Amiodarone heart failure

The results of MADIT II were met with some skepticism, but later confirmed by the recent Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) [24]. This study evaluated the benefit of ICD therapy versus amiodarone or placebo as primary prevention in over 2,500 patients with stable NYHA class II or III heart failure and EF < 35%, without the requirement for NSVT or EPS. Patients with both ischemic and nonischemic etiologies for cardiomyopathy were included. Over a follow-up of 4 years, there was no benefit of amiodarone over placebo for overall mortality, but ICD therapy resulted in a significant 23% reduction in overall mortality [p = 0.007] (Fig. 3.5). The benefit of ICD therapy was comparable for ischemic and nonischemic cardiomyopathy. 

Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. NEnglJMed. Jan 20 2005 352(3) 225-237. 

Nagele El, Bohlmann M, Eck U, Petersen B, Rodiger W. Combination therapy with carvedilol and amiodarone in patients with severe heart failure. Eur. J. Eleart Fail. 2000 2 71-9. 

Sotalol, as the racemate (a 1 1 mixture of the d- and 1-enantiomers), has a well-documented class Ill-antiarrhythmic activity, without showing the various side-effects of amiodarone. The -adrenoceptor blockade by this agent, however, limits its use in patients with heart failure. Dofetilide is an example of a newer, rather pure class in-antiarrhythmic, virtually devoid of other pharmacological properties. 

Piepoli M, Villani GQ, Ponikowski P, Wright A, Flather MD, Coats AJ. Overview and meta-analysis of randomised trials of amiodarone in chronic heart failure. IntJCard 1998 66(1) 1-10. 

Low doses (100-200 mg/d) of amiodarone are effective in maintaining normal sinus rhythm in patients with atrial fibrillation. The drug is effective in the prevention of recurrent ventricular tachycardia. It is not associated with an increase in mortality in patients with coronary artery disease or heart failure. In many centers, the implanted cardioverter-defibrillator (ICD) has succeeded drug therapy as the primary treatment modality for ventricular tachycardia, but amiodarone may be used for ventricular tachycardia as adjuvant therapy to decrease the frequency of uncomfortable cardioverter-defibrillator discharges. The drug increases the pacing and defibrillation threshold and these devices require retesting after a maintenance dose has been achieved. 

Doval HC, Nul DR, Grancelli HO, Perrone SV Bortman GR, Curiel R, Randomised trial of low-dose amiodarone in severe congestive heart failure, Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA). Lancet 1994 344 493-498. 

Adverse effects Amiodarone shows a variety of toxic effects. After long-term use, more than one half of the patients receiving the drug show side effects sufficiently severe to prompt its discontinuation. Some of the more common effects include interstitial pulmonary fibrosis, gastrointestinal tract intolerance, tremor, ataxia, dizziness, hyper- or hypothyroidism, liver toxicity, photosensitivity, neuropathy, muscle weakness, and blue skin discoloration caused by iodine accumulation in the skin. As noted earlier (see p. 166) recent clinical trials have shown that amiodarone did not reduce incidence of sudden death or prolong survival in patient with congestive heart failure (CHF). 

Medications such as P-blockers, calcium channel blockers, digoxin, and amiodarone can be used to control cardiac conduction abnormalities (arrhythmias), and a pacemaker may be inserted to combat heart failure. The general supportive care measures used in acute stroke syndromes also should be followed. Death in patients with MELAS is usually the result of cardiac failure, pulmonary embolus, or renal failure. 

AMIODARONE BETA-BLOCKERS Risk of bradycardia (occasionally severe), 1 BP and heart failure. Also, t plasma levels of metoprolol Additive negative inotropic and chronotropic effects. In addition, high-dose amiodarone is associated with t plasma levels of metoprolol due to inhibition of CYP2D6 For patients on beta-blockers, monitor BP closely when loading with amiodarone... 

