ICDs, randomized trials evaluation

Young JB, Abraham WT, Smith AL et al, for the Multicenter Insynch ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators (2003) Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure The MIRACLE ICD Trial. JAMA 289 2719-2721... 

The Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) trial was a randomized, double-blind, parallel-controlled trial of a high-risk population that included patients with left ventricular ejection fraction < 0.35, QRS duration > 130ms and New York Heart Association Functional Class III or IV despite optimal medical beatment. Patients received devices with combined CRT and ICD capabilities and were randomized to the ICD therapy on or off. At 6 months, patients assigned to CRT had a greater improvement in median quality of life score and functional class as compared to controls. No significant differences were observed in changes in left ventricular size or function, overall heart failure status, survival, and rates of hospitalization. No proarrhythmia was observed and arrhythmia termination capabilities were not impaired (82). 

The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a follow-up randomized, double-blind, parallel-conlrolled clinical trial of CRT in New York Heart Association Functional Class II heart failure patients on optimal medical therapy with a left ventricular ejection fraction < 0.35, a QRS > 130ms and a Class I indication for an ICD. Patients were randomized to control group (ICD activated, CRT off) and to CRT group (ICD activated, cardiac-resynchronization therapy on). No significant differences were noted in 6-min walk distance or quality of life scores or peak V02. There were significant improvements in left ventricular diastolic and systolic volumes and in left ventricular ejection fraction (198). 

Pires, L.A., et al.. Clinical predictors and timing of New York Heart Association class improvement with cardiac resynchronization therapy in patients with advanced chronic heart failure results from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) trials. Am Heart J, 2006. 151(4) p. 837-13. 

SCD-HeFT was a prospective, randomized trial that enrolled patients with left ventricular ejection fraction < 0.35 and New York Heart Association Functional Class II-III congestive heart failure to evaluate whether amiodarone or an ICD improved survival compared to a placebo pill. The primary end point of the trial was death from any cause. Amiodarone therapy did not affect outcomes compared to placebo (54). A few studies and one meta-analysis of several large studies have shown reduction in SCD using amiodarone for LV dysfunction due to prior myocardial infarction and nonischemic dilated cardiomyopathy (117,136). Any long-term survival benefit from amiodarone is doubtful. 

Randomized trials can be divided into two types primary prevention trials, in which the ICD is prophylaxis for high-risk patients, and secondary prevention trials, in which the ICD treats sustained ventricular arrhythmias already present. The latter group was more extensively evaluated at first, although... 

Statins may lower mortality in heart failure patients independent of any effects on coronary artery disease. This has been shown through SCD-HeFT data. Statins can also reduce appropriate ICD discharge in few studies including MADIT II post hoc subanalysis (92,115). To date, no randomized controlled trial has evaluated the influence of statins on malignant ventricular arrhythmias or cardiac death independent of the effect on coronary artery disease. 

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