AMIODARONE THERAPY FOR LIFE THREATENING OR REFRACTORY CARDIAC ARRHYTHMIAS

Amiodarone was used in 40 patients with life-threatening or refractory tachyarrhythmias. Eighteen patients had recurrent ventricular tachycardia of whom 13 had suffered a cardiac arrest. Control has been excellent or good in 17 of these 18 patients during an average follow-up period of 10 months. A further 22 patients had supraventricular arrhythmias, including three with Wolff-Parkinson-White syndrome and paroxysmal atrial fibrillation. In 20 of these control has been excellent or good. The mean daily maintenance dose of amiodarone was 300 mg for patients with ventricular tachyarrhythmias and 200 mg for those with supraventricular tachyarrhythmias. Side-effects were common and included corneal microdeposits, skin rash and discolouration, alteration in thyroid function, and symptomatic bradycardia. Serious adverse effects were uncommon however and necessitated discontinuation of the drug in only two patients. Amiodarone did not appear to precipitate or exacerbate cardiac failure in any patient although many had severe left ventricular dysfunction. We conclude that amiodarone is effective in the therapy of life-threatening or refractory cardiac arrhythmias.     

High incidence of clinical and subclinical toxicity associated with amiodarone treatment of refractory tachyarrhythmias

Amiodarone has been hailed as the most effective single antiarrhythmic drug for treatment of refractory supraventricular and ventricular arrhythmias. However, questions continue to arise about its long-term potential toxicity and true efficacy rates. We, therefore, reviewed our experience with 78 patients, mean age 59 +/- 14 years, with drug refractory tachyarrhythmias treated with amiodarone. Sixty-two patients were treated for recurrent ventricular tachycardia or ventricular fibrillation, 4 for complex ventricular ectopy and 12 for supraventricular tachyarrhythmias. Patients have been treated for a mean of 9.9 months (range, 1 day to 39.1 months); 34(55%) continued to be successfully treated for ventricular tachycardia/ventricular fibrillation, 2 (50%) for complex ventricular ectopy and 5 (42%) for supraventricular tachyarrhythmias. Amiodarone toxicity was frequent, occurring in 57/72 patients (79%) who were treated for more than one week. Adverse effects led to drug discontinuation in 15 (21%), 3 because of pulmonary toxicity (1 in combination with neuropathy and another with drug-induced hepatitis); 2 because of chemical hepatitis; 1, confusion; 6, neuropathy; 2, arrhythmia exacerbation; 2, symptomatic bradycardia; and 1 because of impotence. Of the 62 ventricular tachycardia/ventricular fibrillation patients who were treated with amiodarone, 8 (13%) expired: 4 died suddenly and 4 from documented ventricular tachycardia during treatment. In contrast, of 16 patients who had discontinued amiodarone because of initial adverse effects or drug failure and were treated with alternative antiarrhythmic medications, 5 (31%) died suddenly. In conclusion, amiodarone appears to be fairly effective in high risk patients with refractory cardiac tachyarrhythmias but results in a rather high incidence of adverse effects in long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term low-dose amiodarone therapy in the management of ventricular and supraventricular tachyarrhythmias: Efficacy and safety

Background: Amiodarone hydrochloride has been in use for two decades for the control of ventricular and supraventricular arrhythmias. Established and emerging evidence indicates that amiodarone has an antiarrhythmic efficacy superior to that of most other drugs. Hypothesis: The study was undertaken to evaluate the efficacy and acceptability of low-dose amiodarone therapy in the long-term management of supraventricular and ventricular tachyarrhythmias. Methods: A total of 124 patients with symptomatic drug-refractory or life-threatening arrhythmias managed with low-dose oral amiodarone therapy over a 10-year period was analyzed retrospectively. Of these, 45 patients (36%) had ventricular arrhythmias, 52 (42%) had atrial arrhythmias, and 27 (22%) had atrioventricular reentry tachycardia. Loading doses of amiodarone 600 mg daily for 1 week were administered for supraventricular arrhythmias and 600–1200 mg daily for 2 weeks for ventricular arrhythmias. Maintenance daily doses were 194 ± 48 and 206 ± 55 mg, respectively. Mean treatment duration was 32 ± 28 months, with 326.3 patient years of therapy. Results: Of 39 patients with sustained ventricular tachyarrhythmias, the actuarial incidence of satisfactory arrhythmia control (absence of sudden cardiac death or nonfatal arrhythmia recurrence) was 78% at 1 year and 71 % at 2 years. Satisfactory control of supraventricular arrhythmias (mean ventricular rate < 100/min with significant symptomatic improvement for sustained atrial arrhythmias and < 1 attack per year for paroxysmal atrial or atrioventricular arrhythmias) was achieved in 73, 65, and 62% of patients at 1, 2, and 3 years, respectively. The cumulative incidence of amiodarone-related adverse effects was 5.8 per 100 patient years, with drug withdrawal required in 12 patients (9.7%). Fifteen patients had thyroid dysfunction, 2 had hepatic toxicity, and 1 developed nonfatal pulmonary fibrosis. Overall, the incidence of successful use of amiodarone (satisfactory arrhythmia control and freedom from side effects) was 67, 59, and 53% at 1, 2, and 3 years, respectively. Conclusions: The results of this study suggest that the efficacy of low-dose amiodarone therapy in the management of serious ventricular and supraventricular arrhythmias would be similar to those achieved with higher doses, but with a much more acceptable side effect profile.     

