Amiodarone Prophylaxis for Atrial Fibrillation After Heart Surgery
Amiodarone Prophylaxis for Atrial Fibrillation After Heart Surgery
ABSTRACT & COMMENTARY
Synopsis: Preoperative oral amiodarone prior to cardiac surgery is well tolerated, reduces the incidence of postoperative atrial fibrillation, and decreases the duration and cost of hospitalization.
Source: Daoud EG, et al. N Engl J Med1997;337: 1785-1791.
Atrial fibrillation is a frequent complication of cardiac surgery that often increases hospital length-of-stay. Thus, Daoud and associates studied the effects of one week of oral amiodarone on postoperative atrial fibrillation in patients undergoing elective cardiac surgery. Patients scheduled for elective surgical procedures at the authors’ institution were screened for eligibility. Important exclusion criteria included chronic atrial fibrillation, current use or past intolerance to amiodarone, significant bradycardia, and current use of other antiarrhythmic medications. A total of 124 eligible patients consented to participate, were randomized, and actually began drug therapy. Sixty-four patients were randomized to receive amiodarone—200 mg three times daily for seven days, then 200 mg daily until hospital discharge. Digoxin and warfarin dosages were decreased in all patients. Therapy was initiated 13 ± 7 days prior to surgery. Fifty-two patients underwent coronary artery bypass graft surgery, 41 patients underwent valvular surgery, 22 patients had both coronary revascularization and valve surgery, and nine patients had non-coronary non-valvular cardiac surgery. Patients were monitored continuously after operation, either in an intensive care unit or on a monitored ward. Hospital discharge took place 7.2 ± 3.6 days after surgery. The primary end point of the study was an episode of atrial fibrillation of at least five minutes duration. Cost data for the initial hospital admission were compared between the two groups.Sixty-four patients were randomized to receive amiodarone, and 60 were randomized to receive placebo. One patient in each group did not complete the preoperative portion of the study due to minor gastrointestinal side effects. No other significant side effects of outpatient therapy were noted. Analysis of intraoperative and early postoperative surgical data did not reveal significant differences between the groups. Amiodarone significantly reduced the prevalence of atrial fibrillation in the first 21 days after surgery. Sixteen of 64 patients (25%) in the amiodarone group developed atrial fibrillation in contrast to 32 of 60 (53%) patients in the placebo group. If only atrial fibrillation episodes of more than eight hours duration are counted, 11 of 64 (17%) amiodarone patients and 16 of 60 (27%) control patients had such episodes. One episode of atrial fibrillation in the amiodarone group and seven episodes in the control group occurred after the initial hospital discharge. Only two episodes of atrial fibrillation required electrical cardioversion—both in the control group. All other episodes either terminated spontaneously or after addition of an antiarrhythmic medication. In those patients who developed atrial fibrillation, the maximum documented ventricular rate was significantly lower in the amiodarone group (111 ± 21 vs 135 ± 31 beats per min). In this study, beta blocker use did not influence the prevalence of atrial fibrillation. Valvular surgery was associated with a higher atrial fibrillation prevalence. Atrial fibrillation occurred in 46% of the valvular surgery patients, compared to 29% of the coronary revascularization patients.
Significant postoperative complications occurred in eight control patients and 11 amiodarone patients (P = NS). There were five deaths in the amiodarone group and three in the placebo group. Hospital stay was shorter in those who received amiodarone (6.5 ± 2.6 vs 7.9 ± 4.3; P = 0.04). The development of atrial fibrillation was associated with a prolonged hospital stay in both groups. The mean cost for hospitalization was $18,375 ± 13,863 in the amiodarone group, compared to $26,000 ± 49.1 ± 23,837 for the placebo group.
Daoud et al conclude that preoperative oral amiodarone prior to cardiac surgery is well-tolerated, reduces the incidence of postoperative atrial fibrillation, and decreases the duration and cost of hospitalization.
COMMENT BY JOHN P. DiMARCO, MD, PhD
Atrial fibrillation is a common problem after cardiac surgery. In patients undergoing coronary revascularization, 15-30% of patients will develop atrial fibrillation. Atrial fibrillation typically occurs between two and eight days after operation. In the absence of other factors predisposing the patients to atrial fibrillation, it usually resolves within three to four weeks after surgery. Although usually not life-threatening, postoperative atrial fibrillation delays hospital discharge and is a common cause of unplanned readmission in patients who are discharged early after operation. Beta adrenergic blockers are now the best accepted prophylactic therapy to prevent postoperative atrial fibrillation. In this paper, Daoud et al present data showing that preoperative amiodarone may offer benefits over and above beta blocker therapy.Amiodarone is currently FDA approved only for therapy of ventricular arrhythmias, but the drug is commonly used to prevent recurrent atrial fibrillation. Amiodarone has limited potential for early proarrhythmia, except in patients at high risk for bradycardia or with prior sustained VT. In patients after myocardial infarction and in patients with congestive heart failure, outpatient initiation of amiodarone therapy has proven to be safe. Although chronic therapy may be associated with numerous forms of organ toxicity, these adverse reactions develop with chronic exposure, and short-term, moderate dose therapy is usually well-tolerated. These properties make amiodarone an attractive candidate for short-term prophylactic therapy in a setting where risk of arrhythmia tends to be self-limited.
The study by Daoud et al included a high proportion of patients with mitral valve disease, a population likely to be at the highest risk for episodes of atrial fibrillation that would be expected to be particularly difficult to manage. This may explain the dramatic decrease in costs with effective prophylaxis in this study. The data presented suggest that the magnitude of benefit would be much smaller in patients with only coronary artery disease. However, the slowly progressive nature of valvular heart disease makes it more feasible to arrange an elective prehospital course of therapy in these patients.
This was a relatively small study, and its power to detect differences in serious morbidity and mortality was extremely limited. A much larger number of patients will have to be studied to be certain that the insignificant increases in fatal and nonfatal complications in the amiodarone group were not due to the drug.
Atrial fibrillation post heart surgery is least likely if:
a. pericarditis develops.
b. the patient has COPD.
c. the patient is put on digoxin pre-op.
d. the patient is put on amiodarone pre-op.
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