Prophylactic Amiodarone for Heart Surgery
ABSTRACT & COMMENTARY
Synopsis: Administration of oral amiodarone for seven days prior to elective cardiac surgery and continuing until the day of discharge significantly reduces the rate of post-operative atrial fibrillation from 53% to 25%.
Source: Daoud EG, et al. N Engl J Med 1997;337: 1785-1791.
In this randomized, double-blind study, 64 patients received 600 mg oral amiodarone for seven days prior to cardiac surgery (mean, total outpatient dose 4.8 g) and 200 mg per day following surgery until the time of discharge. Another 60 patients received placebo. Patients were excluded if they were less than 18 years of age, were in chronic atrial fibrillation, or used antiarrhythmic medications. Forty-two percent of the patients underwent coronary-artery bypass graft surgery (CABG), 33% underwent valvular surgery, and 18% had both surgeries. All patients entered in the study were placed on cardiopulmonary bypass, for a mean pump time of approximately 150 minutes.
Study patients were monitored with telemetry during their hospital stay and were assessed seven days after discharge by a visiting nurse (vital signs in all and single lead EKG in 68%). Sixteen of 64 patients in the amiodarone group (24%) developed postoperative atrial fibrillation, as compared to 32 of the 60 patients in the placebo group (53%) (P = 0.003). Patients in the amiodarone group were hospitalized for significantly fewer days (6.5 ± 2.6 vs 7.9 ± 4.3 days) (P = 0.04). There was no significant difference in non-fatal or fatal complications between the groups, and hospitalization costs were reduced in the amiodarone-treated patients ($18,375 ± $13,863 vs $26,491 ± $23,837).
COMMENT BY MARK T. GLADWIN, MD
Atrial fibrillation is a common, pesky, and costly complication of cardiac surgery. In fact, approximately one-third of all patients will develop atrial fibrillation after CABG with a peak incidence on day 2 and 3 (Aranki SF, et al. Circulation 1996;94:390-397). Trials with beta-blockers (propranolol, timolol, atenolol, acebutolol, nadolol, and sotolol) given preoperatively or immediately postoperatively have demonstrated a reduction in atrial fibrillation rates. However, these results must be interpreted with caution because 47-93% of patients in the placebo arms of these studies were on beta-blockers preoperatively, and the withdrawal of beta-blockade upon study entry may have contributed to the higher incidence of atrial fibrillation in the placebo arms (Frost L, et al. Int J Cardiol 1992;36:253-261). Furthermore, many patients were excluded from these studies due to heart failure or obstructive pulmonary disease. It is clear from these studies that patients on beta-blockers prior to CABG should have this therapy continued postoperatively.
Amiodarone is classified as a class III antiarrhythmic agent but actually has a wide spectrum of antiarrhythmic effects in atrial and ventricular myocardial cells. It has calcium-channel-blocking and antiadrenergic effects that slow atrioventricular conduction, dilate coronary arteries, and dilate peripheral arterioles (reducing afterload and mildly increasing cardiac output). It is efficacious in both intravenous and oral formulation in converting supraventricular and ventricular tachyarrhythmias, and data mounts supporting the use of rapid intravenous infusion to treat life threatening or refractory ventricular dysrhythmias. The incidence of side effects is related to total drug accumulation and is minimal with short-term treatment, as is the case in the current study by Daoud and associates. Proarrhythmic effects of amiodarone are minimal, but it will decrease cytochrome P-450 activity, resulting in increased levels of digoxin, quinidine, procainamide, warfarin, and cyclosporin (Desai AD, et al. Ann Intern Med 1997;127:294-303).
The current study by Daoud et al suggests that preoperative oral amiodarone therapy will dramatically reduce the incidence of postoperative atrial fibrillation after CABG and valvular surgery and reduce hospital length-of-stay and cost. It is not clear what elements were responsible for the increased length of hospitalization in patients with atrial fibrillation since overall complications were the same in both groups. There was no noted increase in morbidity nor mortality with amiodarone therapy; however, the study was not powered to measure a difference in these end points. Further studies are needed to clarify the appropriate management of patients who do develop atrial fibrillation after cardiac surgery, particularly in those that break through prophylactic therapy.
Which of the following statements is true?
a. Beta-blocker therapy should be discontinued prior to CABG.
b. Amiodarone is contraindicated in patients with mild heart failure.
c. Doses of warfarin and digoxin should be adjusted in patients on amiodarone.
d. Pulmonary toxicity is a common complication of short-term prophylactic amiodarone therapy.
e. All of the above.
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