DIAGNOSIS AND TREATMENT
Amiodarone: Reevaluation of an Old Drug
Philip J. Podrid, MD
• Purpose: To review the pharmacology, electrophys-
iology, and toxicity of amiodarone and to discuss the
clinical results produced when amiodarone is used as
therapy for patients with atrial fibrillation, patients with
nonsustained ventricular tachycardia and cardiomyop-
athy, patients who have recently had myocardial infarc-
tions, and patients who have survived out-of-hospital
cardiac arrest caused by ventricular tachycardia or
ventricular fibrillation.
• Data Sources: Animal and clinical studies involving
the pharmacology and electrophysiology of amioda-
rone and clinical trials in which amiodarone was used
as therapy for the arrhythmias noted above were re-
viewed.
• Study Selection: Relevant studies that reported on
the efficacy and toxicity of amiodarone and on long-
term therapy using amiodarone were reviewed, and
their data were summarized. Reports of ongoing trials
using amiodarone were also reviewed and summarized.
• Results: Amiodarone is useful for the treatment of
many rhythm disturbances. Although side effects from
this agent are common, serious toxicity necessitating
discontinuation of therapy is infrequent. Unlike other
antiarrhythmic agents, amiodarone has not been
shown to increase mortality in any population studied.
• Conclusion: Amiodarone, a unique antiarrhythmic
agent with many pharmacologic actions, is effective in
the treatment of a wide range of rhythm abnormalities.
Several large, randomized trials will provide further
information about the clinical usefulness of this agent.
Ann Intern Med. 1995;122:689-700.
From Boston University School of Medicine, Boston, Massachu-
setts. For the current author address, see end of text.
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I n most patients, therapy for arrhythmia involves the
administration of antiarrhythmic agents, but recent devel-
opments have mandated a reassessment of these agents.
Several studies have highlighted the potential risks of
pharmacologic therapy, and, with the availability of new
methods of treatment, disenchantment with antiarrhyth-
mic drugs has been growing. Despite this concern, phar-
macologic therapy has an important role in the manage-
ment of arrhythmia, and the benefits and risks of this
therapy must be considered for the individual patient.
Over the past few years, emerging data have created
much concern about the potential hazards of antiarrhyth-
mic drugs. The Cardiac Arrhythmic Suppression Trial
(CAST) (1, 2) reported the harmful effects of flecainide,
encainide, and moricizine in patients with ventricular pre-
mature beats who had had myocardial infarction. Com-
pared with placebo, flecainide, encainide, and moricizine
were associated with increased mortality from sudden car-
diac death. In an earlier, noncontrolled trial (3), mexil-
etine was also associated with a trend toward increased
mortality. In meta-analyses of studies of quinidine as ther-
apy for nonsustained ventricular tachycardia and preven-
tion of atrial fibrillation (4, 5), drug therapy was associ-
ated with increased mortality when compared with
placebo or with no therapy. Such studies have resulted in
growing therapeutic nihilism on the part of many physi-
cians.
In contrast to many antiarrhythmic drugs, amiodarone
has been reported to be effective in several patient pop-
ulations and is not associated with increased mortality.
Although in the United States amiodarone is currently
indicated only for life-threatening ventricular arrhythmias
refractory to other agents, it is highly effective for the
suppression and prevention of other arrhythmias (6-8).
Of concern, however, has been the toxicity associated with
this agent. Many patients have some side effects, but
these are generally mild; serious toxicity involving the
liver, lungs, and thyroid is infrequent and can usually be
predicted with close monitoring and careful follow-up.
Unlike the other antiarrhythmic agents, amiodarone ad-
ministered orally has resulted in only isolated reports of
arrhythmia aggravation (9, 10). This aggravation has usu-
ally occurred in patients with concomitant hypokalemia or
in patients receiving another antiarrhythmic agent, partic-
ularly a class IA drug. No studies involving patients with
arrhythmia have shown amiodarone to be associated with
increased mortality. Therefore, in view of the growing
concern about class I antiarrhythmic drugs, it seems rea-
sonable that the benefits, risks, and therapeutic role of
amiodarone be reassessed. Unfortunately, few well-con-
trolled trials have compared amiodarone with placebo,
other drugs, or nonpharmacologic therapy. Controlled tri-
als are now in progress and should provide important
data. However, in this paper, I review available data
about the pharmacology, electrophysiology, and toxicity of
© 1995 American College of Physicians 689
 amiodarone and discuss the use of this agent in the
treatment of atrial fibrillation and flutter; the treatment of
nonsustained ventricular tachycardia in patients with car-
diomyopathy and congestive heart failure; the treatment
of patients who have recently had myocardial infarction;
and the prevention of recurrent sustained ventricular
tachycardia and ventricular fibrillation.
Electrophysiologic Actions and Pharmacologic Properties
Amiodarone is a unique and complex drug that was
originally used as an antianginal agent because it is a
potent vasodilator and significantly slows heart rate (11).
Although it is still used for this purpose, especially in
patients with refractory angina who are not candidates for
revascularization (12), amiodarone has gained wider use
as an antiarrhythmic agent (13) because of its various
pharmacologic actions on the heart (14). Its most impor-
tant direct electrophysiologic effect is prolongation of the
action potential duration and repolarization time; this
prolongation results from inhibition of the potassium ion
fluxes that normally occur during phases 2 and 3 of the
action potential (15) and from prolongation of the refrac-
tory periods. These actions represent the class III activity
of amiodarone and occur in all cardiac tissue. The in-
crease in the duration of repolarization and refractoriness
reduces membrane excitability; this reduction represents
the antifibrillatory property of amiodarone. Most class III
antiarrhythmic drugs have a property called "reverse-use
dependency," which causes the action potential duration
(QT interval or repolarization time) to become progres-
sively shorter as heart rate increases. However, amioda-
rone does not have this property; the prolongation of
repolarization time that amiodarone causes persists at
higher heart rates (16). Amiodarone is also a weak so-
dium channel blocker and, as a result of its class I anti-
arrhythmic activity, slows the upstroke velocity of phase 0
of the action potential (17). This reduces the rate of
membrane depolarization and impulse conduction. Amio-
darone also directly depresses the automaticity of the
sinus and atrioventricular nodes.
In addition to these direct antiarrhythmic effects, amio-
darone has several important actions, including j8-block-
ade, that indirectly affect the electrophysiologic properties
of the myocardium. Unlike blockade using the standard
j3-blocking agents, amiodarone's blockade of the /3-adren-
ergic receptors is noncompetitive and results from inhibi-
tion of adenylate cyclase formation and from a reduction
in the number of ]8-adrenergic receptors (18). Amioda-
rone also shows noncompetitive a-blocking activity and
inhibits the slow inward calcium-ion current. Lastly, it is
possible that some antiarrhythmic actions of amiodarone
result from its antithyroid effect: The drug interferes with
thyroid metabolism and with the effects of thyroxin on the
heart (19). It is important to note that amiodarone con-
tains two iodine molecules and that 37.5% of the drug's
weight is iodine (75 mg iodine/200 mg amiodarone).
Hemodynamic Effects
Because of its numerous pharmacologic actions, amio-
darone causes many important hemodynamic effects (14,
20). As a result of its direct effect on smooth muscle and
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its calcium channel and a-adrenergic receptor blockade,
amiodarone dilates coronary arteries and increases coro-
nary blood supply. It also causes peripheral arterial vaso-
dilation and decreases systematic blood pressure and af-
terload. Amiodarone has mild direct negatively inotropic
actions and reduces the force of myocardial contraction;
however, this is offset by the drug's peripheral vascular
effects, primarily afterload reduction, and stroke volume
and cardiac output are generally maintained (20). As
previously indicated, the drug slows the sinus rate through
direct effects on automaticity, antisympathetic action, and
