Download Rationale for the Atrial Fibrillation and Congestive Heart Failure (AF

Rationale for the Atrial Fibrillation and
Congestive Heart Failure (AF-CHF) trial
Denis Roy
From the Department of Medicine and Research Center, Montreal Heart Institute
Montreal, Quebec, Canada.
The incidence of atrial fibrillation (AF) in patients with congestive heart failure (CHF) ranges from 10% to 50%,
with the highest incidence in those with the most severe symptoms [1-3] . Excessive ventricular rate,
irregularity of ventricular response, and loss of atrial contraction associated with AF may result in adverse
hemodynamic consequences and influence prognosis in patients with CHF [4-15] . Restoration of sinus rhythm
has been associated with improvement in cardiac output, exercise capacity, and maximal oxygen
consumption [5-11] . However, the impact of AF on survival remains controversial. Prior studies of AF and CHF
were all nonrandomized comparisons and most were retrospective analyses [1, 2, 16-21] . Some studies
suggested that AF had no effect on survival, but in some recent large reports, AF has been shown to be an
independent risk factor for mortality or major morbidity.
The recently published AFFIRM trial which compared the relative benefits of rhythm and rate control in the
management of AF did not demonstrate any significant differences between the 2 groups in terms of overall
mortality, morbidity and symptoms [22] . However, the AFFIRM trial was not designed and did not have the
power to establish optimal management of AF in patients with CHF. This specific subset of patients, under
represented in AFFIRM, are often felt by clinicians to require the additional contribution to cardiac output
afforded by the atrial kick and despite the potential adverse effects related to antiarrhythmic therapy there
exists a certain bias favouring rhythm control. However, the question of rate versus rhythm strategy in patients
with heart failure has never been compared in an adequately powered randomized trial.
The primary objective of the AF and Congestive Heart Failure (AF-CHF) trial is to determine whether restoring
and maintaining sinus rhythm significantly reduces cardiovascular mortality compared with a rate control
strategy in patients with AF and CHF [23] . AF-CHF is a prospective multicenter trial (130 centers in Canada,
United States, South America, Europe and Israel), that will randomize 1450 patients with New York Heart
Association class II to IV CHF and left ventricular ejection fraction 35% (NYHA class I patients with prior
hospitalization for heart failure or ejection fraction 25% are also eligible) and a documented clinically
significant episode of AF within the past 6 months to one of two treatment strategies.
1. Rhythm control with the use of electrical cardioversion combined with antiarrhythmic drugs
(amiodarone or other class III agents), and additional nonpharmacological therapy in resistant
patients.
2. Rate control with the use of beta-blockers, digoxin or pacemaker and AV node ablation if
necessary. Cardiovascular mortality is the primary end point and the intention-to-treat approach
is the primary method of analysis.
We anticipate an 18.75% 2-year cardiovascular mortality in the rate control arm with a 25%
mortality reduction in the rhythm control.
As of June 2003, 760 patients have been enrolled, 81% male. The average age is 66 years with the
predominant cardiovascular disease is coronary artery disease in 47% and primary cardiomyopathy in 37% of
patients. The mean left ventricular ejection fraction measured prior to randomization is 27±6%. Seventy-eight
percent of patients are treated with beta-blockers and 86% are receiving ACE inhibitors. Currently, over 90%
of patients are maintained in the treatment strategy to which they were assigned at randomization. Enrolment
is expected to be completed in May 2004 with a minimum follow -up of 2 years.
The results of this trial should provide definite information concerning two widely applicable treatment
strategies of AF in a large cohort of patients with CHF. If the study hypothesis is borne out, the data will
support a compelling indication for agressive treatment of AF with prompt cardioversion and long-term
antiarrhythmic therapy. Given the frequent occurrence of CHF and AF and the high mortality and
hospitalization rates associated with them, we postulate that even a modest improvement could prevent
thousands of hospitalizations and deaths each year. It would also provide a strong incentive to search for new
and improved methods to maintain sinus rhythm. On the other hand, if the trial yields negative results, it will
indicate that adequate rate control is sufficient therapy and will eliminate the need for cardioversion and
hospitalization in otherwise stable patients.
References
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patients with heart failure and atrial fibrillation: observations from the Veterans Affairs Congestive Heart Failure Survival Trial of
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referred for heart transplantation because of severe heart failure. Am J Cardiol 1999;83:1544 -1547.
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Updating: 09/19/2003