Initiating treatment with the selective beta-blocker, bisoprolol, is as effective and well tolerated as beginning treatment with an ACE inhibitor. However, starting treatment with bisoprolol may reduce the risk of death especially in the first year of treatment.
These findings from the Cardiac Insufficiency BIsoprolol Study III (CIBIS III) challenge the current assumption that treatment of heart failure should begin with an ACE inhibitor subsequently followed by a beta-blocker.
CIBIS III is the first large prospective study to compare the two drug initiation strategies. In newly diagnosed patients over age 65 years (mean age 72 years) treatment was either begun with bisoprolol (n=505 ) or enalapril (n=505). Subsequently, all patients received combination treatment of the two agents. Treatments were titrated to usually recommended doses.
By the end of the study there were no significant differences in either the efficacy or tolerability of the two treatment arms. As a result, one of the principal investigators, Professor Ronnie Willenheimer, Director of Research Unit in the Department of Cardiology at the University Hospital Malmö, Sweden said: "CIBIS III challenges the view that treatment of heart failure patients should be started with an ACE inhibitor rather than a beta-blocker. CIBIS III questions the logic behind such a recommendation."
Evaluating patients after the first year of treatment in a post-hoc analysis, CIBIS III suggests there was a benefit in starting patients on bisoprolol rather than enalapril. In the initial year of treatment, 42 patients in the bisoprolol-first group had died versus 60 deaths in the enalapril-first group; a difference of 31% (p=0.065).
Implications of CIBIS III
Professor Willenheimer said: "Current treatment guidelines recommend that patients with heart failure should begin with an ACE inhibitor, to which a beta-blocker should be added. This strategy has never been tested before in a large, well conducted comparative prospective trial.
"CIBIS III shows that starting treatment with bisoprolol is at least as effective and well tolerated as an ACE inhibitor-first strategy in a population which is typically seen in daily practice (mean age 72 years) over >2 years.
"However, the bisoprolol-first strategy may offer important advantages in the first year of treatment when the risk of sudden cardiac death is particularly high. At this time bisoprolol's pronounced inhibition of the sympathetic system (not seen with an ACE inhibitor) may be of particular value at this critical timepoint when the risk of sudden death is greatest."
Earlier studies show that the first drug initiated in heart failure patients is most likely to be titrated to the full effective dose. Conversely, the second drug may never be fully up-titrated or indeed, never initiated at all.
"We now know from CIBIS III that bisoprolol can be started first as safely as an ACE inhibitor in heart failure patients. And for some, it may have additional benefits that should be considered," Professor Willenheimer concluded.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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