate > 100 14.1(9/70) 46.4 (7/16)
Heart rate d at end ofdose adjustment phase
total exercise recovery
25% exercise duration
Strict rate control ?
Pro lower incidence CHF fewer strokes fewer bleeding better survival fewer symptoms improved quality of life
Contra difficult to achieve adverse effects drugs pacemaker implants higher costs