Studies with aprindine

Aprindine is a very effective antiarrhythmic agent with a narrow therapeutic-toxic ratio. It has been used successfully in treating patients who have both supraventricular and ventricular tachyarrhythmias. Aprindine slows conduction in all cardiac fibers and suppresses digitalis-induced after-depolarizations. Voltage-clamp studies indicate that aprindine, in higher doses, suppresses the slow inward current in frog atria. In the dog subjected to coronary artery occlusion, aprindine may be arrhythmogenic, antiarrhythmic, or have no effect on the development of arrhythmias, depending on the temporal relationship between time of administration and time of occlusion.     

Efficacy and toxicity of amiodarone for the treatment of supraventricular tachyarrhythmias

Amiodarone is an effective agent for all types of supraventricular tachyarrhythmias regardless of mechanism and may, in fact, control a high percentage of supraventricular tachyarrhythmias refractory to conventional antiarrhythmic agents. However, its toxicity should temper enthusiasm for the use of the medication in non-life-threatening arrhythmias. As always, when recommending specific therapies the potential benefit should be weighed in light of the related risk. In patients with life disordering, drug-refractory atrial fibrillation, it seems reasonable to attempt control with amiodarone. Likewise in patients with ectopic atrial tachycardias refractory to conventional agents, this seems reasonable as well. Other and better therapies are available for patients with life-threatening arrhythmias associated with the Wolff-Parkinson-White syndrome. While amiodarone is moderately effective in these patients, the advent of improved surgical techniques and the relatively low risk of an operation make surgery the treatment of choice. The role of IV amiodarone, acutely, in the treatment of supraventricular tachyarrhythmias remains to be defined.     

Antiarrhythmische Therapie mit Amiodaron bei tachykarden Rhythmusst?rungen

Amiodarone (Amio) is currently regarded as the most effective antiarrhythmic drug available for the treatment of patients (pts) with supraventricular and ventricular tachyarrhythmias. The most relevant antiarrhythmic effect of amiodarone is due to its prolongation of cardiac repolarization. Amio has been classified as a class III drug after the Vaughan Williams classification. However, its low rate of proarrhythmic complications (incidence ca. 1%) as compared to other class III drugs is at least in part explained by its multiple actions on different ionic channels and ion currents. Amio is the drug of choice in pts with refractory ventricular fibrillation even after unsuccessful DC defibrillation. Amio is effective acutely and during long-term follow-up in pts with supraventricular tachyarrhythmias, especially in pts with atrial fibrillation and low left ventricular function. Despite excellent clinical results, there are frequent and severe side effects on Amio. Therefore, strict indications for this treatment and continuous check-ups are necessary.     

Amiodarone: an effective alternative for recalcitrant supraventricular and ventricular tachycardias

Amiodarone was used in the treatment of 21 patients with supraventricular or ventricular arrhythmias which were refractory to conventional antiarrhythmic drugs, individually or in combination. Six of seven patients with supraventricular arrhythmias and 12 of 14 with ventricular tachycardia were controlled with amiodarone. Although side effects were common, only one patient was removed from treatment due to pulmonary fibrosis. We conclude that amiodarone is an effective antiarrhythmic drug for refractory ventricular and supraventricular arrhythmias.     

