Pirbuterol, an oral beta-adrenergic receptor agonist, in the treatment of chronic cardiac failure.

Abstract

SUMMARY Pirbuterol (PB), an oral f3-adrenergic-receptor agonist, has the pharmacologic effects of vasodilation and positive inotropy. The present studies were undertaken to determine the value of PB in the long-term therapy of chronic cardiac failure. A double-blind, randomized, 7-week trial comparing PB (20 mg three times daily) with placebo in 12 patients was followed by 12 weeks of open PB therapy. Dosedependent nervousness and tremulousness limited the unit PB dose to < 20 mg in six patients. In all patients, clinical status, exercise tolerance and maximal oxygen uptake, left ventricular echocardiographic dimension and cardiothoracic ratio were unchanged from control after 7 weeks ofplacebo or PB or after 12-19 weeks of PB. To assess the adequacy of 20 mg of PB, the dose-response relations of cardiocirculatory effects to 10, 15, 20 and 30 mg of PB were compared in seven of the above patients and nine other patients. Cardiac output was significantly elevated and wedge pressure reduced after ali four doses, but these changes were sustained for 6 hours after 20-and 30-mg doses only. Thus, the role of PB in the management of chronic cardiac failure appears limited; judgment of its utility must await the results of additional controlled trials.THE PHYSIOLOGIC BASIS for augmenting the performance of the failing heart is rooted in the principles of cardiac muscle mechanics. Muscle fiber shortening, and thereby cardiac output, are enhanced when myocardial contractile state is raised or the load resisting fiber shortening is reduced. i For example, dobutamine is a /31-adrenergic-receptor agonist that augments myocardial contractile state. ' When given intravenously to patients with severe heart failure refractory to standard medical therapy, dobutamine significantly improves ventricular pump function and has therefore proved useful in the short-term treatment of these patients.>9Pharmacologic vasodilation with nitroprusside to attenuate the heightened systemic vascular resistance that accompanies chronic heart failure also raises the output of the failing heart effectively.>4 A theoretically attractive concept for the long-term pharmacologic management of chronic cardiac failure would therefore embrace the principles of augmenting contractility and vasodilation.Pirbuterol is an oral f3-adrenergic-receptor agonist that has positive inotropic and vasodilator properties in dogs.7 In patients with chronic heart failure, Awan et al.8 and Sharma et al.9 found that pirbuterol significantly increased cardiac output while reducing left ventricular filling pressure, and that these salutary hemodynamic effects compared favorably with those of dobutamine.'0 The long-term efficacy and safety of pirbuterol in the management of chronic cardiac fail-

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult

“…The hypothesis underlying this approach suggests that changes in therapy to optimize LV filling pressure may improve outcomes in HF patients (414,415). (435,436), long-term oral therapy with these drugs has not improved symptoms or clinical status (292,(437)(438)(439)(440)(441)(442)(443)(444)(445)(446)(447) and has been associated with a significant increase in mortality, especially in patients with advanced HF (445,(448)(449)(450)(451)(452)(453). Despite these data, some physicians have proposed that the regularly scheduled intermittent use of intravenous positive inotropic drugs (e.g., dobutamine or milrinone) in a supervised outpatient setting might be associated with some clinical benefits (41)(42)(43)454).…”

2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults

“…Although positive inotropic agents can improve cardiac performance during short-and long-term therapy, 185,186 long-term oral therapy with these drugs has not improved symptoms or clinical status 131,[187][188][189][190][191][192][193][194][195][196][197] and has been associated with a significant increase in mortality, especially in patients with advanced HF. 195,198 -203 Despite these data, some physicians have proposed that the regularly scheduled intermittent use of intravenous positive inotropic drugs (e.g., dobutamine or milrinone) in a supervised outpatient setting might be associated with some clinical benefits.…”

Cardiopulmonary Exercise Testing in Clinical Practice

“…Symptomatic maximum Vo, can vary widely since it is quite subjective and has no objective end points. In simply monitoring symptomatic maximum V0, or the duration of treadmill exercise most clinical trials have reported wide variations in effort tolerance, particularly in patients receiving placebo [7], This has not been the case when actual V0 ,max was serially monitored in patients receiving placebo [8], Nevertheless, one could argue that there is a need for a submaximal test with objective end points and that such a test would be more applicable to assess daily living rather than the maximal incremental test. We have explored this issue and found that a submaximal anaerobic ex ercise test may offer such an opportunity [9].…”

“…In using the Vo,max measurement we have found that some drugs have improved a pa tient's effort tolerance [10][11][12] while others have not [8]. In those cases where an im provement in aerobic capacity was noted, this response coincided with the patient's reported enhanced effort tolerance to daily living.…”