inhibition of slow inward calcium-ion currents. The hemo-
dynamic properties of amiodarone make it understand-
able that the drug was first used as an antianginal agent.
Pharmacokinetics
The gastrointestinal absorption of amiodarone is slow
and incomplete: A peak serum level is achieved 4 to 7
hours after an oral dose is received (21). Only 50% of the
administered dose is bioavailable because of first-pass in-
testinal mucosal and hepatic metabolism as well as incom-
plete absorption. Amiodarone is highly protein- and lipid-
bound and is widely distributed throughout all adipose
tissue (22). As a result of the drug's avid affinity for
adipose tissue, the estimated volume of distribution is 50
L, and approximately 15 g are necessary to saturate these
large body stores. For these reasons, a long and variable
loading period is necessary before antiarrhythmic activity
is apparent.
Clearance of amiodarone involves deiodination, but the
major route of elimination is by hepatic metabolism to
one principal metabolite, desethyl-amiodarone, which has
antiarrhythmic activity equivalent to that of the parent
drug (23). It has been reported that a serum concentra-
tion of at least 1 to 2 /Ltg/mL is necessary for drug efficacy,
but there is wide interpatient variability in the dose-
concentration relation and in levels associated with effi-
cacy or toxicity. Therefore, amiodarone levels in the blood
have limited clinical usefulness. The elimination half-life
of amiodarone is also highly variable but long, ranging
from 16 to 180 days (mean, 52 days), because of the
drug's extensive storage and avid binding to poorly per-
fused adipose tissue (22).
Because of the unique pharmacokinetic properties of
amiodarone, the onset of the drug's action is delayed and
may not be apparent for as long as 3 months. When
administered orally, a loading dose of the drug is re-
quired. The dose used depends on the arrhythmia being
treated, the need to achieve efficacy more quickly, and the
occurrence of side effects, some of which are associated
with higher doses. For the treatment of ventricular
tachyarrhythmias, a recommended dosing schedule is 1200
to 1800 mg/d for 1 to 2 weeks, then 800 mg/d for 2 to 4
weeks, then 600 mg/d for 1 month, and 200 to 400 mg/d
thereafter. For the treatment of supraventricular arrhyth-
mia, the initial dose is 600 to 800 mg/d for 4 weeks, 400
mg/d for 2 to 4 weeks, and 200 mg/d thereafter. However,
the actual duration of loading and the optimal dose used
vary for individual patients and depend on efficacy and
toxicity.
Although not yet approved for use in the United States,
an intravenous preparation of amiodarone may be helpful
 for the acute management of life-threatening ventricular
arrhythmias, especially when other intravenous therapies
have failed (24, 25). The drug is administered as a rapid
infusion of 5 mg/kg body weight over 15 to 30 minutes
and is followed by 1 g/24 h thereafter. Although there are
no absolute guidelines for predicting the onset of drug
activity or the time required for evaluating its effect, the
onset of typical electrocardiographic changes associated
with amiodarone is helpful. These changes include sinus
bradycardia, lengthening of the PR interval, prolongation
of the QT interval, and development of a prominent U
wave not associated with hypokalemia.
Toxicity
Amiodarone is a highly effective antiarrhythmic agent,
but it is associated with many side effects involving many
different organ systems (26, 27). Although as many as
80% of patients have some side effects, only 10% to 15%
of patients require withdrawal of the drug because of
serious or disturbing toxicity. The mechanism of toxicity is
multifactorial and may result from the accumulation of
substances such as iodine or amiodarone itself; the devel-
opment of cellular phospholipidosis secondary to phos-
pholipase inhibition; the formation of free radicals; al-
tered cellular function; or immunologic injury (28). Most
side effects are not dose-related and occur only after
weeks or months of therapy, as a result of the pharma-
cologic properties of amiodarone. It has been observed
that the incidence of side effects increases over time and,
therefore, that many side effects may be related to the
total dose administered or the total dose given over time,
that is, to the amount of drug that has accumulated.
Cardiovascular Toxicity
Signs of cardiovascular toxicity include accentuation of
the normal electrophysiologic actions of the drug, specif-
ically sinus bradycardia; conduction abnormalities in the
atrioventricular node; and heart block. Because amioda-
rone has negatively inotropic actions, congestive heart
failure may occur; the reported incidence of congestive
heart failure in patients treated with amiodarone is 2% to
3%. When amiodarone is given intravenously, hypoten-
sion unrelated to dose is seen in about 28% of patients
(24, 25). Like all antiarrhythmic drugs, amiodarone can
aggravate arrhythmia; this is reported in 3% to 5% of
patients (29). However, because of the long time course
of drug action, it may be difficult to distinguish between
the natural history of the underlying cardiac disease and
the arrhythmia and a drug-related aggravation of arrhyth-
mia. Although amiodarone markedly prolongs the QT
interval, torsade de pointes is an infrequent complication
and is most often reported in association with hypokale-
mia or with concomitant therapy using a class LA drug,
especially quinidine (9, 10). Amiodarone may increase the
threshold energy for defibrillation or cardioversion; this is
especially important when an implantable defibrillator is
present (30).
Pulmonary Toxicity
The most serious noncardiac side effect of amiodarone
is pulmonary toxicity, which has been reported in as many
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as 15% of patients, although the overall incidence is
about 6% to 8% (26). The pathogenesis of this toxicity is
multifactorial but may be dose-related and appears to be
more common in patients with underlying lung disease.
Pulmonary toxicity may occur within the first few weeks of
therapy and presents with an acute onset of nonspecific
symptoms, including fever, shortness of breath, and
cough, which are probably symptoms of a hypersensitivity
reaction to the drug and are associated with an eosino-
philic lung infiltrate. More common is a delayed pulmo-
nary reaction occurring after several months or years of
therapy. This reaction is generally insidious in onset and
associated with nonspecific cough, fatigue, low-grade fe-
ver, and shortness of breath, or it may be more acute,
presenting with respiratory failure (31). Chest radiographs
show diffuse monocellular infiltrates or diffuse and exten-
sive pulmonary fibrosis. Pleural effusions may also be
present. This toxic response has been confused with con-
gestive heart failure and pneumonia, and, if the correct
diagnosis is missed or delayed, respiratory failure and
death can occur. Although discontinuation of amiodarone
therapy is mandatory, pulmonary toxicity can persist for
weeks or months and may actually initially progress as a
result of the large stores of the drug in the body, the
drug's long half-life, and the prolonged time needed for
elimination. Steroids may increase the rate of resolution
(32). Unfortunately, pulmonary function tests are not pre-
dictive of pulmonary toxicity because their results are
almost always abnormal in patients receiving amiodarone.
Most often seen is a reduced diffusion capacity similar to
that of a restrictive lung disease. The chest radiograph is
the best screening technique for this complication.
Thyroid Abnormalities
Abnormalities of the thyroid occur in 30% of patients
(26); this is not unexpected because amiodarone has sub-
stantial iodine content. The drug interferes with the con-
version of thyroxine to triiodothyronine, which is the ac-
tive form of thyroxin (19). The abnormalities are usually
minor, particularly the elevation of thyroid-stimulating
hormone levels. Clinically important hypothyroidism and
hyperthyroidism have each been reported in 5% to 10%
of patients (26).
Gastrointestinal Side Effects
Commonly seen during the initial period of loading,
gastrointestinal side effects may be dose-related and in-
clude nausea, vomiting, anorexia, abdominal discomfort,
and constipation. Altered taste is also reported. Abnor-
malities on liver function tests, especially elevated amino-
transferase and alkaline phosphatase levels, are seen in
25% of patients. Hepatitis is rare and may be related to
prolonged therapy with a high dose. Liver failure and
death have been reported.
Dermatologic Side Effects
These side effects are common and include an allergic
rash, photosensitivity, and an unusual blue-gray skin dis-
coloration. Hair loss has been infrequently reported.
691
 Table 1. Amiodarone for Atrial Fibrillation or Atrial Flutter

