lenient versus strict rate control ?
DESCRIPTION
Critical AppraisalLenient versus Strict Rate Control in Patients with Atrial Fibrillation(NEJM April 15, 2010 )TRANSCRIPT
Lenient versus Strict Rate Control in Patients with Atrial Fibrillation
(NEJM April 15, 2010 )
Piti Niyomsirivanich ,MD.
• Atrial Fibrillation is NOT a benign condition– Stroke– Heart failure
Treatment
• Rate Control• Rhythm Control
RACE trialRAte Control versus Electrical cardioversion for persistent atrial fibrillation study group
A Comparison of Rate Control and Rhythm Control in Patients with Recurrent Persistent Atrial FibrillationNEJM Volume 347:1834-1840 December 5, 2002
AFFIRM TrialAtrial Fibrillation Follow-up Investigation of Rhythm Management
Cumulative Mortality from Any Cause in the Rhythm-Control Group and the Rate-Control Group.
A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation
NEJM Volume 347:1825-1833 December 5, 2002
Rate Control has become front-line therapy
• BUT….
– The level of heart rate control is remain UNKNOWN
Strict rate control VS Lenient ???
Criteria for rate control vary with patient age but usually involve achieving ventricular rates between 60 and 80 beats per minute at rest and between 90 and 115 beats per minute during moderate exercise.
Rate Control• Guidelines (No Evidence-based)
– Suggest…Strict rate control – 60 and 80 beats per minute at rest– between 90 and 115 beats per minute during moderate
exercise.• Reduce symptom• Improve QOL & Exercise tolerance• Reduce heart failure• Improve survival
– Harm ??• Drug-relate adverse effect
– Bradycardia , Need for pacemaker implantation
To determine
• Hypothesis
Whether Lenient rate control is not inferior to strict rate control.
RACE II
• The RAte Control Efficacy in Permanent Atrial Fibrillation: a Comparison between Lenient versus Strict Rate Control II
• A Prospective, multicenter, randomized, open-label, noninferiority trial
Participation
• Interuniversity Cardiology Institute of the Netherlands• University Medical Center Groningen• Working Group on Cardiovascular Research of the
Netherlands
• Founded by Natherlands Heart Foundation– Unrestricted educational grants from pharmaceutical and
device companies
– None were involved in the study design, data collection, data analysis manuscript preparation
Methods33 Centers in the Netherlands
Jan 2005 - June 2007
Eligibility criteriaAF up to 12 months
Age <80Resting rate > 80
Current use of anticoagulant therapy or aspirin
Randomization And Treatment
• Informed consent
• Randomization– accomplished by means of a central telephone
system with use of permuted blocks of various size
• Dose Adjustment phase– Pts. Were administered [alone or combination]
• Beta-blocker , non-dihydropyridine CCB , digoxin • Until the heart –rate target were achieved
Randomization And Treatment
Lenient ControlVentricular rate <110 bpm
(Resting)
Strict ControlVentricular rate <80 bpm
(Resting)
(Determine by ECG after 2-3 min of rest in supine position)
• Follow-up outpatient visits occurred every 2 wks until the ventricular rate targets were archived
• During follow-up period– Resting ventricular rate was assessed by attending
physician at each visit– If heart rate target could not be achieved
• The study protocol permitted further adjustment of rate control drugs.
Randomization And Treatment
Primary outcomeme
•Death from cardiovascular causes•Hospitalization for heart failure•Stroke •Systemic embolism•Major bleeding•Arrhythmic events (syncope,VT,cardiac arrest)•Implantation of Pacemaker/Cardioverter
Death from any causeSymptoms
Functional Status
secondary outcome
Statistical analysis
Non inferiority trial
Study size was determined by expected rate of primary outcome 25% at 2.5 yrs(based on the observed events rate in the rate control group of RACE trial)
A sample size of 250 patients with a median follow up of 2.5 years satisfied the statistical requirements
Statistical analysis
• Primary analysis : Kaplan-Meier curves
614 patients enrolled33 Centers in the Netherlands
Jan 2005 - June 2007
Lenient control311
Strict control303
Randomization
Randomization and Follow-up of the Study Patients.
Heart rates
• Resting Ventricular Rate– lenient control group 93+-9 beats per min– Strict control group 76+-12 beats per min
Nine patients of both group were in sinus rhythm at the end of follow up
Rate Control Targets and Drug Therapy at the End of the Dose-Adjustment Phase
Primary outcome
Hazard ratio 0.84
95%CI 0.58 to 1.21
Lenient Control is NONINFERIOR to Strict Control
Secondary Outcome
Lenient Control Strict ControlDeath from any cause
17 (5.6%) 18 (6.6%)
Death from CVS 8 7Symptom associate with AFDyspnea 30% 29.6%Fatigue 24.4% 22.6%palpitation 10.6% 9.5%
Secondary OutcomeNYHA classification
Lenient Control Strict ControlClass I 70.0% 70.4%
Class II 23.3% 23.4%Class III 6.7% 6.2%
Class IV 0 % 0 %
Subgroup Analysis (CHADS2 score =2 or more)
Lenient Control Strict ControlPrimary outcome 17/133 25/108
Subgroup Analysis (CHADS2 score <2)
Lenient Control Strict ControlPrimary outcome 21/178 18/195
Criticized Paper
Is the study VALID ?
• Was the assignment of patients to treatment randomized?– Yes , the assignment of patients was randomized.
• Was the randomization concealed– The randomization accomplished by means of a
central telephone system with use of permuted blocks of various size.
Is the study VALID ?
• Were the groups similar at the start of the trial ?– The groups were similar except
• In the lenient rate control group has more patients with cardiovascular disease than strict rate control (67 vs 44)
– AND
• In the lenient rate control group has more usage of statin than strict rate control 103 vs 74
Is the study VALID ?
• Was the follow up complete?– Yes ,Study size was determined by expected rate of
primary outcome 25% at 2.5 yrs(based on the observed events rate in the rate control group of RACE trial)
Is the study VALID ?
• Were patients, their clinicians, and study personel “blind” to treatment ?– The patients were not blind to treatment
medication.– Their clinicians were not blinded.
• Were they analysed in the groups to which they were randomised- Intention to treat analysis
Is the study VALID ?
• Aside from the experimental treatment, were the groups treated equally?
– The other medications of both group were slightly different.
• Patients in lenient control group receive ARB/ACEI (166 VS 140) and Statins (103 VS 74) more than patient in strict control group slightly.
What were the results• How large was treatment effect?
– Primary outcome• Death from cardiovascular cause• Hospitalization due to heart failure• Stroke• Systemic embolism• Major bleeding• Arrhythmic Events• Life threatening adverse effects of rate control drugs• Implantation of a pacemaker or cardioverter-defibrillator
– Hazard ratio of Lenient control compare with Strict control is 0.84 (95% CI 0.58 to 1.21)
Can the results be applied to our patient care ?
• Is our patient so different from those in the study ?– Not so different , the pathophysiology are similar.
• Is the treatment feasible in our setting ?– Yes , the treatment is feasible in our setting.
Thank you