These include azimilide (Stedicor, Procter & Gamble), dronaderone (Sanofi-Synthelabo), piboserod (GlaxoSmithKline), and others not yet as far along in their development.As (and if) they become available, the details of their clinical trials and the clinical trial databases should allow them to fit effectively into the recommended algorithms.

More problematic has been the issue of whether to pursue sinus rhythm goals in AF patients whose QOL is acceptable after attainment of ventricular rate control and who are appropriately anticoagulated.Will NSR in itself extend their life expectancy? Teleologically, we might believe that NSR, the native rhythm of our birth, should be better for us than AF; but in AF patients, NSR usually comes only with the application of some therapy (drug or procedure) whose risks may or may not offset any potential benefit of sinus rhythm itself.To examine this issue, five trials have been conducted (seeTables 1 and 2).(10–17) Three were small pilot studies and two were larger trials. They included studies known as Strategies of Treatment of Atrial Fibrillation (STAF), Pharmacological Intervention in Atrial Fibrillation (PIAF),HOT CAFÉ (a Polish study published so far only in abstract form without definition of the acronym), Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE), and Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM). Each of these has been presented at a major scientific meeting; STAF and HOT CAFÉ have been published in abstract form; PIAF, RACE, and AFFIRM(18,19) have been published as full manuscripts.(10–17)

Table 1: Recent Clinical Trials for AF Comparing Rate Control Versus Rhythm Control Strategies

Table 2: Adverse Outcomes of Recent AF Trials

KEY FOR TABLE 1 AND TABLE 2
AF: atrial fibrillation
AFFIRM: Atrial Fibrillation Follow-up Investigation of Rhythm Management
PIAF: Pharmacological Intervention in Atrial Fibrillation
RACE: Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation
STAF: Strategies of Treatment of Atrial Fibrillation

STAF compared outcomes in two randomly assigned groups of 100 patients, one group assigned to a strategy of rate control and one assigned to a strategy of rhythm control (cardioverted and then maintained on an AAD). There was no difference in the primary end point events (composite of total mortality, stroke, emboli, and cardiopulmonary resuscitation) or in secondary endpoints (LA and LV size by echocardiography, syncope, hospital admissions, QOL scores, and heart failure) except for more hospitalizations in the rhythm control arm. Of note, however, only 23% of the patients assigned to the rhythm control arm maintained sinus rhythm at three years (despite up to four AAD trials), and most events in this arm of the trial occurred while the patients were in AF.

PIAF compared outcome in 252 patients randomized to a rate control strategy (with diltiazem being the first agent tried) versus rhythm control (using amiodarone as the first agent tried) with a followup of one year.There was no difference in adequate symptom reduction, QOL scores, or mortality between the two arms, whereas amiodarone provided a longer six-minutewalk test but also led to more hospitalizations and a higher rate of adverse effects requiring discontinuation of therapy.

HOT CAFÉ compared outcome in 205 patients randomized to a rate-control strategy versus a rhythm control strategy (cardioverted, then sequentially tried on disopyramide, propafenone, sotalol, and amiodarone as needed). After one year, 75% of the patients in the rhythm control arm were in sinus rhythm.However, the rhythm control arm had more hospitalizations and more strokes, while New York Heart Association (NYHA) heart failure class improved in both groups. There was no difference in mortality.