SPECIAL ARTICLE Practical Guidelines for Clinicians Who Treat Patients With Amiodarone Nora Goldschlager, MD; Andrew E. Epstein, MD; Gerald Naccarelli, MD; Brian Olshansky, MD; Braman Singh, MD; for the Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology miodarone has become an important drug for the treatment of supraventricular and ventricular arrhythmias, in short-term inpatient and outpatient settings. It may also have a role in affecting outcome in patients at high risk for arrhythmic events and sudden death; its place among available therapies is being established in clinical trials. A Arch Intern Med. 2000;160:1741-1748 Patterns of use of amiodarone are not uni- fibrillation (VF) or ventricular tachycar- form, either in academic or in community dia (VT) with hemodynamic instability. settings; overuse and underuse are likely This indication includes the stipula- real phenomena, although data are sparse tion that the arrhythmias are not respon- and largely anecdotal. Guidelines for phy- sive to other available antiarrhythmic sicians who use amiodarone are unavail- agents or that the patients are intolerant able. Because of the potential for serious of them. toxicity with its use, knowledge of drug dos- It is the consensus of this committee ing, beneficial effects, and adverse effects that amiodarone should be used as the an- is essential for proper patient manage- tiarrhythmic agent of choice, in connec- ment. This guideline was created as an ap- tion with other therapies (eg, b block- proach to the use of amiodarone in clini- ers), in patients with sustained ventricular cal practice. The guideline reviews the tachyarrhythmias who have structural indications for use of amiodarone and meth- heart disease, especially left ventricular ods of initiation of therapy, suggests strat- dysfunction, and who are not candidates egies for the follow-up of patients receiv- for an implantable cardioverter-defibrilla- ing amiodarone, and outlines the adverse tor (ICD). This recommendation is based effects of therapy. on the following: (1) 2-year efficacy rates The recommendations contained in reducing arrhythmic events by more herein are based on the best available data than 60%; (2) minimal negative inotro- or, where these are lacking, the collective pic effects and a low incidence of associ- experience of the members of the writing ated proarrhythmia; (3) long-term safety committee. in patients after experiencing a myocar- dial infarction (as demonstrated in the Eu- INDICATIONS FOR USE ropean Myocardial Infarct Amiodarone Trial [EMIAT]1 and the Canadian Amio- Oral Amiodarone darone Myocardial Infarction Arrhyth- mia Trial [CAMIAT]2) and in patients with Oral amiodarone is approved by the Food significant left ventricular dysfunction and Drug Administration for the treat- (as shown in the Grupo de Estudio de la ment of life-threatening recurrent ven- Sobrevida en la Insuficiencia Cardiaca en tricular arrhythmias, such as ventricular Argentina trial [GESICA]3 and the Sur- vival Trial of Antiarrhythmic Therapy in Congestive Heart Failure [CHF-STAT]4); From the Cardiology Division, University of California, San Francisco, San Francisco and (4) efficacy rates for empirical use of General Hospital. A list of all members of the Practice Guidelines Subcommittee, North amiodarone, which are superior to elec- American Society of Pacing and Electrophysiology, appears on page 1747. trophysiologically guided therapy with (REPRINTED) ARCH INTERN MED/ VOL 160, JUNE 26, 2000 WWW.ARCHINTERNMED.COM 1741 Downloaded from www.archinternmed.com , on January 24, 2006 ©2000 American Medical Association. All rights reserved. class 1 antiarrhythmic agents (shown 60% of patients during a 2- to 3-year for this use. However, since acutely in the Cardiac Arrest in Seattle: Con- period. Given its safety profile, administered IV amiodarone has ventional vs Amiodarone Drug especially in patients after a myo- little effect on atrial refractory peri- Evaluation [CASCADE] trial5). cardial infarction and in patients ods, placebo-controlled trials12 have Several prospective trials (An- with heart failure, amiodarone demonstrated no increase in effi- tiarrhythmics Versus Implantable should be considered to be one of cacy in converting atrial fibrilla- Defibrillators [AVID],6 Cardiac Ar- the drugs of choice in maintaining tion to sinus rhythm. One recent rest Study Hamburg [CASH],7 and sinus rhythm in patients with par- study suggests that IV amiodarone Canadian Implantable Defibrillator oxysmal atrial fibrillation. In pa- may minimize the occurrence of Study [CIDS]8) have demonstrated tients without structural heart dis- atrial fibrillation in patients who that an ICD is superior to empirical ease, amiodarone should be used if have undergone