Study (Reference) Patients, n Follow-up, mo Patients in Whom Patients with Patients with Side
Amiodarone was Side Effects, % Effects
Effective, % Necessitating
Totally Partially Discontinuation, %

Rosenbaum et al. (13) 30 Unknown 97 ~ _ _

Ward et al. (35) 21 3 to 60 57 24 44 15
Graboys et al. (6) 95 27 78 6 30 7
Haffajee et al. (36) 71 10 76 - 30 9
Peter et al. (37) 42 22 57 24 - -
Gold et al. (38) 68 21 79 - 35 10
Brodsky et al. (39) 25 22 40 44 24 12
Mostow et al. (40) 15 - 63 - 42 0
Fogoros et al. (7) 15 8 65 - - -
Crijns et al. (41) 34 12 40 - - 6
Horowitz et al. (42) 38 15 53 18 35 16
Yee et al. (43) 55 3 69 - - -
Gooselink et al. (44) 89 21 61* 17 1
56t
53$

* After 1 year.
t After 2 years.
$ After 3 years.

Neurologic Toxicity or atrioventricular nodal function and enhancement of the

negatively inotropic effects of these blocking agents.
Tremor, ataxia, peripheral neuropathy, fatigue, and
weakness may all result from neurologic toxicity. These
side effects are often dose-related and are more com- Clinical Use of Amiodarone for Management of
monly reported during the loading period. They may also Arrhythmia
be seen if high doses of the drug are continued over long
periods. Atrial Fibrillation and Flutter

Amiodarone exerts significant effects on atrial tissue

Ophthalmologic Side Effects
Corneal microdeposits, caused by the secretion of
amiodarone by the lacrimal gland with accumulation on
the corneal surface (33), are among the ophthalmologic
side effects of amiodarone therapy. These deposits are
almost universal and usually do not cause visual distur-
bances, but, if they are heavy, they can cause corneal cysts
and abscesses. Macular degeneration has been observed,
but the relation of this degeneration to amiodarone re-
mains uncertain.
Drug Interactions
Amiodarone frequently interacts with other drugs (34).
One of the most common interactions is with warfarin;
amiodarone can potentiate the effect of this drug by in-
terfering with hepatic metabolism. The prothrombin time
is elevated, necessitating a reduction in the warfarin dose.
This interaction may be erratic; hence, frequent measure-
ment of the prothrombin time, especially during the first
few weeks of loading, is essential. Because amiodarone
can elevate the serum digoxin level, reduction of the digoxin
dose may be necessary. Amiodarone may also increase the
serum level of other antiarrhythmic drugs, including quini-
dine, procainamide, mexiletine, and propafenone. When
combined with class IA drugs, amiodarone may cause an
exaggerated QT prolongation, increasing the risk for torsade
de pointes. Potentiation of the effects of anesthetic agents,
including hypotension and bradycardia, has been reported.
The combined use of amiodarone and j3-blockers or calcium
channel blockers may result in marked depression of sinus
and, as expected, is effective for the treatment of atrial
arrhythmias, particularly atrial fibrillation and atrial flutter
(6, 7, 13, 35-44). Currently, the most effective therapy for
these arrhythmias is pharmacologic, and, as seen in Table
1, amiodarone is completely or partially effective for the
prevention of atrial fibrillation or flutter in approximately
80% of patients. This can be compared with the approx-
imate 50% rate of sinus rhythm maintenance seen at 1
year when class I drugs, particularly quinidine, are used
(44). In a study of low-dose amiodarone, Gosselink and
colleagues (44) found that with a dose of 200 mg/d, 53%
of patients remained in sinus rhythm at 3 years. Among
patients with severe left ventricular dysfunction, 93% re-
mained in sinus rhythm. It is important that the use of
low-dose amiodarone was associated with a low incidence
of side effects (17%) and that proarrhythmia was not
seen. Only one patient died; the death was unrelated to
use of the drug. These results contrast markedly with
those of class I drugs (4).
Only a few randomized trials have compared amioda-
rone with other therapies for atrial fibrillation. Zehender
and coworkers (45) randomly assigned 40 patients with
atrial fibrillation (present for > 4 weeks but < 2 years) to
receive therapy with amiodarone, quinidine, or quinidine
plus verapamil. Sinus rhythm was restored in 25% of
patients receiving quinidine, in 55% of patients receiving
quinidine and verapamil, and in 60% of patients receiving
amiodarone. Unfortunately, long-term efficacy data are
not available from this study because, at the end of 3
months, patients receiving amiodarone were switched to
quinidine and verapamil. Vitolo and coworkers (46) ran-

