& u published data do not support the use of one particular beta-blocker in low-ejection-fraction CHF, although it is prudent to use agents with which there is published experience. Beta-adrenergic blockers are currently recommended for all but Class IV patients with CHF and low ejection fraction. The recently completed but not yet published (as of this date) COPERNICUS study suggests that beta-blockers are indicated in Class IV patients as well. Until COPERNICUS has been peer reviewed, it is prudent to wait until Class IV patients have improved in clinical class before starting beta-blockers. This does not preclude starting beta-blockers in Class IV patients who are doing poorly on conventional management.

Beta-blocker therapy is initiated at very low doses, with progressive increases approximately every 2 weeks until a target dose is achieved over a period of 2 to 3 months. Symptoms, weight, and physical findings should be carefully monitored during this period. This approach is well tolerated in the vast majority of patients. A small number develop worsening symptoms, usually mild, during initiation of therapy. In most instances, this can be managed by slowing the dose progression and/or increasing diuretics. Beta-blockers should not be considered a form of therapy that will improve clinical class and circulatory congestion on a short-term basis. Indeed, many patients with low ejection fractions will seriously decompensate if these drugs are administered in full beta-blocking doses without gradual dose progression.

There is no evidence that beta-blockers are more or less effective in diabetic patients with low-ejection-fraction CHF than in nondiabetic patients. As with the use of beta-blockers in general, in patients with diabetes the possibility of inducing and/or potentiating hypoglycemia should be kept in mind, but this is mainly an issue in patients who require insulin therapy and have a history of hypoglyce-mia. Other cautions in the use of beta-blockers are identical to those for nondia-betic patients and include adverse conduction system effects, induction of bron-chospasm, and central nervous system side effects.

Spironolactone. The recently published RALES study, a large, controlled clinical trial of spironolactone 25 mg daily in Class III-IV patients with low-ejection-fraction CHF, demonstrated improved survival. The patients recruited for the RALES trial received concomitant conventional therapy with diuretics, digitalis, and ACE inhibitors, but very few received beta-blockers. Accordingly, the potential use of spironolactone in conjunction with beta-blockers was not clarified. Current recommendations are that spironolactone should be administered in addition to conventional therapy to sicker (Class III-IV) patients, whereas beta-blockers should be withheld in Class IV patients. (The COPERNICUS results may modify these recommendations.) This obviously leaves some uncertainty for treatment of Class III patients. Our current practice is to prescribe beta-blockers first in Class III patients and add spironolactone in patients who have had a suboptimal clinical response.

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