Kathy Faitel

Long‐term Efficacy and Toxicity of High‐ and Low‐Dose Amiodarone Regimens

Amiodarone is an effective antiarrhythmic drug for the control of potentially lethal and lethal ventricular arrhythmias (VA). In the United States, a high‐dose regimen has been used at the expense of a high toxicity profile for the control of lethal VAs. Significant antiarrhythmic efficacy has also been established with low‐dose regimens, which carry a low rate of intolerable side effects (5.4%) when compared with the high‐dose regimen (16.7%). The high incidence of tolerable and intolerable adverse side effects is probably related to high amiodarone loading (31.92 g) and maintenance doses (520 mg/d). In contrast, the low‐dose regimen uses much lower loading (7.2 g) and maintenance (280 mg/d) doses.

Intravenous and oral loading versus oral loading alone with amiodarone for chronic refractory ventricular arrhythmias

To determine whether combined intravenous (i.v.) and oral loading with amiodarone can shorten its onset of action, a comparative study was conducted. Twenty patients with refractory ventricular arrhythmias were treated with amiodarone. All patients had frequent (greater than or equal to 30/hour) and complex (repetitive) ventricular premature beats on a 48-hour baseline Holter recording. Ten patients (group A) received oral loading alone: 800 mg/day for 7 days, 600 mg/day for 3 days, then a maintenance dose 200 to 400 mg/day. Ten patients (group B) received i.v. and oral loading: 5 mg/kg i.v., and then the same regimen as for group A. Follow-up 24-hour Holter recordings were obtained daily for 7 days, weekly for 1 month, and then monthly. Arrhythmia control was defined as at least a 70% reduction in ventricular premature beats, a 90% or greater reduction in couplets and abolition of ventricular tachycardia. The time to optimal ventricular arrhythmia control was shorter for group B (20 +/- 18 vs 105 +/- 83 days, p less than 0.05) and the cumulative amiodarone dose at the time of control was smaller for group B (10 +/- 8 vs 48 +/- 39 g, p less than 0.05). No complications were encountered with i.v. amiodarone. Thus, initial loading with i.v. amiodarone can shorten the time to optimal ventricular arrhythmia control and lower the cumulative dose required.

Arrhythmia control and other factors related to sudden death in coronary disease patients at intermediate risk

Thirty-three patients with coronary artery disease and frequent, complex ventricular arrhythmias (VA) were followed long-term to evaluate factors related to sudden death (SD). Patients with malignant VA (sustained ventricular tachycardia (VT), resuscitated SD, or acute myocardial infarction) were excluded. Baseline data included angiographic ejection fraction (EF), segmental wall motion, and Holter evidence of frequent (greater than 30/hr) and complex (repetitive) ventricular premature beats (VPBs). Control of VA was attempted with conventional or experimental agents and was defined as greater than or equal to 70% reduction in VPBs, greater than or equal to 90% reduction in couplets, and abolition of nonsustained VT on two consecutive Holter tapes. After 24 +/- 15 months of follow-up on the single most effective agent, 18 patients survived while 15 patients died suddenly. There was no difference between these groups with respect to age, sex, or baseline VA. Survivors had a higher EF (51% vs 34%, p less than 0.001), fewer dyskinetic segments (0.05 vs 1.0, p less than 0.01), and better VA control (83% vs 40%, p less than 0.01) than nonsurvivors. By analysis of variance, VA control was not independent of EF (F = 6.98, p less than 0.01). The 1-, 2-, and 3-year survival rates were 90%, 90%, and 82% for patients with EF greater than or equal to 40% and 22%, 11%, and 11%, for those with EF less than 40% and uncontrolled VA.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival of Patients with Nonsustained Ventricular Tachycardia and Impaired Left Ventricular Function Treated with Low‐Dose Amiodarone

C omplex ventricular arrhythmias, especially nonsustained ventricular tachycardia and left ventricular dysfunction, have been associated with an increased risk of sudden death in patients with coronary artery disease1-5 and congestive cardiomyopathy.8 The presence of ventricular arrhythmias reflects the severity of underlying ventricular pathology and dysfunction.9-1#{176} Although the presence of ventricular arrhythmias signals an increased risk of sudden death, the influence of antiarrhythmic therapy on survival is still debated.” Low-dose amiodarone has been shown to be effective in controlling VPCs, and maintaining long-term arrhythmia suppression.12 This drug has been well tolerated in a low-dose regimen12 with minimal negative inotropic effect. This study assessed the effect of low-dose amiodarone on the survival of patients with nonsustained ventricular tachycardia and depressed left ventricular function of less than 40% over 4 years.