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 domly assigned 54 patients to receive quinidine or low-
dose amiodarone. At 6 months, more patients in the
group receiving amiodarone than in the group receiving
quinidine were in sinus rhythm (79% compared with 40%;
P = 0.01). Similar results were reported by Martin and
colleagues (47) in a study of 70 patients randomly as-
signed to receive disopyramide or amiodarone. Although
these small, short-term studies indicate that amiodarone
is effective and safe for the prevention of atrial fibrilla-
tion, long-term controlled trials comparing amiodarone
with other drugs or other approaches to therapy are not
available. On the basis of studies in the literature, Disch
and coworkers (48) used a Markov decision analysis to
compare four strategies for the management of atrial
fibrillation: no therapy; warfarin and rate control; electri-
cal cardioversion and quinidine maintenance therapy; and
electrical cardioversion followed by low-dose amiodarone
therapy. When this analysis was used in a hypothetical
cohort of patients with atrial fibrillation who were be-
tween 65 and 70 years of age, the percentage of patients
with disabling events was lower with amiodarone (1.4%)
than with quinidine (1.8%), warfarin and rate control
(2.6%), or no therapy (7.4%). Moreover, the 5-year mor-
tality rate was lower with amiodarone (13.6%) than with
warfarin and rate control (14.4%), quinidine (15.2%), or
no therapy (18.2%). In this analysis, amiodarone therapy
was the preferred strategy.
Amiodarone prevents episodes of paroxysmal atrial fi-
brillation or flutter. It only infrequently reverses chronic
or sustained arrhythmia, but it prevents recurrence of
arrhythmia after electrical cardioversion, especially if the
duration of atrial fibrillation before therapy was less than
1 year. In most studies reporting on clinical predictors of
drug efficacy, the response to amiodarone has been unre-
lated to left atrial size; this is in contrast to that which has
been observed with some other agents. Side effects caused
by amiodarone have been reported in 35% of patients
with atrial fibrillation, but the effects in most cases are
mild. Discontinuation of amiodarone therapy is necessary
in only 9% of patients. Among patients with atrial fibril-
lation and flutter, aggravation of arrhythmia or increased
mortality as a result of therapy have not been reported.
Generally, the effective dose of amiodarone is low, often
200 mg/d or less, which probably accounts for the low
incidence of serious side effects and the high degree of
patient tolerance.
Although amiodarone is also effective for preventing
atrioventricular nodal reentrant tachycardia, radiofre-
quency ablation is a useful approach that is widely used as
a first-line therapy (49, 50). Similarly, amiodarone is ef-
fective for preventing atrial tachyarrhythmias (atrial fibril-
lation, atrial flutter, and atrioventricular reentrant tachy-
cardia) in patients with the Wolff-Parkinson-White syndrome
(51). However, ablation of the accessory pathway has be-
come a preferred therapy (52, 53).
Recommendations for Use in Atrial Fibrillation
Although it is effective for atrial fibrillation, amioda-
rone is not approved for this indication. Most physicians
prefer conventional antiarrhythmic drugs (class IA or IC)
for initial therapy to prevent atrial fibrillation. If arrhyth-
mia recurs despite these agents, therapeutic options are
maintenance of atrial fibrillation as the rhythm of choice,
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use of atrioventricular nodal blocking drugs for rate-slow-
ing and anticoagulation, and amiodarone for prevention.
A decision about the best approach needs to be made for
each individual patient on the basis of the benefits and
risks of chronic atrial fibrillation compared with the ben-
efits and risks associated with long-term amiodarone ther-
apy. For some patients, such as those with a cardiomyop-
athy and poor left ventricular function, prevention of
atrial fibrillation is important for hemodynamic stability.
In such patients, amiodarone may be the preferred initial
therapy because other agents are less effective and are
associated with a substantial risk for cardiac toxicity.
Amiodarone is often well tolerated and is effective for
maintaining sinus rhythm in these patients.
Postmyocardial Infarction
Several studies involving patients who have had myo-
cardial infarction have found that ventricular arrhythmia,
primarily runs of nonsustained ventricular tachycardia in
association with left ventricular dysfunction, is an inde-
pendent risk factor for sudden death during follow-up
(54, 55). Unfortunately, no data show that suppression of
arrhythmia with standard antiarrhythmic drugs will reduce
mortality from sudden death. Although in most of the
trials of drugs for arrhythmia after myocardial infarction,
investigators did not give therapy to suppress arrhythmia,
CAST did involve the suppression of arrhythmia with an
antiarrhythmic drug (1). In this study, mortality from sud-
den death was significantly increased by drug therapy
involving encainide, flecainide, and moricizine. Many
large trials involving various ]3-blockers, in contrast, have
shown that therapy with these agents reduces total mor-
tality and mortality from sudden death (56, 57). This
beneficial effect is especially striking in patients with left
ventricular dysfunction and congestive heart failure. A
recent report suggests that verapamil is also beneficial in
patients who have had myocardial infarction and who do
not have congestive heart failure (58). The protective
mechanism of these agents is unknown but is probably
related to their blockade of the effects on the heart of the
sympathetic nervous system and circulating catecholamines.
In fact, the reduction in mortality appears to be related to
the degree to which heart rate is slowed and not to any
direct antiarrhythmic action.
Data show that in patients who have had myocardial
infarction, amiodarone (in contrast to class I drugs) re-
duces the incidence of sudden death due to ventricular
tachyarrhythmia. Three studies have shown that total car-
diac mortality rates and rates of mortality from sudden
death were lower among patients receiving amiodarone