AMIODARONE CALCIUM CHANNEL BLOCKERS Risk of bradycardia, AV block and 1 BP when amiodarone coadministered with diltiazem or verapamil Additive negative inotropic and chronotropic effect. Also, amiodarone inhibits intestinal P-gp, which t the bioavailability of diltiazem and verapamil Monitor PR, BP and ECG closely watch for heart failure... 

Amiodarone and carvedilol have been used in combination in 109 patients with severe heart failure and left ventricular ejection fractions of 0.25 (16). They were given amiodarone 1000 mg/week plus carvedilol titrated to a target dose of 50 mg/day. A dual-chamber pacemaker was inserted and programmed in back-up mode at a basal rate of 40. Significantly more patients were in sinus rhythm after 1 year, and in 47 patients who were studied for at least 1 year the resting heart rate fell from 90 to 59. Ventricular extra beats were suppressed from 1 to 0.1/day and the number of bouts of tachycardia over 167 per minute was reduced from 1.2 to 0.3 episodes per patient per 3 months. The left ventricular ejection fraction increased from 0.26 to 0.39 and New York Heart Association Classification improved from 3.2 to 1.8. The probability of sudden death was significantly reduced by amiodarone plus carvedilol compared with 154 patients treated with amiodarone alone and even more so compared with 283 patients who received no treatment at all. However, the study was not randomized, and this vitiates the results. The main adverse effect was s)mptomatic bradycardia, which occurred in seven patients two of those developed atrioventricular block and four had sinoatrial block and/or sinus bradycardia one patient developed slow atrial fibrillation. 

There have been reviews of the results of major trials of amiodarone after myocardial infarction (35) and in chronic heart failure (36). 

In a meta-analysis of 10 studies of the use of amiodarone in patients with heart failure, the overall odds ratio for mortality with amiodarone compared with placebo was 0.79 (95 % Cl = 0.68, 0.92). The corresponding odds ratio for adverse effects was 2.29 (1.97,2.66) (36). The benefit to risk ratio of the use of amiodarone in these patients is not yet clear. The dosage of amiodarone in these studies varied from 50 to 400 mg/day, with an average of around 250 mg/day. 

The safety and efficacy of amiodarone for supraventricular tachycardia have been studied in 50 infants (mean age 1.0 month, 35 boys) (222). They had congenital heart disease (24%), congestive heart failure (36%), or ventricular dysfunction (44%). Six, who were critically ill, received a loading dose of intravenous amiodarone 5 mg/kg over 1 hour, and all took 20 mg/kg/day orally for 7-10 days, followed by 100 mg/day if this failed to control the dysrhythmia, oral propranolol (2 mg/kg/day) was added. Follow-up was for an average of 16 months. Rhythm control was achieved in aU patients. Growth and... 

The use of intravenous amiodarone for atrial fibrillation has been reviewed (241). The most commonly reported adverse effects in all studies have been hypotension and bradycardia. Qther effects include worsening of heart failure, thrombophlebitis at the site of infusion, non-sustained ventricular tachycardia, facial rash, and nightmares. 

Hofmann R, Wimmer G, Leisch F. Intravenous amiodarone bolus immediately controls heart rate in patients with atrial fibrillation accompanied by severe congestive heart failure. Heart 2000 84(6) 635. 

In patients with heart failure, amiodarone is often required for the treatment of serious ventricular dysrhythmias. The beneficial effects of carvedilol on left ventricular remodeling, systolic function, and symptomatic status were not altered by amiodarone in 80 patients with heart failure. Adverse effects that necessitated withdrawal of carvedilol were no more frequent in patients taking amiodarone than in those taking carvedilol alone (26 versus 25%) (4). 

Macdonald PS, Keogh AM, Aboyoun C, Lund M, Amor R, McCaffrey D. Impact of concurrent amiodarone treatment on the tolerability and efficacy of carvedilol in patients with chronic heart failure. Heart 1999 82(5) 589-93. 

Amiodarone Trials Meta-Analysis Investigators. Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure Meta-analysis of individual data from 6,500 patients in randomized trials. Lancet 1997 350 1417-1424. 

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