Intravenous lorcainide versus lidocaine in the treatment of frequent and complex ventricular arrhythmias

Abstract Thirty patients with frequent (≥30/hr) and repetitive ventricular premature beats (VPBs) unassociated with acute infarction were randomized to intravenous lorcainide (LOR) or lidocaine (LID). Following at least 2 hours of baseline Holter monitoring, patients received LOR, 2 mg/kg then 200 mg/24hr, or LID, 1 mg/kg then 2 mg/min, with rebolus if needed. Nonresponders detected by bedside telemetry were crossed over. Clinical response was 6 of 25 (24%) including two of nine crossovers with LOR and 8 of 26 (31%) including 3 of 12 crossovers with LID ( p = NS). By computer analysis of 24-hour Holter monitors and asymptotic regression of success rates at hourly intervals, it was projected that ≥80% reduction in VPBs occurred in 28% of LOR and in 25% of LID ( p = NS), and complete suppression of repetitive VPBs occurred in 102% of LOR and in 92% of LID ( p = NS). The mean drug levels were 405 ng/ml (range 371 to 463) with LOR and 3.4 μg/ml (range 2.1 to 3.6) with LID. Side effects were similar, occurring in 8 of 25 LOR trials and in 11 of 26 LID trials ( p = NS). Thus, LOR and LID effectively suppress repetitive VPBs and to a lesser extent VPB frequency. However, neither drug is superior and each may be an effective alternative when resistance to the other is encountered.

Efficacy of low-dose amiodarone in the prevention of paroxysmal atrial fibrillation resistant to type IA antiarrhythmic drugs.

&NA; The efficacy and safety of low-dose amiodarone (Cordarone; Wyeth-Ayerst, Philadelphia, PA) was assessed in 62 symptomatic patients with paroxysmal atrial fibrillation who were resistant to at least two types of IA drugs. The beneficial response to this treatment was defined as a reduction in paroxysmal atrial fibrillation of greater than or equal to 50% within 1 month. Of the 42 patients (67.7%) who were responders, 39 (62.9%) were completely free of episodes. Intolerable side effects were seen in 12 patients (19.3%). Tolerable side effects were encountered by 73% of patients. Most of the adverse effects were transient and responded to a reduction in the dose. In conclusion, (1) low-dose amiodarone produces a beneficial response in the prevention of paroxysmal atrial fibrillation, and (2) low-dose amiodarone is well tolerated.

The effectiveness and safety of the simultaneous administration of quinidine and amiodarone in the conversion of chronic atrial fibrillation

The effectiveness and safety of quinidine in the conversion of chronic atrial fibrillation after administration of amiodarone was assessed in 15 patients. A total quinidine dosage of 1097 +/- 408 mg was administered up the point of conversion or for a total of 48 hours. Nine of 15 patients (60%) converted to sinus rhythm. No clinical variable such as the duration of atrial fibrillation, left atrial size, left ventricular fractional shortening, amiodarone duration, or maintenance dose of amiodarone was able to discriminate between converters and nonconverters when patients were treated with the combination of amiodarone and quinidine. The mean QT interval with amiodarone was 414 +/- 44 msec and slightly increased to 434 +/- 40 msec (p = 0.01) when quinidine was added. The amiodarone-quinidine combination was well tolerated, and no side effects or proarrhythmias were recorded.

Is the Degree of Arrhythmia Suppression a Predictor of Survival

The effectiveness of an antiarrhythmic drug is judged by the degree of ventricular arrhythmia (VA) suppression. We evaluated the relationship between the degree of VA suppression and survival in a dose-adjusted trial of 110 symptomatic patients treated with amiodarone. Cohorts had leftventricular ejection fraction (LVEF) of 41 ± 18%, ventricular premature contractions (VPCs) of 445 ± 571 h, couplets (C) of 733 ± 149824 h and nonsustained (N) ventricular tachycardia (VT) of 65 ± 21724 h; these conditions were followed for 15 ± 11.5 months. Amiodarone was initiated with an oral loading of 670 + 111.7 mg per day for 10 days and continued on maintenance of 274.9 ± 102 mg per day. Survival rates of responders and nonresponders with VPCs <70%, 70–89%, >290%; C >90%; NVT (100%); and the response to all 3 criteria (suppression of VPCs >70%, C >90% and complete abolition of NVT) were not statistically significant. Survival rates as a function of LVEF <40% (51 patients) or >40% (59 patients), as well as responders or nonresponders to all three criteria, were not significant (p = NS). We conclude that, in patients treated with low-dose amiodarone, the degree of VA suppression of PVCs, C and NVT does not predict survival; the survival of patients with LVEF <40% improved irrespective of VA suppression; and criteria for VA suppression should be reassessed at lower levels of suppression for the improvement of the drug risk:benefit ratio. More improvement is not necessarily better.