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Statins Prevent Post-Operative Atrial Fibrillation
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.
Synopsis: Treatment with atorvastatin 40 mg/d, initiated 7 days before surgery, significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay.
Source: Randomized Trial of Atorvastatin for Reduction of Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery: Results of the ARMYDA-3 (Atorvastatin for Reduction of Myocardial Dysrhythmia After cardiac surgery) Study. Patti G, et.al. Circulation. 2006; 114:1455-1461.
Patti and colleagues from the campus bio-Medico University in Rome report the results of Atorvastatin for Reduction of Myocardial Dysrhythmia After Cardiac Surgery study (ARMYDA-3). The study was designed to test whether atorvastatin significantly reduced the incidence of atrial fibrillation after cardiac surgery. All patients undergoing cardiac surgery with cardiopulmonary bypass over a 30-month period at a single institution were evaluated. Patients with a history of atrial fibrillation, a need for emergency cardiac surgery, previous or current treatment with statins, renal or hepatic disease, or any inflammatory disease were excluded. The final study group consisted of 200 patients, 99 of whom were randomized to placebo and 101 to atorvastatin, 40 mg per day, beginning 7 days before the scheduled surgery. Patients undergoing all types of cardiac surgery were eligible.
Patients were monitored continuously in the intensive care unit and then in a telemetry unit for at least 6 days after the operation. C-reactive protein levels were assessed in all patients before surgery and every 24 hours postoperatively until discharge. After discharge, patients were scheduled for weekly visits in the outpatient clinic for the first month. The primary end point of the trial was the incidence of postoperative atrial fibrillation. Atrial fibrillation was defined as an electrocardiographically documented episode that lasted greater than 5 minutes or required earlier intervention. Total arrhythmia burden was quantified on the basis of a number of atrial fibrillation episodes per patient, the ventricular response, the postoperative response to recurrence, and the total duration of the episodes. Secondary end points included the length of postoperative stay and the incidence of major adverse cardiac and cardiovascular events. The authors correlated the pre- and post-operative peak C-reactive protein (CRP) levels with the occurrence of atrial fibrillation and attempted to identify variables that were predictors of outcome.
The 2 groups were well matched. The mean age was slightly older than 65 and approximately two-thirds of patients were male. Almost one-third of patients had chronic obstructive pulmonary disease and 25% were smokers. The mean left ventricular ejection fraction was slightly greater than 50%. Most had coronary revascularization only, but 25% had valve surgery with or without revascularization.
Postoperative atrial fibrillation occurred in 35 (35%) of 101 patients in the atorvastatin arm vs 56 of 99 (57%) patients in the placebo arm (P = 0.003). Among patients who developed atrial fibrillation, there was no difference in the mean ventricular response, time to occurrence, or the total duration of episodes. In patients who developed atrial fibrillation, intravenous infusion of amiodarone restored sinus rhythm in all patients. No patients had recurrence of the arrhythmia after termination of the first episode.
The mean postoperative stay was significantly lower in the atorvastatin group (6.3 ± 1.2 days) vs the placebo group (6.9 ± 1.4 days). Major adverse cardiac events, however, were similar. The baseline preoperative CRP levels did not differ between the groups and did not change after surgery. However, CRP levels were higher among those patients who developed atrial fibrillation regardless of randomization assignment. By multivariate analysis, age over 65, systemic hypertension, aortic atherosclerosis, and an elevated CRP were predictors of postoperative atrial fibrillation. Therapy with beta blockers, atorvastatin, and in particular, the combination of these two agents predicted freedom from atrial fibrillation.
The authors conclude that the ARMYDA-3 Trial demonstrates that treatment with atorvastatin reduces the incidence of new onset postoperative atrial fibrillation and produces a short but significant decrease in hospital stay. They urge that routine statin therapy be employed in these patients.
This is a relatively small study and there are some limitations in the trial design. However, it does illustrate that there is a developing paradigm shift in the management of arrhythmias. Formerly, most antiarrhythmic drug therapy concentrated on agents which blocked cardiac ion channels. Beta blockers, ACE inhibitors and statins have now been shown to have profound effects on arrhythmia frequency, and, in fact, may be more effective overall than traditional antiarrhythmic drugs.
There are some limitations to the data presented here. It is surprising that two-thirds of the patients screened were not previously treated with statins before undergoing bypass surgery. The incidence of postoperative atrial fibrillation in the control group is also quite high, much higher than in many other similar trials. Despite these limitations, however, the data are provocative and point out that strategies directed at the factors which predispose towards arrhythmias should always be considered first and traditional antiarrhythmic drugs used only as needed.