Major β blocker mortality trials in chronic heart failure: a critical review

This review examines, in detail, the three large, published, analyses of the effect of β adrenoceptor antagonist (β blocker) treatment on mortality in patients with chronic heart failure (CHF) caused by left ventricular systolic dysfunction. Two of these reports also describe the effect of treatment on morbidity and this is also reviewed. Lastly, β blocker tolerability, adverse effects, and dosage achieved are also examined. The three mortality reports are compared and contrasted in all these respects and also from the point of view of trial design, inclusion/exclusion criteria, and patients recruited. Conclusions regarding the use of β blockers in patients with CHF, in routine clinical practice, are then drawn from this overview. Comparison of the three mortality reports is somewhat complicated by the fact that one of the reports concerns a pooled analysis of four small studies, individually set up to examine the effect of treatment on non-fatal (mainly symptomatic/exercise tolerance) end points (this was the United States carvedilol programme (USCP)).1-5The other two studies—the second cardiac insufficiency bisoprolol study (CIBIS II) and the metoprolol CR/XL randomised intervention trial in heart failure (MERIT-HF)—were single, prospective, mortality trials.6-9 The USCP also differed from the other two trials in further important ways, including use of a prerandomisation “open label” run-in period and in having a much shorter follow up. All of these features make comparison of the USCP and the other two trials difficult. By contrast, CIBIS II and MERIT-HF are really quite similar in design and outcomes. ### AIM OF STUDY Details of the four trials comprising the USCP are given in tables1-9 and fig 1. Figure 1 Design of the USCP trials in CHF. *Qualifying six minute walk distances modified during study: for severe CHF trial changed to < 350 m; for PRECISE upper limit changed to 450 m; for MOCHA upper …