To evaluate the role of amiodarone in chronic heart failure.

Literature was scanned using a 'formal, computer-aided search'. No further details were given.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) of amiodarone with objective and reproducible entry criteria were included. Follow-up periods ranged from 6 months to 6 years.

Specific interventions included in the review

Amiodarone in doses ranging from 8 mg/day to 1000mg/day was compared with conventional arrythmic therapy, no therapy and placebo.

Participants included in the review

Patients with the following medical conditions were studied: severe heart failure; post myocardial infarction including those with left ventricular dysfunction; ventricular arrythmia including those at high risk of ventricular fibrillation; and left ventricular dysfunction including those with severe left ventricular failure and those with left ventricular ejection fraction < 35% or < 40%.

Outcomes assessed in the review

Primary outcomes included total mortality, effects of left ventricular function and ventricular arrhythmias. Secondary outcomes included cardiovascular mortality and sudden death.

How were decisions on the relevance of primary studies made?

The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.

The authors do not state that they assessed validity.

Odds ratios (OR) comparing amiodarone with placebo for the end points 'death' and side-effects' were estimated for each study. No details were given of methods used to extract data.

How were the studies combined?

The pooled OR and 95% confidence intervals for outcomes 'mortality' and 'side-effects' were estimated using the Peto fixed-effect model. Other outcomes were subjected to narrative review.

How were differences between studies investigated?

Heterogeneity was tested statistically. Where there was evidence of heterogeneity, random-effects models were fitted and estimates compared with those from fixed-effect models. A continuity correction was used in the random-effects model for outcomes where no events were reported.

Ten RCTs were used to evaluate amiodarone (4306 patients).

Amiodarone resulted in a statistically significant reduction in mortality compared to placebo (8 RCTs). OR = 0.79 (95%CI: 0.68, 0.92; P = 0.003). Reduction in deaths due to amiodarone = 21% (95%CI: 8%, 32%). Heterogeneity P = 0.09. Random-effects model estimated reduction in deaths due to amiodarone = 25% (95% CI: lower limit reported as 5% but this appears to be a misprint), 4%; P = 0.014). Random-effects and fixed-effect models gave similar results.

Amiodarone resulted in a statistically significant increase in side-effects compared to placebo (10 studies. OR = 2.29 (95%CI: 1.97, 2.66; P< 0.001). Heterogeneity P = 0.06. Random-effects model OR = 2.22 (95%CI: 1.83, 2.68). Random-effects and fixed-effect models gave similar results.

Left ventricular function (3 RCTs, 752 patients): the 3 trials all reported statistically significant improvements with amiodarone. Effect size for amiodarone compared to placebo was not given.

Ventricular arrhythmias (3 RCTs, 752 patients): the 3 trials all reported statistically significant improvements with amiodarone. Effect size for amiodarone compared to placebo was not given.

The use of amiodarone in heart failure was associated with an approximate 20% to 25% reduction in deaths. However amiodarone was also associated with a 120% to 124% increase in side effects.

The aims and inclusion criteria were stated. Heterogeneity was assessed statistically and estimates from fixed-effect and random-effects models compared. The discussion included consideration of the following: the effect on efficacy of amiodarone by the drug's potential proarrythmic action; lack of blinding in some trials; differences between trials in patient characteristics (including age, sex, severity of heart failure, and the nature of underlying heart disease); and differences in the incidence of drop-outs, side effects, adherence to therapy, and drug doses.

No details were given of the literature search or of methods used to select primary studies, extract data or test statistical heterogeneity. Without details of the literature search it was not possible to comment on the completeness of the included studies. Validity was not assessed. It was not clear how drop-outs from studies (including those dropping out due to side- effects) were handled. Sensitivity analysis to investigate the effect of different treatments of drop-outs on the stability of results would have been helpful. The above concerns need to be addressed before adequate evidence supporting the authors conclusions could be considered provided.

Practice: The authors consider that no definite answer regarding the role of amiodarone in heart failure is possible at the moment.

Research: The authors consider that further investigation is required into sub-populations who might experience greater benefit (such as those with no-ischaemia or those with more compromised conditions).

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.