Amiodarone: Pharmacology,Clinical Actions,and Relationships Between Them

Amiodarone Therapy. Amiodarone is a unique compound, with actions of all four antiarrhythmic drug classes. It has been used effectively to treat a broad range of ventricular and supraventricular arrhythmias. As a result of amiodarone's enormous volume of distribution and slow disposition kinetics, gradual accumulation occurs during maintenance dosing, and the drug's clinical action can be produced more rapidly with the use of an early loading period. Similarly, plasma concentrations and effects of amiodarone decrease slowly after drug discontinuation. There is a clinical impression that amiodarone is superior over other agents for a wide variety of arrhythmias, but this remains unproven. Because of uncertainty regarding amiodarone's efficacy compared to alternative therapies, and amiodarone's important potential for causing cardiac, pulmonary, hepatic, central nervous system, ocular, thyroid, and cutaneous adverse effects, amiodarone's precise role in antiarrhythmic therapy remains to be established. (J Cardiovasc Electrophysiol, Vol. 3, pp. 266–280, June 1992)     

Control of refractory life-threatening ventricular tachyarrhythmias by amiodarone

The antiarrhythmic effects and dose-response relationship of amiodarone hydrochloride, 600 to 1200 mg daily, were studied in 22 patients with recurrent life-threatening symptomatic ventricular tachyarrhythmias refractory to two or more conventional antiarrhythmic agents. In all patients the presence of the arrhythmia was confirmed on ECG and/or 24-hour Holter readings. In 10 one or more episodes of cardiac arrest had been documented by ECG. Two patients died prior to initiation or stabilization of therapy; the goal of therapy was attained in all but one patient. Amiodarone abolished all complex premature ventricular contractions (PVCs) and paroxysmal or sustained episodes of ventricular tachycardia (VT) in all 19 remaining patients; In the 15 in whom predrug and serial 24-hour Holter recordings could be obtained and analyzed, the total PVC counts were reduced 90% to 98% by amiodarone. After a mean follow-up of 12 months on chronic amiodarone therapy, there have been no recurrences of VT or ventricular fibrillation and sustained antiarrhythmic response has been confirmed by Holter recordings. One patient died suddenly at home despite complete suppression of PVCs. Amiodarone prolonged the PR (+16.7%; P < 0.05) and QT_c (+22.7%; P < 0.01) intervals without effect on QRS duration. Side effects attributable to the drug were gastrointestinal discomfort, halo vision, proximal muscle weakness, transient elevations of hepatic enzymes, and skin photosensitivity, all being reversible on reduction in dosage which did not compromise antiarrhythmic efficacy. Amiodarone did not aggravate cardiac failure even in patients with low ventricular ejection fractions. This study indicates that amiodarone is an extremely potent and safe agent for the prophylactic control of life-threatening ventricular tachyarrhythmias.     

Amiodarone: clinical trials

Amiodarone is an antiarrhythmic agent commonly used in the treatment of supraventricular and ventricular tachyarrhythmias. This article reviews the results and clinical implications of primary and secondary prevention trials in which amiodarone was used in one of the treatment arms. Key post-myocardial infarction primary prevention trials include the European Myocardial Infarct Amiodarone Trial (EMIAT) and the Canadian Amiodarone Myocardial Infarction Trial (CAMIAT), both of which demonstrated that amiodarone reduced arrhythmic but not overall mortality. In congestive heart failure patients, amiodarone was studied as a primary prevention strategy in two pivotal trials: Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiac en Argentina (GESICA) and Amiodarone in Patients With Congestive Heart Failure and Asymptomatic Ventricular Arrhythmia (CHF-STAT). Amiodarone was associated with a neutral overall survival and a trend toward improved survival in nonischemic cardiomyopathy patients in CHF/STAT and improved survival in GESICA. In post-myocardial infarction patients with nonsustained ventricular tachycardia and a depressed ejection fraction, the Multicenter Automatic Defibrillator Implantation Trial (MADIT) demonstrated that implantable cardioverter-defibrillators (ICD) statistically improved survival compared to the antiarrhythmic drug arm, most of whose patients were taking amiodarone. In patients with histories of sustained ventricular tachycardia or ventricular fibrillation, the Cardiac Arrest Study in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE) trial demonstrated that empiric amiodarone lowered arrhythmic recurrence rates compared to other drugs guided by serial Holter or electrophysiologic studies. However, arrhythmic death rates were high in both treatment arms of the study. Several secondary prevention trials, including the Antiarrhythmics Versus Implantable Defibrillators Study (AVID), the Canadian Implantable Defibrillator Study (CIDS), and the Cardiac Arrest Study Hamburg (CASH), have demonstrated the superiority of ICD therapy compared to empiric amiodarone in improving overall survival. Based on the above findings, amiodarone is safe to use in post-myocardial infarction and congestive heart failure patients that need antiarrhythmic therapy. Although amiodarone is effective in treating malignant arrhythmias, high-risk patients should be considered for an ICD as frontline therapy.     