than among those receiving placebo (Table 2) (8, 59, 60).
In the Basel Antiarrhythmic Study of Infarct Survival
(BASIS) (8), patients with multiform or repetitive ventric-
ular arrhythmia (couplets or nonsustained ventricular
tachycardia) that was documented 8 to 24 days after
myocardial infarction were randomly selected to receive
placebo, individualized treatment with various antiar-
rhythmic drugs, or amiodarone. The survival of patients
receiving amiodarone was greater and arrhythmic events
in these patients were fewer than those in patients receiv-
ing placebo or conventional therapy. The beneficial effect
of amiodarone persisted despite discontinuation of ther-
693
 Table 2. Amiodarone for Patients Who Have Had Myocardial Infarction
Study (Reference) Patients, Follow-up,
n mo
Basel Antiarrhythmic Study of Infarct
Survival (8) 312
Amiodarone 98
Individualized therapy 100
Control 114
Canadian Amiodarone Myocardial Infarction
Arrhythmia Trial (59) 77
Amiodarone 48
Placebo 29
Polish trial (60) 613
Amiodarone 305
Placebo 308
*P= 0.048.
t P < 0.07.
apy with the drug after 1 year (61). Total cardiac mortal-
ity after 4 years was lower in the group treated with
amiodarone than in the control group; this was entirely
due to the effect of amiodarone during the first year.
However, in a follow-up analysis of the 212 patients who
had received either amiodarone or no therapy, it was
found that the lower 5-year cardiac mortality rate (1.0%
with amiodarone compared with 8.9% for controls) and
the decrease in arrhythmic events were confined to the
group of patients with a left ventricular ejection fraction
of more than 40%. No significant difference was seen in
patients with an ejection fraction of less than 40% (62).
This differentiates amiodarone from ^-blockers, which
have been reported to be of greater benefit in patients
with left ventricular dysfunction and congestive heart fail-
ure (63).
The Polish trial (60) enrolled 613 patients 5 to 7 days
after myocardial infarction who were not eligible to re-
ceive j3-blockers. Patients were randomly selected to re-
ceive amiodarone (200 to 400 mg/d) or placebo. Amioda-
rone significantly reduced the incidence of nonsustained
ventricular tachycardia (7.5% in patients receiving amio-
darone compared with 29.5% in patients receiving pla-
cebo; P < 0.001). After 1 year of follow-up, total, cardiac,
and sudden death mortality rates were reduced, but the
reduction was not statistically significant.
In the pilot phase of the Canadian Amiodarone Myo-
cardial Infarction Arrhythmia Trial (CAMIAT) (59), 77
patients with acute myocardial infarction who had more
than 10 ventricular premature beats per hour and more
than one run of nonsustained ventricular tachycardia in
24 hours on ambulatory monitoring obtained within 6 to
45 days of the infarction were randomly assigned to re-
ceive amiodarone (300 to 400 mg/d) or placebo. Suppres-
sion of arrhythmia at 2 weeks was greater in the group
treated with amiodarone (85%) than in the group receiv-
ing placebo (27%). After a 2-year follow-up, deaths from
arrhythmia were fewer and all-cause mortality rates were
lower in the group treated with amiodarone. The larger
trial, now in progress, will enroll 1200 patients who will be
followed for 2 years (64). Another trial in patients who
have had myocardial infarction, the European Myocardial
Infarct Amiodarone Trial (EMIAT) (65), is currently in
progress and will randomly assign 1500 patients within 5
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Patients Withdrawn because Mortality Rate ,_%
of Side Effects, % Total Cardiac Sudden
Death
12
- 4 5 1 4*
- 8 10 1 8
- 9 13 1 9*
20
- 35 10 8 6
- 34 21 3 14*
12
- 18 7 6 3
- 6 11 11 7t
to 21 days after acute myocardial infarction to receive
either amiodarone or placebo. The entry criterion is a left
ventricular ejection fraction of less than 40%, and a
3-year follow-up is planned.
Amiodarone has also been compared with j3-blocker
therapy (metoprolol) or with no therapy in patients who
have had myocardial infarction and have nonsustained
ventricular tachycardia and a left ventricular ejection frac-
tion of 20% to 45%; these patients were randomly as-
signed 10 to 60 days after the event to receive metoprolol,
amiodarone, or no therapy (66). The mortality rate at 2.8
years was 3.5% in the 115 patients receiving amiodarone
(200 mg/d), 7.7% in the untreated group, and 15.4% in
the group treated with metoprolol. Amiodarone was more
effective than metoprolol for suppressing ventricular ar-
rhythmia. It is not certain whether this beneficial effect
was due to the class III (antifibrillatory) antiarrhythmic
activity or to the j3- or calcium channel blocking actions
of amiodarone.
Aggravation of arrhythmia involving amiodarone was
seen in CAST but not in any of the trials discussed above.
Unfortunately, the number of patients studied to date is
small and the reduction of the mortality rate is of ques-
tionable clinical importance, especially when compared
with the results of j3-blockade. Nevertheless, these studies
do suggest that administration of amiodarone is safe in
the patient who has had myocardial infarction and who
has an arrhythmia that may require antiarrhythmic ther-
apy.
Recommendations for Use in Patients after Myocardial
Infarction
Although the results of trials using amiodarone after
myocardial infarction are encouraging, prophylactic ther-
apy with j3-blockers is still the preferred treatment for
patients who have had an infarction. Amiodarone may be
an alternative for the patient with a contraindication to
/3-blocker therapy and may be preferred for the patient
who has runs of nonsustained ventricular tachycardia de-
spite treatment with /3-blockers. When sustained ventric-
ular tachycardia or ventricular fibrillation occur in the
period after infarction, amiodarone is a reasonable option
for therapy because it appears to be safe. Amiodarone
may also be the safest therapy for atrial arrhythmia, par-
 Table 3. Amiodarone in Patients with Cardiomyopathy, Congestive Heart Failure, and Ventricular Arrhythmia
Study (Reference) Patients, Dose, Follow-up, Mortality, % Improved Survival
n mg/d mo Control Amiodarone
Cardiac Sudden Cardiac Sudden
Death Death

