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Context
Atrial fibrillation (AF) represents a large and growing burden on cardiovascular healthcare and leads to a substantial impact on quality-of-life, increased cardiovascular events and a doubling of hospitalisation and death rates.1 Unlike many other cardiac conditions, the evidence base for treatment in AF remains patchy with clear gaps relating to a number of clinically important management strategies. Current practice involves three major elements: anticoagulation to prevent stroke or systemic embolism, medications to control heart rate and a decision on whether to restore and maintain sinus rhythm. This systematic review and meta-analysis of tabular data addresses the benefits and risks of adding rhythm control to rate control therapy, considers the preferential method of rhythm control and summarises the evidence for regulation of heart rate.
Methods
The study is based on a review commissioned by the US Agency for Healthcare Research and Quality, published online in June 2013. The authors primarily considered randomised controlled trials, restricted to papers published between 2000 and 2013, and a wide range of outcomes (with no specified primary outcome). There were limited numbers of trials included, for example, n=8 for all-cause mortality and incident stroke. Pooled results are presented following random-effects meta-analysis of the OR, rather than risk ratios which are clinically more intuitive and also more appropriate where outcomes are common.2 Overall strength-of-evidence ratings are provided, although the potential biases within each study are not discussed. The review was not prospectively registered with PROSPERO; however, study selection, data extraction and data synthesis are clearly stated.
Findings
For all-cause mortality, cardiac mortality and stroke, the authors report comparable effects for patients randomised to rate control alone or those receiving additional rhythm control therapy (OR all-cause mortality=1.34 (95% CI 0.89 to 2.02), OR cardiac mortality=0.96 (95% CI 0.77 to 1.20), OR stroke=0.99 (95% CI 0.76 to 1.30)). Barring two large trials, the included studies were small with resultant wide CIs. In addition, 5 of 10 trials included patients with persistent AF, 4 with paroxysmal or persistent AF and 1 with paroxysmal AF. For the maintenance of sinus rhythm outcome, a significant advantage was identified for pulmonary vein isolation, compared with antiarrhythmic drug (AAD) therapy (OR=5.87 (95% CI 3.18 to 10.85)), which included both paroxysmal and persistent AF patients. The lack of comparative studies for rate control medication was confirmed, with insufficient evidence to guide the choice of therapy.
Commentary
This carefully executed review replicates the findings of several previous meta-analyses concerning rate and rhythm control in AF, but leaves the clinical question of the value of rhythm control therapy unanswered. Two other studies have identified no significant difference for all-cause mortality comparing the two treatment strategies (OR=0.87 (95% CI 0.74 to 1.02) and OR=1.15 (95% CI 0.88 to 1.50)).3 ,4 Another study previously confirmed that catheter ablation maintains sinus rhythm better than AAD alone.5
The clinical application of these findings is troublesome, particularly as this review combines tabular data from different types of AF, which diverge in terms of mechanism, prognosis and the response to treatment. Another important limitation arises from enrolment of patients with prior treatment failures (eg, in the early AF ablation trials). Further, the major outcomes predominantly compare rate control (using a variety of combination therapies) with AAD and cardioversion. This does not necessarily reflect current clinical practice, which often includes hybrid therapy incorporating ablation and AAD.6 There has also been concern about the interpretation of intention-to-treat trials, particularly where cross-over rates are high. This review does highlight the important disparity in trial evidence for clinically important areas of management, including comparisons of rate control medication and outcome studies for ablation procedures. With the predicted prevalence of AF expected to double, we are in urgent need of adequately powered studies that guide the selection of specific rate and rhythm control therapies.7
Footnotes
Competing interests DK is the Steering Committee Lead for the β-blockers in Heart Failure Collaborative Group: Individual Patient Data Meta-Analysis.8 PK is a Board member of AFNET, an academic research organisation running trials in atrial fibrillation, and a recipient of research grants from the British Heart Foundation, DFG, Fondation Leducq, the European Union and others. He is also the principal investigator of the investigator-initiated EAST trial.6 A full list of financial disclosures is available on the website of the ESC.
Provenance and peer review Commissioned; internally peer reviewed.