Atrial fibrillation
Rate vs rhythm control
Dr. Yong Eu Ming
Introduction
• Atrial fibrillation (AF) is the most
common sustained arrhythmia in
adults, with approximately 44
million individuals estimated to
have AF or atrial flutter
worldwide.
• AF associated with substantial
mortality and morbidity, which
poses a significant burden to
patients and health care services
Current AF management
• Management comprises 3 main domains summarized in the ”ABC”
scheme of the 2020 ESC AF guideline
• A anticoagulation/avoid stroke
• B better symptoms control using rate and rhythm management
• C therapy of concomitant cardiovascular conditions
• Favoring rate control with rhythm control added specifically and
primarily to symptomatic patients
- (top) Current guidelines, largely recommending initial
rate control, with rhythm control added specifically and
primarily to symptomatic patients
- (right) rhythm control are also reserved for use only in
specific patient subgroup who might be expected to
benefit from rhythm-control strategy
• Guidelines of the recent ESC
2020, data derived from
AFFIRM, RACE, AF-CHF, STAF
and J-RHYTHM
• Overall, few significant
differences in important
endpoints have been observed
between rhythm- and ratecontrol strategies
• Meta-analyses however shown
fewer hospitalizations were
required to deliver simple rate
control
But why ???
• Maintained of sinus rhythm has itself
been associated with reduction in death
and cardiovascular events
• AADs approximately double likelihood
of maintaining sinus rhythm compare
with rate control
Hospitalizations rates
• The current guidelines defaults to initial rate control, as meta-analyse
have shown that fewer hospitalizations were required to deliver
simple rate control.
• They found that in rhythm control arm group, there were more likely to be
readmitted for adverse drug effects of AAD and the need for other rhythmcontrol interventions (i.e., left atrial ablation and cardioversion
• When treatment adjustments for rhythm control were excluded,
hospitalization rates from the AFFIRM analyses were similar in both cohorts.
Quality of living (symptoms control)
• Difficult to assess with pitfall during trials, because there isn’t a
standardized AF-specific tools to assess; in addition to small sample
size, short-term follow up periods.
• Findings from trials comparing both rate vs rhythm, both arm reported
improve QOLs but with little difference between the two
• However, recent observational trial, such as CABANA, RECORD-AF and ESCEHRA EORP-AL reported potential QoL benefit of rhythm control.
• AF ablation improves QoL more, because of chronotropic incompetence and resulting
impairment of effort tolerance due to AAD therapy
But why ……
• But large landmark trials still reported no significant difference… possible
reasons in the recent paradigm shifts.
• Trials conducted in 1980s and 1990s, lack of safe and effective therapies
• Less stringent monitoring
• Inadequate and unbalanced therapies for concomitant medical conditions and
anticoagulant therapy
• Nowadays, with introduction of ACEI / mineralcorticoids receptor antagonist / SGLT-2i, these
are seen to improve maintain of sinus rhythm
• Better lifestyle adjustment such as weight loss, management of sleep apnea
• AADs doses (inappropriately high or suboptimal) potentially reducing efficacy or
inciting proarrhythmic.
• Previously used anti-arrthymic were associated with excess mortality likely attributed by
AADs pro-arrhythmic or negative inotropic effect
• Nowadays, newer drugs are used which are less pro-arrhythmic (dronedarone)
• Ablations techniques improving
•SO ……
Rate or rhythm
New evidence supporting rhythm control
• ATHEA
ATHENA study
• Both arms included standard therapy including
rate control
• Included patients who met >= 1 CHADS2 risk
factors, left ventricular EF <= 40%, or left atrial
enlargement
• Other AADs were not included in this study
• Exclusion criteria: HF with NYHA class IV,
unstable heart failure patients
• Findings:
• Dronedarone reduce the risk of primary
outcome of hospitalization due to
unexpected cardiovascular events or
death from any cause compared with
placebo
• There was a significant reduction in
secondary outcomes with dronedarone
compared with control, including
cardiovascular death (secondary outcome)
and stroke *post hoc analysis)
Clinical benefit of early Rhythm management
- EAST-AFNET 4 study
• Study of 2789 patients with AF diagnosed within 12 months before randomization who were at risk
of stroke
• Trial included patient with these sets of criteria:
• Age > 75 years old
• Prior transient ischemic stroke
• Met 2 of the following: CHADVAS2 >=1, CKD, LVH
• 2 arms:
• usual care (guideline primary rate control plus OACs with rhythm control added to control symptoms);
n = 1394 and
• guideline-recommended care plus early rhythm control treatment, consisting typically of AAD therapy or , to a lesser
degree ablation; n = 1395
Findings:
- Primary outcomes composite of death from
cardiovascular causes, stroke (ischemic or hemorrhagic)
or hospitalization with worsening heart failure or acute
coronary syndrome, which was reduce by 21% in patients
assigned to early rhythm control compare with usual care
(P = 0.005)
- Secondary outcomes in terms of number of stay in
hospital, there was no significant difference between
both arm
Conclusion:
- Early rhythm control therapy was associated with lower
risk of adverse cardiovascular outcomes than usual care
among patients with early atrial fibrillation and
cardiovascular condition.
AF ablation for rhythm control
• Rapid development in ablation, evolving from an experimental procedure
to an important treatment option in AF
• Complication rate has declined in recent years due to quality improvement
initiatives and advancement in technique and technologies
• Studies, such as CASTLE-AF, CABANA (ablation > pharmacological)
•
•
•
•
Lower AF recurrence (37% vs 58% at 1 year-follow up, 50% vs 69% at 3 year)
Reduce AF burden
improvement in left ventricular ejection function
Primary endpoint (death or hospitalization for worsening heart failure) were
significantly fewer in the ablation group than in the pharmacological therapy group
(P = 0.006)
What can we derive from recent studies
• Benefits of early rhythm control have been shown for both
pharmacological therapy and ablation, to be highly effective
especially when used in recent-onset AF
• Dronedarone has most extensively studies AAD in terms of rhythm
control and adverse cardiovascular outcomes; and has been found to
be effective and safe
• AADs vs ablation, ablation is more superior
• Shorter (< 1year diagnosis) with ablation initiated, have shown to lower risk of
AF recurrence.
•SO ……
Rate or rhythm
References
(1) Camm A, Naccarelli G, Mittal S, et al. The Increasing Role of Rhythm
Control in Patients With Atrial Fibrillation. J Am Coll Cardiol. 2022
May, 79 (19) 1932–
1948.https://doi.org/10.1016/j.jacc.2022.03.337
(2) Stefan H., Harry J., G.M.Crinjns, Martin VE, et al. Effect of
Dronedaroen on Cardiovascular events in atrial fibrilations. N Engl J
Med. 2009; 360:668-678.
https://www.nejm.org/doi/full/10.1056/nejmoa0803778