Neri et al. (71) 65 200 to 400 31 31 15 26 0 Yes

Cleland et al. (72) 22 200 3 14 14 0 0 Yes
Cleland et al. (73) 152 184 20 - 45 - 15 Yes
Nicklas et al. (74)* 101 200 12 19 17 28 24 No
Hamer et al. (75)t 34 200 6 - - - - -
Zehender et al. (76) 30 200 24 - 17 - 0 Yes
Burckhardt et al. (77)$ 34 200 to 400 49 - - 34 21 Yes
Kerin et al. (78)$ 110 200 to 400 15 - - 22 12 Yes
EPASMA 1 (79) 127 400 12 28.6§ 20.4 10.5§ 7.0 Yes (P < 0.02)
Grupo de Estudio de la Sobrevida
en la Insuficiencia Cardiaca en
Argentina (GESICA) (80) 516 300 13 41.4§ 15.2 33.5§ 12.3 Yes (P < 0.024)
(not for sudden
death P = 0.16)
Veterans Affairs Congestive Heart
Failure Antiarrhythmic Trial
(CHF-STAT) (82) 674 200 to 400 36 42|| No

* Among ischemic and nonischemic subsets, mortality rates in the control and drug groups were similar.
t Amiodarone improved left ventricular ejection fraction and decreased ventricular arrhythmia; no other details were given.
$ No control or placebo group.
§ Total mortality.
|| Data incomplete;figuresrepresent total mortality at 3 years for entire study group.

ticularly that caused by atrial fibrillation, in the patient
who has recently had an infarction.
Cardiomyopathy and Ventricular Arrhythmia
Approximately 40% of deaths in patients with a car-
diomyopathy and congestive heart failure are sudden and
are usually the result of a ventricular tachyarrhythmia.
Although their results are still controversial, most studies
have reported that nonsustained ventricular tachycardia,
documented in approximately 40% of patients with car-
diomyopathy and congestive heart failure, is associated
with an increased risk for sustained ventricular tachyar-
rhythmia and sudden death (67, 68). Although the pres-
ence of nonsustained ventricular tachycardia and the risk
for sudden death in these patients appear to be related,
the role of suppression of arrhythmia using conventional
antiarrhythmic drugs in preventing this outcome is un-
known because no well-controlled trials have been done.
Unfortunately, data suggest that antiarrhythmic drugs are
associated with an increased risk for cardiac toxicity in
such patients, particularly a worsening of congestive heart
failure (69) and aggravation of arrhythmia (70).
In contrast, amiodarone has been administered to pa-
tients with cardiomyopathy and ventricular arrhythmia in
several trials, and each found that the drug was effective
for suppressing ventricular arrhythmia (71-80). More im-
portantly, in most of these studies, amiodarone reduced
total cardiac mortality or mortality from sudden death
compared with placebo or historic controls (Table 3). The
relation between the suppression of nonsustained ventric-
ular tachycardia and outcome is still uncertain, but, unlike
other antiarrhythmic agents, amiodarone appears to be
well tolerated in patients with a cardiomyopathy and ven-
tricular arrhythmia, and aggravation of arrhythmia has not
been observed.
These data are preliminary but encouraging. Several
ongoing placebo-controlled trials involving patients with
cardiomyopathy and ventricular arrhythmia are comparing
amiodarone with placebo. The study from the Grupo de
Estudio de la Sobrevida en la Insuficiencia Cardiaca en
Argentina (GESICA) (80) involved patients with class II
to class IV congestive heart failure who had a cardiotho-
racic ratio of more than 0.55, an ejection fraction of less
than 35%, and an end-diastolic echocardiographic diam-
eter of more than 3.2 cm body surface area. Amiodarone
reduced overall mortality compared with placebo (33.5%
compared with 41.4%; P = 0.024); however, when analysis
was done according to cause of death, amiodarone did
not reduce mortality from sudden death (12.3% compared
with 15.2%; P = 0.16) or death from heart failure (16.9%
compared with 20.3%; P = 0.16). Amiodarone reduced
total mortality and admissions for heart failure (45.8%
compared with 58.2%; P = 0.0024). The largest trial, the
Veterans Affairs Congestive Heart Failure Antiarrhythmic
Trial (CHF-STAT) (81), randomized 674 patients with
ischemic or nonischemic cardiomyopathy who had more
than 10 ventricular premature beats per hour. Eligibility
requirements were clinical congestive heart failure, a left
ventricular ejection fraction of less than 40%, a left ven-
tricular internal dimension by echocardiogram of more
than 55 mm, or a cardiothoracic ratio on chest radiograph
of more than 0.5. The dose of amiodarone used was 400
mg/d for 1 year and 200 to 300 mg/d thereafter. In a
preliminary report, amiodarone significantly suppressed
the frequency of ventricular arrhythmia, but all-cause
mortality did not differ between the groups receiving
amiodarone and placebo (82). However, additional defin-
itive data and subset analyses, particularly in patients with
nonsustained ventricular tachycardia, are not yet available
and will provide important information.
Patients with a hypertrophic cardiomyopathy and non-
sustained ventricular tachycardia also have an increased

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 Table 4. Amiodarone for Sustained Ventricular Tachyarrhythmias (Ventricular Tachycardia or Ventricular Fibrillation)

Study (Reference) Patients, Follow-up, Mortality, % Recurrence of Side Drug Withdrawn

n mo Ventricular Effects, because of Side
Total Sudden Tachyarrhythmia, % Effect, %
Cardiac Death %
Heger et al. (86) 45 12 10 7 17 _ 7
Fogoros et al. (7) 77 8 - 11 23 72 15
Horowitz et al. (87) 69 12 - 6 23 - -
Nademanee et al. (88) 40 16 13 5 5 15 3
Podrid et al. (89) 41 10 24 15 0 23 0
Haffajee et al. (36) 96 10 - 5 9 25 10
Peter et al. (37) 77 21 23 13 0 - 4
Heger et al. (90) 196 16 10 8 11 - 11
Morady et al. (91) 154 14 19 12 10 51 10
Greene et al. (92) 66 11 7 7 7 93 19
Veltri et al. (93) 42 22 28 19 5 52 5
DiCarlo et al. (94) 104 15 - 24 15 - 10
Horowitz et al. (95) 100 18 - 21 12 26
Kadish et al. (96) 121 27 - 21 14 24 11
Klein et al. (97) 60 16 - - 13 8 -
Smith et al. (99) 77 24 - 25 22 - 26
Herre et al. (100) 427 60 - - 21 22 37
Meyers et al. (101) 145 39 - 38 14 - 17
Kowey et al. (102) 57 22 - 12 10 12 6

