Beta-adrenergic blockers are generally considered to be contraindicated in patients with heart failure because of their negative inotropic effect. Sympathetic activation, however, is associated with an adverse prognosis in patients with heart failure. This observation has led to studies of the role of beta blockers in this population. Haim and associates evaluated the long-term effects of beta-blocker therapy in patients with coronary artery disease and heart failure in New York Heart Association (NYHA) functional classes II and III (see the accompanying table).

Using a population from the registry for a trial of the lipid-lowering agent bezafibrate, the authors compared a group of 1,109 patients in NYHA classes II and III who were receiving beta-blocker therapy at the time of enrollment with a group of 2,116 patients in NYHA classes II and III who were not receiving beta blockers. The beta-blocker dosages were not recorded.

The four-year mortality rate in the patients treated with beta blockers was 9 percent, significantly lower than the 17 percent mortality rate in patients not receiving beta blockers. The cardiac mortality rate was 5 percent in patients treated with beta blockers, compared with a rate of 11 percent in patients not receiving beta blockers. Multivariate analysis revealed that the lower mortality risk associated with beta blockers remained highly significant after adjusting for concomitant therapy with digoxin, diuretics, nitrates or angiotensin converting enzyme (ACE) inhibitors. The lower mortality rates were significant regardless of the patient's sex, history of previous myocardial infarction or NYHA class (II or III).

The authors conclude that patients with ischemic heart failure (NYHA functional classes II and III) who were treated with beta blockers had a 38 percent lower risk for all-cause mortality and a 39 percent lower risk for cardiac mortality than their counterparts who were not treated with beta blockers.

editor's note: The deterioration of cardiac function that occurs with heart failure is secondary to compensatory mechanisms, including neurohormonal activation involving the sympathetic nervous system and the renin-angiotensin-aldosterone hormonal axis. Such protracted alterations lead to ventricular dilatation, increased myocardial energy demand, impaired diastolic function, systemic vasoconstriction, arrhythmias and heart failure. Halting these events with ACE inhibitors slows the progression of heart failure. Beta-adrenergic blockers may do the same, as well as exert antiarrhythmic effects.

Compared with first-generation beta blockers, second-generation agents selective for beta₁ receptors, which include metoprolol, atenolol, bisoprolol and betaxolol, are not as likely to produce systemic vasoconstriction. Thus, they may be of benefit in patients with heart failure when they are used in combination with ACE inhibitors. Third-generation beta blockers, which include carvedilol, labe-tolol, pindolol and sotalol, may have even better myocardial protective properties. Slow titration of beta-blocker therapy is important in these patients, and symptomatic improvement, possibly preceded by a period of decompensation, may require up to three months. It is becoming clear that selected beta blockers can be used in combination with ACE inhibitors in the treatment of mild to moderate heart failure. This approach may delay progression of heart failure and improve survival.—r.s.