Beta-blocker treatment for chronic heart failure. The frog prince.

In 1975, Waagstein and colleagues1 published several case reports of patients with heart failure and tachycardia who clinically improved after long-term administration of p-adrenergic antagonists. These initial reports were met with substantial skepticism, since p-blocking agents are negatively inotropic and chronotropic. Their use for treatment of heart failure is counterintuitive and demands considerable clinical acumen and patience to safely institute therapy.2 Thus, on the surface, this therapy is "ugly," much like the frog from the fable of the Frog Prince. Since Waagstein's initial report, the Goteborg collaborators have published several studies on larger patient groups that confirmed their early findings with favorable effects of metoprolol on cardiac function, exercise capacity, and tolerance.3-5 It was reported that institution of long-term P-blockade improved cardiac function and functional class, withdrawal caused deterioration, and reinstitution resulted in improvement.3,5 This group also suggested that chronic P-blockade in patients with idiopathic dilated cardiomyopathy may prolong survival.6 Although this was a small prospective study, a historical control group with matched patients was used, and this was a significant limitation. Twenty-two randomized trials involving 1679 patients have been performed to examine changes in ventricular function, functional status, morbidity, and mortality when p-adrenergic blockade is given to patients with congestive heart failure.2'7-28 In addition, ongoing but as yet unanalyzed studies with carvedilol have involved more than 700 patients. Thus, P-blockers have been administered safely to more than 2300 patients with heart failure. Although some of these trials are small, there is remarkable consistency between trials.