risk for sudden death (83). Some data show that amioda-
rone benefits these patients because it reduces total car-
diac mortality and mortality from sudden death (84). In a
study by McKenna and colleagues (84), 24 patients with
nonsustained ventricular tachycardia were treated with
conventional antiarrhythmic drugs, 21 patients with non-
sustained ventricular tachycardia were treated with amio-
darone, and 123 patients without ventricular tachycardia
were not treated. During a 36-month follow-up, no pa-
tients died in the group treated with amiodarone; the
group receiving conventional drugs had a 21% mortality
rate, and the group without ventricular tachycardia had a
4% mortality rate. However, data from the National In-
stitutes of Health, reported by Fananapazir and col-
leagues (85), indicate that amiodarone may be harmful in
patients with a hypertrophic cardiomyopathy who receive
therapy for relief of hemodynamic symptoms rather than
for suppression of arrhythmia. Fananapazir and col-
leagues prospectively evaluated amiodarone therapy (400
mg/d) in 50 patients with hypertrophic cardiomyopathy
who had hemodynamic symptoms despite treatment with
calcium channel blockers or j3-blockers. McKenna and
colleagues (84) administered amiodarone only to patients
with nonsustained ventricular tachycardia, but only 21 of
the patients (42%) studied by Fananapazir and colleagues
(85) had nonsustained ventricular tachycardia. Although
amiodarone improved the patients' functional status and
exercise duration, 7 sudden deaths occurred during the
mean follow-up of 2.2 years, 6 within the first 5 months of
therapy. As previously reported, survival was worse
among patients who had had nonsustained ventricular
tachycardia before therapy than among those without this
arrhythmia (61% compared with 97% at 2 years; P<
0.01). However, sudden deaths occurred despite suppres-
sion of nonsustained ventricular tachycardia, and all oc-
curred in patients in whom ventricular tachycardia was
absent on ambulatory monitoring at 2 months. Fanana-
pazir and colleagues observed that sudden death was as-
sociated with a decrease in left ventricular filling rate and
suggested that amiodarone had a harmful effect on he-
modynamics in patients with hypertrophic cardiomyopa-
thy. Although these data are disturbing, the patients in
this study differed from those in the study by McKenna
and coworkers: Their therapy was for hemodynamic
symptoms resulting from cardiomyopathy rather than for
symptomatic arrhythmia.
Recommendations for Use in Patients with Nonsustained
Ventricular Tachycardia and Cardiomyopathy
At present, data from noncontrolled trials suggest that
in patients with a cardiomyopathy and ventricular arrhyth-
mia, and particularly in those with nonsustained ventric-
ular tachycardia, amiodarone is effective for suppressing
ventricular arrhythmia and for reducing mortality from
sudden death and cardiac mortality. However, until the
results from the large controlled Veterans Affairs study
are reported, amiodarone cannot be recommended as
therapy for all of these patients. For the patient with a
cardiomyopathy who has frequent and symptomatic epi-
sodes of nonsustained ventricular tachycardia, amioda-
rone is a logical first drug because it appears to be more
effective and safer than other agents. The value of anti-
arrhythmic therapy for patients with asymptomatic non-
sustained ventricular tachycardia remains unproven, but if
therapy is thought to be necessary, amiodarone might be
preferred on the basis of its efficacy and safety.
Sustained Ventricular Tachyarrhythmias
Amiodarone has been used primarily in patients pre-
senting with sustained ventricular tachyarrhythmia, ven-
tricular tachycardia, or ventricular fibrillation refractory to
other pharmacologic agents. In as many as 50% to 60%
of patients, these arrhythmias may be refractory when
therapy is evaluated with electrophysiologic testing. Be-
fore the widespread use of the implantable cardioverter-
defibrillator, amiodarone was the only therapy available
for patients with ventricular arrhythmia refractory to con-

