Effect on mode of death of heart failure treatment started with bisoprolol followed by Enalapril, compared to the opposite order: results of the randomized CIBIS III trial.
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.
['Krum|Henry|H|', 'van Veldhuisen|Dirk J|DJ|', 'Funck-Brentano|Christian|C|', 'Vanoli|Emilio|E|', 'Silke|Bernard|B|', 'Erdmann|Erland|E|', 'Follath|Ferenc|F|', 'Ponikowski|Piotr|P|', 'Goulder|Michael|M|', 'Meyer|Wilfried|W|', 'Lechat|Philippe|P|', 'Willenheimer|Ronnie|R|', '|||']
D000319:Adrenergic beta-Antagonists D000368:Aged D000806:Angiotensin-Converting Enzyme Inhibitors D017298:Bisoprolol D002908:Chronic Disease D016757:Death, Sudden, Cardiac D004359:Drug Therapy, Combination D004656:Enalapril D005260:Female D006333:Heart Failure D006760:Hospitalization D006801:Humans D008297:Male
Heart failure Sudden death Adrenergic β-antagonists Angiotensin-converting enzyme inhibitors Drugs