Betablocker in der Therapie der chronischen Herzinsuffizienz

Abstract

Once contraindicated, beta-blockers have become an established, evidence-based, recommended treatment concept in chronic heart failure during the last years. The increased activation of the adrenergic system in heart failure syndrome, which leads to transmission of several adverse biological signals to myocytes through adrenergic receptors, provides the rationale for the use of beta-blockers in patients with chronic heart failure. Long-term treatment with different types of beta-blockers addictive to an ACE-inhibitor and diuretics results in normalization of left ventricular shape, an improvement of left ventricular function, and a reduction of hospitalization rate for heart failure. Hemodynamic and clinical improvement is independent of etiology and severity of left ventricular dysfunction. THERAPEUTICAL RECOMMENDATIONS ACCORDINGS TO STUDIES: Adequately powered clinical trials (CIBIS II, MERIT-HF, COPERNICUS) testing different types of beta-blockers (bisoprolol, metoprolol, carvedilol) clearly demonstrated that total mortality and the incidence of sudden cardiac death were significantly reduced in heart failure patients by each of these agents. On the basis of all available evidence, all patients with chronic, stable heart failure (NYHA class II-IV) and with impaired left ventricular function (LVEF < 45%) should receive one of the three above mentioned beta-blockers. Protective effects of beta-blockers in heart failure comprise decrease in heart rate, a decrease of energy consumption, antifibrillatory effects, protection against adrenergic overactivation, and hence, inhibition of myocardial cell necrosis. Moreover, several beta-blockers induce an up-regulation of beta-receptors leading to an improvement of contractility during long-term treatment. It should be mentioned that even a low dosage of beta-blockers exert negative inotropic effects and may lead to a deterioration of hemodynamics and heart failure symptoms in patients with heart failure. The patients treated should be informed that the success of the "paradoxical intervention" will be obvious until 2-3 months after initiation of additional beta-blocker therapy. Beta-blocker treatment for heart failure should be started in stable patients with a very low initial dosage and then up-titrated to the maximal tolerated dosage and should be continued indefinitely. Mortality reduction by beta-blockade in heart failure is no class effect. So far, beneficial effects could only be demonstrated for lipophilic agents. Whether the non-selective beta-blocker carvedilol with additional properties has advantages over the beta-1-selective metoprolol is currently investigated in the COMET (Carvedilol or Metoprolol European Trial) study. Despite the impressive effects in terms of morbidity and mortality reduction, the transfer of these benefits to the clinical practice setting is difficult, with international data showing only 10% of patients with heart failure being treated.