an aortocoronary amiodarone therapy in preventing their atrial fibrillation is refractory bypass.13 Further trials should verify sudden cardiac death. Moreover, the to other agents or if the patient is these findings before routine pro- AVID trial6 showed improvement in intolerant of them. phylactic use of amiodarone can be overall survival. Of patients who have Although preoperative oral recommended. ICDs, 30% to 70% require concomi- amiodarone loading has been re- tant antiarrhythmic treatment. Amio- ported to significantly reduce the in- DRUG DOSING darone is effective in slowing the rate cidence of atrial fibrillation after aor- of VT, as tested in the electrophysi- tocoronary bypass surgery,9 this Amiodarone appears to have an un- ology laboratory; this effect appears management strategy has not been paralleled efficacy, a broad spec- to be predictive of a better outcome. widely accepted because of the wide- trum of antiarrhythmic action, and Although amiodarone can increase spread use of b blockers, logistical a complex array of adverse effects the defibrillation threshold, necessi- preoperative loading dose issues, and when used as an antiarrhythmic and tating ICD retesting once the drug has cost. antifibrillatory compound. Some been initiated, it may be useful for pa- knowledge of its pharmacodynam- tients refractory to, or who are not Intravenous (IV) Amiodarone ics, electropharmacologic features, candidates for, sotalol hydrochlo- and pharmacokinetics is essential as ride or other b-blocker therapy. In Intravenous amiodarone has been a basis for initiating therapy in the cases of extremely elderly or criti- approved by the Food and Drug Ad- hospital or in the outpatient setting cally ill patients in whom an ICD ministration for the treatment and and for its safe and effective use might not be appropriate, amioda- prophylaxis of recurrent VF and he- during long-term therapy. rone should be used as first-line modynamically unstable VT in pa- The complexity of the electro- therapy in hemodynamically un- tients refractory to other therapy. pharmacologic profile of amioda- stable sustained VT. The role of elec- This indication is supported by 2 rone is striking.14 The drug length- trophysiologic testing in patients re- prospective, randomized, parallel, ens repolarization, but it is not just ceiving amiodarone is controversial, dose-response studies10,11 that dem- another class 3 antiarrhythmic agent; and remains to be clarified. onstrated a favorable trend toward it exhibits all 4 electrophysiologic Although patients with non- a decrease in VT or VF events per classes of action. Its sodium chan- sustained VT and left ventricular hour and time to the first VT or VF nel–blocking action is seen largely dysfunction are recognized to be at event. Significantly fewer supple- at rapid heart rates but is not asso- increased risk for sudden cardiac mental infusions were required in ciated with the proarrhythmic ef- death, treatment of these arrhyth- patients receiving IV amiodarone, fect typical of class 1 agents. Unlike mias is controversial. In the CHF- 1000 mg/d, compared with those re- the class 1 drugs, it neither in- STAT4 and the GESICA trial,3 use ceiving smaller doses. creases mortality nor depresses ven- of amiodarone had neutral overall Intravenous amiodarone was tricular function; in fact, it in- effects on mortality in patients reported to have comparable effi- creases left ventricular ejection with ischemic cardiomyopathy and cacy to IV bretylium tosylate in one fraction in patients with heart fail- improved survival in those with study11; the mortality rate was not ure. Its class 2 or antiadrenergic ac- nonischemic cardiomyopathy. Based affected. Intravenous amiodarone is tions resemble those of b blockers on these studies, the consensus of also approved to treat patients with but without their adverse effects, in this committee is that it is reason- VT or VF who are candidates for oral part because its b-blocking activity able to use amiodarone in patients amiodarone but are transiently un- is relatively weak. It differs from all with significant left ventricular dys- able to take the oral preparation. other class 3 agents in (1) rarely function and nonsustained VT that In critically ill patients who de- producing torsade de pointes is symptomatic or concerning velop atrial fibrillation with rapid despite markedly lengthening the enough to warrant treatment. ventricular response, IV amioda- QT interval and (2) maintaining its Although not Food and Drug rone has been found to be effective efficacy at rapid heart rates. The Administration–approved for use in in controlling the ventricular rate compound can be administered atrial fibrillation, oral amiodarone is through its short-term