Effects of nebivolol on left ventricular function in elderly patients with chronic heart failure: Results of the ENECA study

Medical University of Silesia in Katowice, Catowice, Silesian Voivodeship, Poland
European Journal of Heart Failure (Impact Factor: 6.53). 06/2005; 7(4):631-9. DOI: 10.1016/j.ejheart.2004.10.015
Source: PubMed


To examine the effect of the beta(1)-selective beta-blocker nebivolol, administered as add-on therapy, on left ventricular function in 260 elderly patients (>65 years) with chronic heart failure (CHF).
The principal inclusion criteria were (1) NYHA class II-IV CHF and (2) a left ventricular ejection fraction (LVEF) <= 35%. The primary end-point was the change in LVEF in response to nebivolol treatment for 8 months.
Baseline LVEF values in the two groups were as follows: nebivolol 25.41+/-7.09% and control 26.41+/-5.55%. LVEF improved significantly (p=0.027) more in the nebivolol group (6.51+/-9.15%) than in the control group (3.97+/-9.20%), the relative improvement (percentage increase in the initial value) being 35.70+/-57.62% in the nebivolol group and 19.19+/-40.96% (p=0.008) in the placebo group. Examination of different subgroups did not reveal any heterogeneity in the effects of nebivolol treatment vs. placebo treatment. There were no significant differences between the nebivolol and placebo groups as concerns the changes in clinical status, quality of life, or safety parameters.
The findings of the ENECA study confirmed that nebivolol significantly improved cardiac function and proved to be safe and well tolerated in elderly patients with signs of CHF and an impaired LVEF.

Download full-text


Available from: Istvan Edes, Mar 13, 2015
14 Reads
  • Source
    • "Based on these evidence, two clinical trials have investigated efficacy of nebivolol in aged HF patients. While the ENECA study demonstrated an improvement in LVEF in patients >65 years (Edes et al., 2005), the SENIORS trial showed that nebivolol reduce mortality and hospitalizations by 14% when compared to placebo. Nebivolol was also well tolerated, including in patients with impaired renal function, and the proportion of patients discontinuing treatment due to adverse events was similar in nebivolol and placebo arms (Flather et al., 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The use of β-blockers (BB) in heart failure (HF) has been considered a contradiction for many years. Considering HF simply as a state of inadequate systolic function, BB were contraindicated because of their negative effects on myocardial contractility. Nevertheless, evidence collected in the past years have suggested that additional mechanisms, such as compensatory neuro-humoral hyperactivation or inflammation, could participate in the pathogenesis of this complex disease. Indeed, chronic activation of the sympathetic nervous system, although initially compensating the reduced cardiac output from the failing heart, increases myocardial oxygen demand, ischemia and oxidative stress; moreover, high catecholamine levels induce peripheral vasoconstriction and increase both cardiac pre- and after-load, thus determining additional stress to the cardiac muscle (1). As a consequence of such a different view of the pathogenic mechanisms of HF, the efficacy of BB in the treatment of HF has been investigated in numerous clinical trials. Results from these trials highlighted BB as valid therapeutic tools in HF, providing rational basis for their inclusion in many HF treatment guidelines. However, controversy still exists about their use, in particular with regards to the selection of specific molecules, since BB differ in terms of adrenergic β-receptors selectivity, adjunctive effects on α-receptors, and effects on reactive oxygen species and inflammatory cytokines production. Further concerns about the heterogeneity in the response to BB, as well as the use in specific patients, are matter of debate among clinicians. In this review, we will recapitulate the pharmacological properties and the classification of BB, and the alteration of the adrenergic system occurring during HF that provide a rationale for their use; we will also focus on the possible molecular mechanisms, such as genetic polymorphisms, underlying the different efficacy of molecules belonging to this class.
    Frontiers in Physiology 11/2013; 4:323. DOI:10.3389/fphys.2013.00323 · 3.53 Impact Factor
  • Source
    • "The ENECA study evaluated the effects of nebivolol vs placebo on ventricular remodeling as well as its safety and tolerability, in elderly heart failure patients.40 In this randomized, prospective, multicenter, placebo-controlled, double-blinded, parallel-group study, 260 patients, aged more than 65-years-old (mean age 72-years-old) in NYHA Class II to IV and LVEF ≤ 35%, were randomized to either nebivolol (mean dose 7.2 mg; 64.2% achieved target 10 mg daily) or placebo, as an add-on to usual therapy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Heart failure is a common and disabling condition with morbidity and mortality that increase dramatically with advancing age. Large observational studies, retrospective subgroup analyses and meta-analyses of clinical trials in systolic heart failure, and recently published randomized studies have provided data supporting the use of beta-blockers as a baseline therapy in heart failure in the elderly. Despite the available evidence about beta-blockers, this therapy is still less frequently used in elderly compared to younger patients. Nebivolol is a third-generation cardioselective beta-blocker with L-arginine/nitric oxide-induced vasodilatory properties, approved in Europe and several other countries for the treatment of essential hypertension, and in Europe for the treatment of stable, mild, or moderate chronic heart failure, in addition to standard therapies in elderly patients aged 70 years old or older. The effects of nebivolol on left ventricular function in elderly patients with chronic heart failure (ENECA) and the study of effects of nebivolol intervention on outcomes and rehospitalization in seniors with heart failure (SENIORS) have been specifically aimed to assess the efficacy of beta-blockade in elderly heart failure patients. The results of these two trials demonstrate that nebivolol is well tolerated and effective in reducing mortality and morbidity in older patients, and that the beneficial clinical effect is present also in patients with mildly reduced ejection fraction. Moreover, nebivolol appears to be significantly cost-effective when prescribed in these patients. However, further targeted studies are needed to better define the efficacy as well as safety profile in frail and older patients with comorbid diseases.
    Clinical Interventions in Aging 12/2010; 5:381-93. DOI:10.2147/CIA.S4482 · 2.08 Impact Factor
  • Source
Show more