Rate vs. rhythm control in patients with atrial fibrillation — An updated meta-analysis of 10 randomized controlled trials

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affectingmore than 2 million adults in theUnited States [1]. Rate control and rhythm control, both combined with anticoagulation therapy, are two fundamental strategies to treat AF. A series of randomized controlled trials (RCTs) were performed to compare the two strategies, but which one is better still has been the focus of controversy [2–11]. Therefore, we systematically performed an updated meta-analysis to compare rate and rhythmcontrol strategy in terms of all causemortality and worsening heart failure. We included studies if they met: 1) a study population with nonvalvular AF, 2) comparison of a ventricular rate control strategy and rhythm control strategy, 3) prospective randomized controlled trial, 4) intention-to-treat principle, 5) follow-up period N1 year. Electronic and literature search was performed in MEDLINE, The Cochrane Library, The Clinical Trials and Embase Database or the abstract of ACC (American College of Cardiology), AHA (AmericanHeart Association), and ESC (European Society of Cardiology) up to June 30, 2011 using the search term “atrial fibrillation, rate control, rhythm control, randomized trial”. Fig. 1 shows the study selection process. Finally, ten RCTs [2–11] were included in this meta-analysis. The baseline characteristics of included studies were presented in Table 1. The therapeutic approaches included atrioventricular node blockade: beta-blockers, digitalis or calcium blockers in the rate control group and antiarrhythmic agents, electrical cardioversion in the rhythm control group. The anticoagulation therapy was implemented according to the guideline. Amiodarone combined electrical cardioversion was the frequently used regimen in rhythm control group. Data for all cause mortality was reported in all included trials [2– 11]. There was no significant result in individual study regarding this outcome.When results from10 trialswere pooled, the impact of rate and rhythm control strategies still appeared to be equivalent on all cause mortality (5.3% vs. 5.0% per year; OR: 1.03; 95% CI: 0.84–1.26) with no significant heterogeneity (P=0.44, Ib25%). When we excluded 5 studies [2, 4, 5, 8, 9]withmeanageN65, rate control groupwas associated with a significant higher risk of all cause mortality when compared with rhythm control group (3.6% vs.1.9% per year; OR: 1.89; 95% CI: 1.01–3.53) with no significant heterogeneity (P=0.32, Ib25%) (Fig. 2). Data for worsening heart failure was reported in 6 studies [2–4, 7, 9, 10], thepooled result showed that the rate and rhythmcontrol grouphad a similar rate of worsening heart failure (3.81% vs. 3.61% per year; OR: 1.04; 95% CI: 0.80–1.36) with no significant heterogeneity (P=0.20; Ib50%). when we excluded studies with mean age N65 [2, 4, 9], the pooled result showed that rate control grouphad a significanthigher risk ofworsening heart failure events (2.3% vs. 0.3% per year; OR: 5.6; 95%CI: 1.44–21.69)with no significant heterogeneity (P=0.85, Ib25%) (Fig. 3). There was no significant difference on thromboembolic events (1.49% vs. 1.46% per year; OR: 1.02; 95% CI: 0.71–1.48) and bleeding events (1.78% vs. 1.73% per year; OR: 1.02; 95% CI: 0.70–1.49) between rate and rhythm control, even in the mean age b65 subgroup, (2.67% vs. 1.80% per year; OR: 1.49; 95% CI: 0.76 to 2.90) for thromboembolic events, (0.84% vs. 0.97% per year; OR: 0.86; 95% CI: 0.31–2.41) for bleeding events, respectively. Strategy to manage AF is expected by years not days. A survival analysis for the AFFIRM study showed that the maintenance of sinus was associated with a 47% reduction of overall mortality, whereas, the use of anti-arrhythmic drugs increased the risk of death by 49%. The survival benefit of rhythm control was greatly negated by the side effect of anti-arrhythmic drugs but not rate control strategy [12]. Age was correlative predictive factor inversely related to cardiac function and success rate of restoration of sinus rhythm. Younger AF patients were observed to have shorter AF duration, smaller atrial volume and higher success rate of reestablishment of sinus rhythm, which suggested these patients receiving rhythm control strategy tend to have higher success rate and more survival benefit. Heart failure usually complicated AF, and it helps increase the cardiovascular mortality. Annual incidence of worsening heart failure was 3.7% in this meta-analysis, with the highest rate (12.7%) occurred in study conducted by Roy et al.'s study [9], where death from heart failure occupied 30% of total mortality. The meta-analysis revealed that rhythm control strategy in younger AF patients was associated with a significantly lower risk of worsening heart failure compared with rate control strategy. It is worth mentioning that this positive result from rhythm control strategy was mostly based on pharmacological therapy and electrical cardioversion but not ablation yet. In summary, this meta-analysis suggests that rhythm control strategy may be preferable to younger AF patient for all cause mortality and worsening heart failure.