Control of tachyarrhythmias associated with Wolff-Parkinson-White syndrome by amiodarone hydrochloride

Amiodarone hydrochloride proved to be highly effective in preventing and treating arrhythmias of the Wolff-Parkinson-White (WPW) syndrome in 11 patients with WPW conduction and recurrent tachyarrhythmias. Paroxysmal supraventricular tachycardia (six patients), atrial fibrillation (four patients) and atrial flutter (one patient) were the most significant arrhythmias. In most patients the arrhythmia was seriously disabling because of the extremely rapid ventricular rate, adverse hemodynamic consequences and frequent recurrence and long duration of the episodes. Other known antiarrhythmic agents were ineffective. In all 11 patients amiodarone, in doses of 300 to 600 mg daily, totally, easily and safety controlled the arrhythmias for periods of 2 to 8 months. The drug was fully effective after an average of 7 days of treatment. Tolerance to amiodarone was excellent. The occurrence of corneal microdeposits of the drug was the only Important undesirable effect, but subjective ocular disturbances were not noted. The microdeposits are reversible, and can be avoided by discontinuing the drug for 7 days every 1 to 2 months. Amiodarone apparently causes a significant prolongation of refractoriness in the normal (A-V node and His-Purkinje system) as well as in the anomalous pathway, thus creating favorable conditions for prevention and Interruption of any reentry mechanism requiring participation of both pathways.     

Aktueller Stellenwert von Amiodaron in der antiarrhythmischen Therapie

Decades after its registration, amiodarone is still regarded as the most effective antiarrhythmic drug available for the treatment of tachyarrhythmias. Amiodarone is classified as a class III antiarrhythmic drug. In addition to the prolongation of cardiac repolarization, its leading pharmacologic features are sodium and calcium channel block, nonselective β-adrenergic inhibition as well as high lipophilicity and a very long plasma half-life. In patients with paroxysmal atrial fibrillation, amiodarone is the most effective antiarrhythmic drug in maintaining sinus rhythm. Furthermore, it prevents ventricular arrhythmias, such as frequent ventricular extrasystoles or nonsustained runs of ventricular tachycardia, as well as sustained ventricular tachycardia and ventricular fibrillation. In patients with increased risk for sudden cardiac death, e.g., with severely depressed left ventricular function, amiodarone is a highly effective and safe antiarrhythmic drug. In addition, amiodarone has been shown to reduce the number of appropriate and inappropriate shocks in patients with an implantable cardioverter-defibrillator. During long-term amiodarone treatment, typical side effects including corneal microdeposits, blue-gray skin discoloration, photosensitivity, hypothyroidism, hyperthyroidism, peripheral neuropathy, optical neuritis and hepatotoxicity accrue. Upon cessation of medication, these are almost always reversible. Irreversible, severe adverse effects, such as pulmonary toxicity, are very rare under the currently used maintenance dose of 200 mg/day. With regard to its side effect profile, an adequate follow-up of patients including laboratory values, lung function tests, and visual acuity is necessary.     

Significance and control of cardiac arrhythmias in patients with congestive cardiac failure

A wide spectrum of ventricular and supraventricular tachyarrhythmias occurs in the setting of congestive cardiac failure. However, the two most clinically significant are atrial fibrillation and ventricular tachycardia and fibrillation.In the past there has been much emphasis on premature ventricular contractions and more recently, on nonsustained ventricular tachycardia. For the most part, these arrhythmias are asymptomatic in heart failure. They are markers of sudden arrhythmic death but their suppression by antiarrhythmic drugs have not resulted in a reduction of total mortality. Two approaches have been used to this end. The first is the use of beta-adrenergic blocking drugs and antiarrhythmic agents such as amiodarone. Beta-blockers have been shown to significantly reduce sudden death as well as total mortality, while the effects of amiodarone have been less decisive. The prospective role of the implantable cardioverter defibrillator (ICD) is undergoing critical evaluation in patients with cardiac failure at high risk for sudden death. The elective role of the ICD is well established as first-line therapy in patients with heart failure resuscitated from sudden death and in those with sustained ventricular tachycardia in conjunction with conventional therapies for cardiac decompensation.The prevalence of atrial fibrillation rises as a function of severity of cardiac failure, but it is also in known that persistent atrial fibrillation with an uncontrolled ventricular response may induce heart failure. Controlled ventricular response may prevent congestive heart failure and improve left ventricular function. The two most common causes of atrial fibrillation in cardiac failure in Europe and America are ischemic heart disease and hypertension, while mitral valve disease remains the prevalent cause elsewhere. The choice of antiarrhythmic drugs for maintaining sinus rhythm is critical in the prevention of heart failure aggravation and proarrhythmic reactions of antiarrhythmic drugs. Amiodarone and dofetilide are most widely used in this context.     

