A comparison of rate control and rhythm control in patients with atrial fibrillation. Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation. Maintenance of sinus rhythm after conversion to sinus rhythm. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug.
There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended.
                We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality.
                A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic.
                Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.
                Copyright 2002 Massachusetts Medical Society Azimilide dihydrochloride (azimilide) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias. In patients with atrial fibrillation, it has shown excellent efficacy in some previous trials and minimal efficacy in others.
                Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter, randomized, placebo-controlled clinical trial. Patients were admitted to a hospital and randomly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily. Patients who were in sinus rhythm spontaneously or had sinus rhythm restored by electric cardioversion on day 4 were discharged from the hospital. Recurrence of atrial fibrillation was documented by electrocardiogram. In the primary efficacy analysis, time to recurrence in the 2 treatment groups was compared with the log-rank test in the subgroup of patients with structural heart disease. Safety was assessed as deaths, adverse events, and serious adverse events.
                A total of 446 patients were randomized in the study; 314 were in the subgroup with structural heart disease. The median time to arrhythmia recurrence in both treatment groups with structural heart disease was 13 days, and the difference between treatments was not significant (P = .4596, n = 314). The relative risk for recurrence (placebo:azimilide) was 1.104 (95% CI 0.849-1.436). There was 1 death in the placebo group and 3 in the azimilide group.
                Azimilide did not demonstrate clinically important or statistically significant efficacy in reducing the risk for arrhythmia recurrence in patients with structural heart disease who were in atrial fibrillation and converted to sinus rhythm. This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.
                Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.
                We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.
                Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.
                The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients. This study evaluated the efficacy of antiarrhythmic drugs for the treatment of atrial fibrillation (AF).
                The most effective and safest antiarrhythmic drug for the treatment of AF is unknown.
                The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study compared two treatment strategies--rate control and rhythm control--in patients with AF and risk factors for stroke or death. This substudy, performed in patients randomized to rhythm control, compared different antiarrhythmic drugs by randomly assigning the first drug treatment to: 1) amiodarone, 2) sotalol, or 3) a class I drug. The primary end point was the proportion of patients alive, in sinus rhythm, with no additional cardioversions and still taking the assigned drug at one year. Comparisons were made between patients eligible for each of three drug pairs.
                At one year, in 222 patients randomized between amiodarone and class I agents, 62% were successfully treated with amiodarone, compared with 23% taking class I agents (p < 0.001). In 256 patients randomized between amiodarone and sotalol, 60% versus 38% were successfully treated, respectively (p = 0.002). In 183 patients randomized between sotalol and class I agents, 34% versus 23% were successfully treated, respectively (p = 0.488), although this portion of the substudy was stopped early when amiodarone was shown to be better than class I agents. Sinus rhythm was achieved in nearly 80% of patients at one-year follow-up with serial therapy. Adverse effects were common.
                Amiodarone was more effective at one year than either sotalol or class I agents for the strategy of maintenance of sinus rhythm without cardioversion.
Based on the two major randomised trials (HELAS 2006; WASH 2004), there is no convincing evidence that oral anticoagulant therapy modifies mortality or vascular events in patients with heart failure and sinus rhythm. Although oral anticoagulation is indicated in certain groups of patients with heart failure (for example atrial fibrillation), the data available does not support its routine use in heart failure patients who remain in sinus rhythm. A large randomised trial of warfarin in heart failure patients in sinus rhythm is currently in progress and data from this trial will be a useful addition to this topic.