Are the clinical benefits of oral prenalterol in ischaemic heart failure due to beta blockade? A six month randomised double blind comparison with placebo.

Abstract

SUMMARYThe clinical effects of the oral beta, partial agonist, prenalterol, were investigated in 37 patients (29 male, eight female; mean age 57 years) with chronic ischaemic left ventricular failure using a placebo controlled randomised double blind protocol over six months. All patients were limited by dyspnoea (New York Heart Association class III) despite treatment with digoxin and diuretics. Twenty eight patients completed the protocol. Moderate clinical improvement was seen in the prenalterol group, whereas there was little change in the placebo group. Bicycle exercise capacity increased over six months in the prenalterol and placebo groups but only achieved statistical significance for prenalterol when compared with baseline values. Maximum exercise heart rate was significantly reduced in the prenalterol group compared with placebo. Radionuclide left ventricular ejection fraction at rest and during exercise and cardiothoracic ratio showed nosignificant improvement in either group over six months. Prenalterol was well tolerated and produced no increase in frequency of angina or ventricular arrhythmias.Prenalterol produced clinical benefits and improved exercise tolerance while reducing exercise heart rate. A moderate placebo response was noted. The apparent beta blocking effect of prenalterol may be as important as the beta, agonist effect in producing these benefits. Prenalterol has, however, been withdrawn because of side effects in animals.The management of patients with chronic ischaemic left ventricular failure is often difficult and unsatisfactory and usually requires multiple drug treatment.1 The prognosis is poor despite treatment.2 The conventional management is with diuretics and cardiac glycosides,l and, although the role of cardiac glycosides remains controversial,34 recent studies have confirmed that some inotropic support is maintained in patients in sinus rhythm,5-7 especially those with an audible third heart sound.8 In the past decade there has been increasing interest in both vasodilatorRequests for reprints to Dr D R Glover,

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).…”

Heart Failure and Chronic Obstructive Pulmonary Disease

“…All studies involving nebulized or inhaled beta-agonists were included (30)(31)(32). Given the unequivocal results of large randomized controlled trials investigating xamoterol (33,34), we restricted further inclusion of oral beta-agonists to larger studies lasting at least 1 month (35). Medline was searched for "heart failure" and "adrenergic beta-agonists" (n ϭ 374) (33)(34)(35)(36)(37)(38) or "albuterol" (n ϭ 42) (30 -32,39,40) or "terbutaline" (n ϭ 25) (41) or "pirbuterol" (n ϭ 37) (42).…”

“…Although uncommon, ventricular arrhythmias were reported (39). Only 2 studies recruited at least 20 patients and lasted longer than a month (35,42). Although symptoms and exercise tolerance improved, no beta-agonist produced a sustained improvement in systolic function.…”

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.…”