Are All β-Blockers for Heart Failure the Same?

Are All ␤-Blockers for Heart Failure the Same?To the Editor:Kukin et al 1 suggest that little difference may exist between the benefits of metoprolol, a ␤ 1 -selective blocker, and carvedilol, an ␣and nonselective ␤-blocker with antioxidant properties, on pathophysiological variables in patients with heart failure.The study was unblinded and randomized only 67 patients, with more older patients who had advanced symptoms and coronary disease allocated to receive carvedilol.Considerable evidence shows that patients with left ventricular systolic dysfunction due to coronary disease have a more heterogenous improvement in ejection fraction than do patients with dilated cardiomyopathy.2 Moreover, a study that randomized many more (nϭ120) patients showed that when compared with metoprolol, carvedilol had greater effects on ejection fraction and filling pressures.3 No widely accepted surrogates exist for morbidity or mortality in heart failure; therefore, physicians should not assume that a similar hemodynamic benefit leads to equal clinical benefit.The Carvedilol or Metoprolol European Trial (COMET) is currently comparing metoprolol and carvedilol in Ͼ3000 patients with chronic heart failure to determine whether the effects of these drugs on mortality and/or morbidity differ.This is the first adequately powered study to compare outcomes between ␤-blockers in any clinical setting.4 The authors are appropriately and commendably cautious in the interpretation of their data; some commentators are less so. 5 Currently, only carvedilol is approved for use in heart failure.Even if metoprolol is as effective as carvedilol, where is the clinician to get the doses required for initiating therapy?The manual preparation of small quantities of reconstituted low-dose metoprolol is likely to be expensive; the problems of quality control and erratic dosing also exist.It is also inappropriate to assume that substituting maintenance carvedilol with metoprolol is safe.Illicit, large-scale production of generic metoprolol in small doses may occur, but will this be endorsed without proper appraisal by regulatory authorities?Heart failure is a dangerous condition and its treatment with ␤-blockers requires caution.When treating a malignant disease, it seems wise to use treatments that have passed the "acid-test" of official regulatory approval and that are manufactured to an adequate standard.In both the short-and long-term, it may be cheaper and more cost-effective to use carvedilol, which is available in the right doses and with the appropriate pharmaceutical quality control, rather than preparations of ␤-blockers of uncertain strength and efficacy.If heart failure was cancerous rather than merely malignant, what do you think doctors and patients would choose?