Critiques of the COMPANION study that emerged after the release of the results generally did not question its methodology or the validity of its results but focused instead on its generalizability. Numerous editorials proposed eligibility criteria for CRT and ICD. Some authors contended that CRT appropriateness criteria should be extended to include patients with less-severe HF. Others argued that most of the benefit appeared to occur in the most-severe HF patients, and CRT-D use should be restricted to them. Still others suggested that CRT might also benefit patients with narrow QRS HF—or, in other words, patients without obvious conduction delays. Some follow-up analyses attempted to derive predictive factors for the treatment response to CRT. For example, patients with HF from ischemic disease appeared to do less well than those with nonischemic HF. It was also suggested that higher B-type natriuretic peptide (BNP) levels at baseline might predict better outcomes or that functional cardiac MRI to diagnose midwall fibrosis was predictive. Finally, there were questions about cost-effectiveness—estimates ranged from $7,000 to almost $100,000 per QALY saved.
As a group, the three CRT-D trials demonstrated that CRT is appropriate for ICD candidates with severe HF. There was, however, a vigorous debate over the use of the ICD component for primary (not only secondary) prevention of sudden cardiac death in HF patients given both the significantly higher cost of CRT-D over CRT and the marginal gain in outcomes. Estimates of the cost of adding ICD to CRT were as high as $171,538 per additional QALY (Feldman et al., 2005). Thus there were attempts to identify factors that predicted a treatment response from adding ICD to CRT. Some analyses suggested that a wider QRS or worse functional status on the NYHA scale predicted more benefit, while later studies found that these “predictive” factors were only weakly associated and that a broad range of patients benefited from CRT-D rather than CRT alone.