Key result
Initiating heart failure therapy with bisoprolol compared to enalapril reduced sudden death at 1 year (HR 0.54; 95% CI 0.29-1.00; P=0.049), though this was offset by increased pump failure deaths.
Why the study?
Does initiating treatment with bisoprolol followed by enalapril reduce sudden death compared to enalapril followed by bisoprolol in patients with mild to moderate stable CHF and LVEF ≤35%?
RCT (n=1,010)
Blinded
Randomized
Does initiating treatment with bisoprolol followed by enalapril reduce sudden death compared to enalapril followed by bisoprolol in patients with mild to moderate stable CHF and LVEF ≤35%?
Hazard Ratio: 0.84 (95% CI 0.51–1.38)
p-value: p=0.487
Initiating heart failure therapy with bisoprolol rather than enalapril may reduce sudden death in the first year, though it may be offset by an increase in pump failure deaths.
Bisoprolol-first initiation may reduce early sudden death in stable HFrEF; extends sequencing data but highlights pump failure offset.
BACKGROUND: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. METHODS: We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. RESULTS: During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events. CONCLUSION: Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort.
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Krum et al. (2010) conducted an RCT in Chronic heart failure (n=1,010). Bisoprolol followed by enalapril vs. Enalapril followed by bisoprolol was evaluated on Sudden death at study end (HR 0.84, 95% CI 0.51-1.38, p=0.487). Initiating heart failure therapy with bisoprolol compared to enalapril reduced sudden death at 1 year (HR 0.54; 95% CI 0.29-1.00; P=0.049), though this was offset by increased pump failure deaths.
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