Effects of beta-adrenergic blockade on survival of patients with chronic heart failure

Observations from experimental studies and controlled clinical trials indicate that prolonged activation of the sympathetic nervous system can accelerate the progression of heart failure, and that the risks of such progression can be substantially decreased through the use of pharmacologic agents that interfere with the actions of the sympathetic nervous system on the heart and peripheral blood vessels. Early studies with β₁-selective agents such as metoprolol and bisoprolol suggested that treatment with β blockers could decrease the risk of worsening heart failure, but showed little or equivocal effects on survival. Recent studies using a more complex nonselective β blocker (e.g., carvedilol) have reported a reduction in mortality as well as in the combined risk of death and hospitalization. This ability to decrease the risk of disease progression led to the recent approval of carvedilol for the treatment of chronic heart failure by the US Food and Drug Administration. However, it is not clear whether these survival effects represent a class effect of β blockers or a specific effect of carvedilol. Carvedilol antagonizes several biologic mechanisms not blocked by metoprolol or bisoprolol that are thought to mediate the progression of heart failure. In additions, in 3 meta-analyses, the survival effects of nonselective vasodilating β blockers appeared to be greater than those of β₁-selective nonvasodilating β blockers. Moreover, it is unknown whether survival benefits can be expected only in the patients who were enrolled in the clinical trials (i.e., New York Heart Association class II or III patients) or whether they can also be achieved in patients with less severe or more severe symptoms (class I or IV heart failure). These questions are being addressed in several ongoing large-scale, long-term survival trials that are scheduled for completion within the next 5 years.