Amiodarone induced pneumonitis and hyperthyroidism: case report

Amiodarone is a highly effective antiarrhythmic agent used in life-threatening ventricular and supraventricular arrhythmias. Its long-term use may however lead to several adverse effects, including corneal deposits, liver and thyroid gland dysfunction, lung lesions, bone marrow injury, skin lesions, or neurological abnormalities. The article presents the case of a 56-year-old man with a history of a stroke, who after a few days of amiodarone therapy for an episode of atrial fibrillation was diagnosed with amiodarone-induced hyperthyroidism and interstitial pulmonary lesions. Clinical and laboratory symptoms of hyperthyroidism and radiographic signs of pulmonary involvement did not occur until several weeks after discontinuation of amiodarone therapy. Differential diagnosis of causes of hyperthyroidism and diseases causing nodular pulmonary lesions did not demonstrate any other pathologies. Empirical antibiotic therapy and administration of thiamazole and high doses of propranolol failed to improve the patient's clinical status. It was not until thiamazole was given in combination with glucocorticosteroids, when a slow relief of hyperthyroidism symptoms and resolution of radiographic pulmonary signs were observed. Based on the presented case, the risk of appearance of 2 serious concomitant adverse effects was demonstrated, even following a short-term amiodarone therapy. This paper also contains an overview of adverse effects which may be encountered during or after therapy with this effective antiarrhythmic agent. It was emphasized how important it is to select patients appropriately, and to monitor potential adverse effects during amiodarone therapy.     

Thyrotoxicosis induced by amiodarone, a new efficient antiarrhythmic drug with high iodine content

Amiodarone is an antiarrhythmic agent with high iodine content. Ten patients treated with amiodarone developed thyrotoxicosis. I131 uptakes were negligible, and TT3 levels low in relation to TT4 levels, and sometimes even normal. Cessation of amiodarone caused thyroid functions to return to normal in one to five months, unrelated to propylthiouracil treatment. Eight of the patients had normal thyroid glands on radioscan or palpation. All patients tested had normal TRH tests. Thyrotoxicosis is a relatively common complication of amiodarone treatment, probably caused by its high iodine content. It is possible in apparently normal thyroid glands, suggesting failure of the homeostatic mechanisms controlling thyroid synthesis and release in these patients. Amiodarone is very efficient in controlling tachyarrhythmias and angina pectoris, situations in which thyrotoxicosis is dangerous. Thyroid function tests should therefore be drawn periodically, and the complication considered whenever tachyarrhythmias worsen on treatment with amiodarone.     

Herzrhythmusstörungen bei Schwangeren

Maternal cardiac arrhythmias are frequently observed during pregnancy and they can range from benign, clinically-irrelevant isolated premature beats to debilitating supraventricular and ventricular tachycardia. However, malignant ventricular tachyarrhythmias, such as sustained ventricular tachycardia, ventricular flutter and ventricular fibrillation, are relatively rare particularly in women without the presence of an organic heart disease. With regard to the management of arrhythmias during pregnancy, the presence of the foetus and the risk of teratogenicity, the hemodynamic changes under antiarrhythmic drugs, the effects of therapy on labour, delivery and lactation must be taken into account. Although no drug is completely safe, some antiarrhythmic agents such as β ₁-selective β-blockers or digoxin have been tested during pregnancy and have proved to be safe and well-tolerated. Therefore, these drugs can be given with relatively low risk and should be used as first-line whenever possible. In general, drug therapy should be avoided during the first trimester of pregnancy. For supraventricular tachycardia, intravenous adenosine may be used to terminate the arrhythmias if vagal manoeuvres fail because it is an endogenous nucleoside, its half-life is very short and, since the passage through the placenta is reduced by rapid excretion it does not affect foetal hemodynamics. When drug therapy is unsuccessful or not indicated because of the hemodynamic instability of the patient, direct current cardioversion should be used. In hemodynamically instable pregnant patients with malignant sustained ventricular tachyarrhythmias, electrical cardioversion is necessary. Antiarrhythmic drug therapy with β-blockers, ajmaline or antiarrhythmic agent of class IC may be attempted. In case of life-threatening ventricular tachyarrhythmias resistant to other antiarrhythmic drugs amiodarone is recommended and the implantation of a cardioverter-defibrillator has to be discussed. In patients with symptomatic bradycardia, a pacemaker can be implanted at any stage of the pregnancy under echocardiographic guidance.     

