© 2007 European Society of Cardiology
Prescription of beta-blockers in patients with advanced heart failure and preserved left ventricular ejection fraction. Clinical implications and survival
University Medical Centre Groningen, University of Groningen The Netherlands
* Corresponding author. Department of Clinical Pharmacology, University Medical Centre Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. Tel.: +31 0 50 363 6859; fax: +31 0 50 363 2812. E-mail address: d.dobre{at}med.umcg.nl(D. Dobre).
Received July 3, 2007; Dear Sir,
We thank Professor Kjekshus for his comments on our paper [1] and agree that reducing heart rate (HR) with beta-blockers might be one of the mechanisms of action by which these drugs work in heart failure (HF) [2]. He correctly points out, that in patients with coronary artery disease, there is an association between the degree of HR lowering by beta-blockers and the magnitude of survival benefit, and wonders whether we can provide data on HR (and blood pressure response) after treatment.
We agree that this data would have been interesting, but unfortunately no follow-up data on HR (and blood pressure) were available in this observational-cohort of patients, and we are therefore not able to comment on the relation between HR lowering and survival in this population.
The evidence for an association between HR lowering and survival benefit is less clear in HF. Although in CIBIS II, the greatest HR reduction was associated with the largest survival benefit [2], in the larger MERIT-HF trial, no such relation could be observed [3]. Moreover, the presence of atrial fibrillation (AF) in patients with HF may also play a role in this respect. Recently, it was shown that while patients with AF had a similar reduction in HR as those with sinus rhythm at baseline, there was no effect on survival in the AF group [4], and a similar finding was reported in the CIBIS-II trial [2]. Interestingly, as many as 45% of patients had AF in our observational study [1] and it would have been interesting to compare the effects on HR reduction and survival in both patients with AF and in those with sinus rhythm.
Another factor in both survival and reduction of HR in HF is of course the dose of beta-blocker used. In our study, we found that higher doses of beta-blockers exerted a higher benefit than lower doses [1]. Similarly, we recently showed in a post-hoc analysis from the SENIORS study that higher maintenance doses of nebivolol achieved a higher benefit than lower doses, while patients unable to tolerate any dose had the worst prognosis [5]. Only one randomised trial has so far prospectively examined the effect of beta-blocker dose in HF patients, and this MOCHA study [6] showed a dose-related improvement in ejection fraction and survival while no dose-related reduction in HR and blood pressure was associated with the clinical outcome.
In summary, although we generally agree with Professor Kjekshus about HR reduction and survival, this relation is less pronounced in HF, while AF and dose also play a role. More prospective data are needed on this subject.
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- Dobre D., van Veldhuisen D.J., DeJongste M.J., et al. Prescription of beta-blockers in patients with advanced heart failure and preserved left ventricular ejection fraction. Clinical implications and survival. Eur J Heart Fail (2007) 9(3):280–286.
[Abstract/Free Full Text] - Lechat P., Hulot J.S., Escolano S., et al. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. Circulation (2001) 103(10):1428–1433.
[Abstract/Free Full Text] - Wikstrand J., Hjalmarson A., Waagstein F., et al. Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure: analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF). J Am Coll Cardiol (2002) 40(3):491–498.
[Abstract/Free Full Text] - Van Veldhuisen D.J., Aass H., El Allaf D., et al. Presence and development of atrial fibrillation in chronic heart failure. Experiences from the MERIT-HF study. Eur J Heart Fail (2006) 8:539–546.
[Abstract/Free Full Text] - Dobre D., van Veldhuisen D.J., Mordenti G., et al. Tolerability and dose-related effects of nebivolol in elderly patients with heart failure: data from the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (SENIORS) trial. Am Heart J (2007) 154(1):109–115.[CrossRef][Medline]
- Bristow M.R., Gilbert E.M., Abraham W.T., et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation (1996) 94:2807–2816.
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