Although randomized trials had suggested that ICDs could reduce all-cause mortality, meta-analyses had not been conclusive until the SCD-HeFT results (Sudden Cardiac Death in Heart Failure Trial, paper #10) became available. This trial in 2,521 patients or less showed that the ICD reduced mortality by 23% compared with the drug amiodarone (which itself proved no better than placebo). The benefit was "most obvious in patients with milder symptoms and better functional capacity," Prof. Cleland says, an observation reflecting "both a higher proportion of deaths that are sudden in those with less severe symptoms and that sicker patients are more likely to die of heart failure or other problems." ICDs are not problem-free, he notes. Up to 75% of shocks are unnecessary because the arrhythmia would not have been fatal, and there may be a risk of worsening heart failure too. "ICDs are best deployed in younger (aged under 70 years) and less symptomatic patients with severe persistent left-ventricular dysfunction in whom the risk of dying from things other than sudden death is relatively low, " Cleland says.

Cardiac dyssynchrony means that the normal sequence of activation, contraction, and relaxation is disturbed. Trials had shown that CRT improved symptoms, quality of life, and exercise capacity, but again meta-analysis had not been conclusive for an effect on mortality. The CARE-HF (Cardiac Resynchronization – Heart Failure) trial showed that CRT had a large effect on all-cause mortality, 20% versus 30% in drug-treated controls (J.G. F. Cleland, et al., New Engl. J. Med., 15[352]: 1539-49, 2005; paper #15, total cites 84, latest count 35). Symptom severity did not appear to be a good guide to the long-term benefit from CRT.

What about CRT-D, the device with the two functions? The COMPANION study (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure, #5) found no difference between CRT alone and CRT-D for death from, or hospitalization for, any cause. However, the secondary endpoint of all-cause mortality did suggest an advantage for CRT-D.

A 2005 review (J.C. Daubert, et al., J. Am. Coll. Cardiol., 46[12]: 2204-7, 2005) recommended that prescription of the more expensive CRT-D should be limited to "patients in need of secondary prevention or for younger patients without major comorbidities." Clearly, there is a health-economics argument here, and this is usually explored by comparing treatments in terms of the total costs of achieving one extra quality-adjusted life-year, or QALY. For COMPANION (A.M. Feldman, et al., J. Am. Coll. Cardiol., 46[12]: 2311-21, 2005) the conclusion was that either CRT or CRT-D were cost-effective against the benchmark of $50,000-100,000 per QALY. Cleland tells Science Watch that, from the CARE-HF data (M.J. Calvert, et al., Eur. Heart J., 26[24]: 2681-8, 2005), a CRT-D was cost-effective compared with CRT alone in patients expected to live more than 5-10 years. In his view, "in patients with a low risk of non-cardiac death, for which age is an important surrogate, CRT-D may be the preferred intervention. For patients with advanced symptoms and markers of cardiac dyssynchrony, CRT is indicated almost regardless of prognosis."