The effectiveness of amiodarone seems to depend highly on the pathology underlying the arrhythmia

STUDY OBJECTIVE: To evaluate the efficacy of amiodarone in tachyarrhythmias occurring acutely, in patients with different nosological entities of the heart. DESIGN: A retrospective study. SETTING: Emergency-room patients and ward-patients, in an Internal Medicine Department of a University Hospital. PATIENTS: Sequential sample of 148 patients with acute tachyarrhythmias, 138 out of them supraventricular (atrial fibrillation--116 cases; paraoxysmal supraventricular tachycardia--14 cases, and atrial flutter--8 cases). INTERVENTIONS: 81 patients had been treated with amiodarone; 67 patients had received several other antiarrhythmic drugs. MEASUREMENTS AND MAIN RESULTS: A favourable result of antiarrhythmic treatment was achieved in 84% of the patients who received amiodarone and in only 57% of those having been treated with the other antiarrhythmic drugs (p less than 0.025). A clearly distinct benefit of amiodorone was seen in the subgroup of patients with mitral stenosis, when compared with the whole of the other treatments (p less than 0.001). Amiodarone results were also better than the other antiarrhythmic ones in hypertensive patients (p less than 0.05). There was no difference between amiodarone and the remaining compounds in patients suffering from ischaemic heart disease, congestive heart failure and chronic obstructive lung disease. No adverse side effects were verified is this short term treated sequence of patients. CONCLUSIONS: Amiodarone seems, in this study, to be a very effective antiarrhythmic drug for the treatment of supraventricular tachyarrhythmias. Its efficacy was superior in cases where the underlying disease was mitral stenosis or arterial hypertension. So, effectiveness of the compound seems to depend on the nature of the subjacente cardiac disease. The short term tolerability has been excellent. However, the small number of patients studied claims for bigger scaled similar investigations.     

Amiodarone‐induced bone marrow granulomas

Amiodarone hydrochloride, a class III antiarrhythmic agent used to treat supraventricular and ventricular cardiac dysrhythmias. In this report we describe two patients receiving amiodarone for atrial fibrillation who underwent bone marrow biopsies to investigate paraproteinaemia (case 1) or severe thrombocytopenia (case 2). Multiple bone marrow granulomas were found in both patients, without evidence of any other cause. In both patients the granulomas disappeared after amiodarone withdrawal, suggesting a direct association.     

Amiodarone-induced bone marrow granulomas

Amiodarone hydrochloride, a class III antiarrhythmic agent used to treat supraventricular and ventricular cardiac dysrhythmias. In this report we describe two patients receiving amiodarone for atrial fibrillation who underwent bone marrow biopsies to investigate paraproteinaemia (case 1) or severe thrombocytopenia (case 2). Multiple bone marrow granulomas were found in both patients, without evidence of any other cause. In both patients the granulomas disappeared after amiodarone withdrawal, suggesting a direct association.     

Amiodarone: What have we learned from clinical trials?

Amiodarone is an antiarrhythmic agent commonly used in the treatment of supraventricular and ventricular tachyarrhythmias. This paper reviews clinical trials in which amiodarone was used in one of the treatment arms. Key post-myocardial infarction trials include EMIAT and CAMIAT, both of which demonstrated that amiodarone reduced arrhythmic but not overall mortality. In patients with congestive heart failure (CHF), amiodarone was associated with a neutral survival in CHF/STAT and improvement in survival in GESICA. In patients with nonsustained ventricular tachycardia, the MADIT trial demonstrated that therapy with an implantable cardioverter-defibrillator (ICD) improved survival compared with the antiarrhythmic drug arm in such patients, most of whom were taking amiodarone. In sustained VT/VF patients, the CASCADE trial demonstrated that empiric amiodarone lowered arrhythmic recurrence rates compared with other drugs guided by serial Holter or electrophysiologic studies. Several trials including AVID, CIDS, and CASH have demonstrated the superiority of ICD therapy compared with empiric amiodarone in improving overall survival. Clinical implications of these trials are discussed.