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 ventional antiarrhythmic drugs or for those without ar-
rhythmia induced by electrophysiologic study. Many un-
controlled trials found that amiodarone was effective for
the prevention of recurrence of a serious ventricular
tachyarrhythmia and for prolonging life (Table 4) (36, 37,
86-102). The reported mortality from sudden death
among such patients receiving amiodarone ranges from
3% to 15% per year, and nonfatal arrhythmia occurs in
3% to 25%. Unfortunately, because none of these trials
was controlled, it is unclear whether amiodarone actually
prevents arrhythmia and prolongs life, although most in-
vestigators have recognized that amiodarone is indeed
effective.
It has been reported that amiodarone is effective for
preventing recurrent arrhythmia when efficacy is based on
the suppression of nonsustained ventricular tachycardia
on ambulatory monitoring (89, 103) or prevention of ven-
tricular tachycardia induction in the electrophysiologic
laboratory (97, 100, 101). Unfortunately, it has been ob-
served that amiodarone only infrequently prevents the
induction of sustained ventricular tachycardia, although it
often slows the rate of the induced arrhythmia. It has
been reported that if the ventricular rate is slowed by
more than 100 ms and if the arrhythmia is hemodynam-
ically stable and well tolerated, the survival rate is iden-
tical to that observed among the patients in whom ar-
rhythmia is no longer inducible, although the incidence of
nonfatal recurrence is still substantial. (95, 96).
One randomized trial, Conventional versus Amioda-
rone Drug Evaluation (CASCADE), involved cardiac ar-
rest patients in Seattle (98). A total of 228 patients with
out-of-hospital ventricular fibrillation not caused by myo-
cardial infarction were randomly assigned to receive ther-
apy with amiodarone (mean dose, 183 mg/d) or conven-
tional antiarrhythmic drugs guided by electrophysiologic
study. The cardiac death rate, which included cardiac
mortality, resuscitated cardiac arrest due to ventricular
fibrillation, and syncope resulting in defibrillator shock,
was 18% in the group receiving amiodarone and 31% in
the group receiving conventional therapy at 2 years (P =
0.007). Similarly, patients treated with amiodarone had a
lower incidence of cardiac death and sustained ventricular
tachycardia than those receiving conventional drugs (22%
compared with 48%; P < 0.001). Among the 105 patients
receiving an implantable defibrillator, fewer of those
treated with amiodarone had a syncopal shock (20 com-
pared with 31; P = 0.014).
Although amiodarone appears to be effective for pa-
tients with sustained ventricular tachycardia or fibrillation,
the implantable cardioverter-defibrillator is now widely
used, and many patients who would be candidates for
amiodarone therapy (those with arrhythmias refractory to
other agents or without inducible arrhythmia) are receiv-
ing this device. Results to date with the defibrillator have
been impressive; the reported incidence of sudden death
is 1% to 2% per year (104, 105), although early, in-
hospital deaths related to surgery or other complications
from device implantation are usually not included in such
data (105). Additionally, concern about the beneficial role
of the defibrillator in patients with significant left ventric-
ular dysfunction has arisen because total cardiac mortality
in these patients remains high despite the use of this
device as a result of death from progressive congestive
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heart failure (105-107). Indeed, in a recent study by New-
man and coworkers (106), no difference was seen in sur-
vival at 3 to 4 years between 60 patients receiving the
defibrillator and 120 patients receiving amiodarone. It
should be pointed out that, in this study, the non-sudden-
death rate in patients receiving the defibrillator was sig-
nificantly lower than in those receiving amiodarone (17%
compared with 39%), suggesting that patients receiving
amiodarone were sicker and had worse ventricular func-
tion. The investigators concluded that although the defi-
brillator prevents sudden death, the early survival advan-
tage is lost over time because of death from other cardiac
and noncardiac causes.
A preliminary report from the only randomized trial to
date, the Cardiac Arrest Study Hamburg (CASH) (108),
also suggested that total mortality did not differ signifi-
cantly between a group of patients receiving the implant-
able defibrillator and a group receiving amiodarone. At
present, 230 survivors of sudden death have been ran-
domly assigned to receive an implantable defibrillator,
amiodarone, metoprolol, or propafenone. Although the
rate of sudden death has been lower in the group receiv-
ing the defibrillator (0% compared with 8.6% in the
group receiving amiodarone, 11.4% in the group receiving
metoprolol, and 11.4% in the group receiving propa-
fenone), the total mortality rate was 14.3% in the group
receiving the defibrillator, 14.7% in the group receiving
amiodarone, 14.3% in the group receiving metoprolol,
and 20% in the group receiving propafenone. Total mor-
tality did not differ significantly among the four groups.
However, total mortality and mortality from sudden death
were higher in the group receiving propafenone, and
propafenone has been dropped from the trial.
Survival with long-term amiodarone therapy may be
equivalent to that achieved with the defibrillator, espe-
cially in patients with poor left ventricular function (ejec-
tion fraction < 25%). Similarly, it is possible that patients
with inducible ventricular tachycardia that becomes signif-
icantly slower during amiodarone therapy will have total
and sudden death mortality rates on drug similar to those
achieved with a defibrillator. However, the role of amio-
darone in these patients remains uncertain because no
randomized controlled trials have compared amiodarone
with other antiarrhythmic drugs or with other forms of
therapy, particularly the implantable defibrillator. Also of
concern are the cost-effectiveness of amiodarone therapy
compared with that of the implantable defibrillator and
quality of life with either therapy. Two ongoing studies
are addressing these issues. The Canadian Implantable
Defibrillator Study (CIDS) (109) will randomly assign 400
patients with cardiac arrest or hemodynamically unstable
ventricular tachycardia to receive therapy with amioda-
rone (>300 mg/d) or an implantable defibrillator. The
primary outcomes are death from arrhythmia and total
cardiac mortality within 30 days; secondary outcomes are
all-cause mortality and nonfatal occurrence of ventricular
tachycardia or ventricular fibrillation. A second trial, An-
tiarrhythmic Drugs versus Implantable Defibrillators
(AVID), was begun by the National Institutes of Health
in 1993. The pilot study, involving 200 patients, has been
completed. In the main trial, 1000 patients will be ran-
domly assigned to receive an implantable defibrillator, an
antiarrhythmic drug such as sotalol (with efficacy evalu-
697
 ated invasively or noninvasively), or empiric therapy with
amiodarone. The primary end point is total mortality;
secondary end points are mode of death, quality of life,
and cost-effectiveness.
Recommendations for Use in Patients with Sustained
Ventricular Tachycardia
Currently, conventional antiarrhythmic therapy guided
by electrophysiologic testing or ambulatory monitoring is
usually the first approach to therapy in patients with
sustained ventricular tachyarrhythmia. Options for pa-
tients with arrhythmia refractory to these agents are an
implantable cardioverter-defibrillator or therapy with
amiodarone. Until the final data from CASH and the
results of the AVID and CIDS trials become available, no
data show which approach is associated with the best
outcome. The available data indicate that for the patient
presenting with sustained ventricular tachycardia, amioda-
rone is a reasonable option if other agents are ineffective
or poorly tolerated. Although the drug may not prevent
recurrent ventricular tachycardia, it does often slow the
ventricular rate, making the arrhythmia well tolerated and
not life-threatening. Limited data suggest that this end
point is associated with low mortality, equivalent to that
reported when arrhythmia is no longer induced. For pa-
tients who have a symptomatic or potentially life-threaten-
ing recurrence of ventricular tachycardia despite amioda-
rone, an implantable cardioverter-defibrillator would be
indicated.
When the patient presents with ventricular fibrillation
and conventional agents are ineffective or poorly toler-
ated, the implantable defibrillator is preferred because the
outcome of amiodarone therapy may be more unpredict-
able in such patients. However, for those patients who
have poor left ventricular function and clinical congestive
heart failure, amiodarone may still be a reasonable alter-
native because total cardiac and all-cause mortality rates
appear to be equivalent with these interventions. Of par-
ticular concern are patients who have had a ventricular
tachyarrhythmia but who do not have arrhythmia induced
by electrophysiologic testing or spontaneous ectopy on
ambulatory monitoring. For the patient with intact left
ventricular function and no congestive heart failure, the
implantable defibrillator may be preferred; for the patient
with significant left ventricular dysfunction and congestive
heart failure, amiodarone may be a better option.
Conclusion
Amiodarone is unique among the antiarrhythmic drugs
in many ways. It is highly effective against a wide range of
arrhythmias, and its efficacy appears to be unrelated to
the type and severity of the arrhythmia or to the nature
and extent of underlying heart disease. However, con-
trolled trials are now under way that will provide further
information about amiodarone in different groups of pa-
tients, including those who have recently had myocardial
infarction, those with a cardiomyopathy and nonsustained
ventricular tachycardia, those with atrial fibrillation, and
survivors of sudden death. Amiodarone has not been re-
ported to aggravate arrhythmia or to increase mortality
from sudden death or cardiac mortality in any group of
patients studied to date. Unfortunately, it is associated
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with a wide range of side effects, some of which are
potentially serious, such as liver, thyroid, pulmonary, and
cardiac toxicity. Although many of the minor side effects
are dose-related, serious toxicity is often unrelated to
dose and is unpredictable. However, laboratory abnormal-
ities can serve as markers of potential problems and can
be observed before symptoms develop. Therefore, close
monitoring of chest radiographs, liver and thyroid func-
tion, and cardiac status will often show potentially serious
toxicity early, permitting discontinuation of amiodarone
therapy before any serious symptoms or adverse events
develop.
Requests for Reprints: Philip J. Podrid, MD, Section of Cardiology, Uni-
versity Hospital, 88 East Newton Street, Boston, MA 02118.
Current Author Address: Dr. Podrid: Section of Cardiology, University
Hospital, 88 East Newton Street, Boston, MA 02118.
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